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Osteoporosis has increasingly become a major public health concern because of its associated heightened risk of bone fragility and fractures. In order to avoid the adverse risk of hormone therapy, scientists have considered isoquercitrin (IQ) as a natural phytoestrogen to potentially prevent osteoporosis. However, IQ has poor solubility and bioavailability which culminates in rapid elimination of phytoestrogen. Herein, this study sought to solve limited applications of IQ by preparing IQ-loaded PEGylated long circulating liposomes (IQ-Lips) via thin-film hydration method. After appropriate characterization using zeta-potential, polydispersed index (PDI), particle size and entrapment efficiency (EE), IQ-Lips were applied to ovariectomized rat models to evaluate their effect on osteoporosis. The results showed that the prepared IQ-Lips exhibited smaller sized nanoparticles (125.35 ± 4.50 nm), excellent PDI (0.244 ± 0.001) and zeta-potential (-28.64 ± 0.71 mV) with stable property and higher EE (92.10 ± 0.32%). Importantly, administration of IQ-Lips through oral route increased aqueous solvability, bioavailability and circulation time of IQ. Moreover, the IQ-Lips could increase bone microstructural densities and bone mass, as well as reduce oxidative stress in ovariectomized rat models. Altogether, the IQ-Lips may serve as a novel avenue to potentially prolong the circulation of IQ in the body and improve the bioavailability of IQ for treatment of osteoporosis., Competing Interests: Declarations. Competing Interest: The authors declare no conflict of interest., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Chronic osteomyelitis presents significant treatment challenges, necessitating an efficient system for infection elimination and bone repair. This study developed a natural hydrogel scaffold using silk fibroin (SF) and chitosan thiourea (CST), incorporating vancomycin (VC) and quercetin (QC) loaded PLGA nanoparticles (NPs) for dual-purpose treatment. SF/CST hydrogel scaffolds exhibited homogeneous porosity and smaller interconnected pore size than pure SF and pure CST hydrogel scaffolds. Optimal PLGA/QC NPs measured 206 nm in size, displayed spherical morphology, had uniform distribution, and achieved 87 % QC loading. The release study showed sustained long-term release of VC and QC from the hydrogel scaffolds for over 20 days. Biocompatibility tests indicated that hydrogel scaffolds promoted osteoblast adhesion without cytotoxicity, with QC-containing scaffolds enhancing osteoblast growth. Antibacterial tests confirmed retained VC activity against methicillin-resistant Staphylococcus aureus (MRSA) in SF/CST. An experimental study assessed the efficacy of the hydrogel scaffolds in a MRSA-infected rat osteomyelitis model. Radiographic scores demonstrated a significant reduction for SF/CST-VC-PLGA/QC NPs compared to control, indicating reduced osteomyelitis effects. Macroscopic evaluations showed notable reductions in gross pathological effects for VC-containing groups. Histopathological assessments revealed significantly lower osteomyelitis scores and higher healing scores in the SF/CST-VC-PLGA/QC NPs, with reduced inflammatory cell infiltration and more organized connective tissue formation. In conclusion, SF/CST-VC-PLGA/QC NPs is an effective dual drug delivery system for osteomyelitis treatment, demonstrating significant antibacterial activity, enhanced bone regeneration, and reduced infection rate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Dihydroquercetin is a natural flavonoid with anti-inflammatory, antioxidant, and neuroprotective activities. Dihydroquercetin exhibits a great neuroprotector promise in Alzheimer's disorder via preventing the aggregation of amyloid-beta-peptide-Aβ(1-42). The goal of the study was to create dihydroquercetin-loaded-chitosan nanoparticles (DHQ-CS NPs) loaded to a mucoadhesive, thermosensitive in-situ gel for direct nasal administration to cure Alzheimer's disorder. Loading drug in chitosan nanoparticles and incorporation into thermosensitive gel enhanced residence time and reduced mucociliary-clearance. Different in-vitro-physicochemical-characteristics of gels and nanoparticles-characterization were used to evaluate the formulations. The therapeutic effectiveness of DHQ-CS NPs gel was evaluated behaviorally, biochemically and histopathologically in Alzheimer's-rat-model compared to intranasal DHQ gel. The small particles-size was obtained = 235.3 nm of DHQ-CS NPs. The DHQ-CS NPs gel demonstrated a greater release rate compared to the raw DHQ gel. Additionally, the nasal-administration of the DHQ-CS NPs gel showed better In-vivo results compared to DHQ gel, through improvement of memory and learning deficits and also the exploratory behavior and new object memory in streptozotocin induced-Alzheimer rats. Biochemically, the intranasal DHQ-CS NPs gel, showed reduced both Aβ-protein formation and tau protein hyperphosphorylation, inhibition of acetylcholine esterase activity and oxidative stress in the brain with increase of total antioxidants in the brain and serum, compared to DHQ gel. Histopathologically, the DHQ-CS NPs nasal gel produced improvement in the hippocampal and cerebral cortex structures, being comparable to the normal group. Consequently, the intranasal DHQ-CS NPs loaded in-situ gel seems to be a promising therapeutic formulation for Alzheimer's disease medication., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Poor water solubility and low bioavailability of flavonoids present significant barriers to their development and application. To address these challenges, this study explores the use of crystalline solid dispersions (CSDs) to reduce drug crystalline size and enhance in vivo bioavailability. The CSDs were prepared using a spray-drying technique with chrysin (CHY) and quercetin (QUR) as model drugs and various molecular weights of polyethylene glycol (PEG) as carriers. The authors systematically investigated the factors influencing the interaction between flavonoids and PEG in CSDs. These factors included the relationships between intermolecular interactions and PEG molecular weight, crystallinity, microstructures such as crystalline domain size and crystal morphology of the flavonoids and PEG in CSDs, crystalline size of the drug in CSDs, and in vitro dissolution rate and in vivo pharmacokinetics. Our results indicated that the interaction between flavonoids and PEG in CSDs was influenced more by PEG crystallinity than by its molecular weight. Lower crystallinity of PEG, achieved through recrystallization, led to stronger intermolecular interactions with the drugs. Specifically, PEG8000 exhibited the lowest crystallinity, indicating a higher content of PEG in the amorphous state, which interacted more effectively with the amorphous drug in CSDs. This interaction significantly inhibited drug crystallization growth, resulting in a marked decrease in drug crystalline domain size and crystalline size. Consequently, PEG8000 was identified as the optimal carrier for preparing CSDs, achieving the best cumulative dissolution percentage. The QUR/PEG8000-CSD formulation increased the cumulative dissolution percentage and oral bioavailability of QUR by 18.76 and 20.66 times, respectively, compared to QUR alone. This study demonstrates that PEG crystallinity, following recrystallization, directly affects its intermolecular interactions with the drug, thereby impacting drug crystalline size and dissolution rate., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: There is growing interest in the use of nutrition and dietary supplements to optimize training and time-trial (TT) performance in cyclists. Separately, quercetin (QCT) and citrulline (CIT) have been used as ergogenic aids to improve oxygen (VO 2 ) kinetics, perceived effort, and cycling TT performance. However, whether the combination of QCT and CIT can provide additive benefits and further enhance cycling performance production is currently unknown., Methods: We examined 28-days of QCT + CIT supplementation on TT performance and several performance measures (i.e. mean power, VO 2 , respiratory exchange ratio (RER), and rate of perceived exertion (RPE)). Forty-eight highly trained cyclists were assigned to one of four supplementation groups: (1) QCT + CIT (QCT: 500 mg, CIT: 3000 g), (2) QCT (500 mg), (3) CIT (3000 mg), or (4) placebo (3500 mg of a zero-calorie flavored crystal light package). Supplements were consumed two times per day for 28 consecutive days. Participants performed a 20-km cycling time-trial race, pre- and post-supplementation to determine the impact of the combined effects of QCT + CIT., Results: There were no potential benefits of QCT +CIT supplementation on TT performance and several performance measures. However, there was an improvement in VO 2 from pre-to-post-supplementation in QCT ( p  = 0.05) and CIT ( p  = 0.04) groups, but not in the QCT+CIT and PL groups., Conclusions: QCT + CIT does not seem beneficial for 20-km TT performance; further exploration with a focus on an increase in cycling duration or QCT+CIT combined with additional polyphenols may amplify any perceived bioactive or metabolic effects on cycling performance. The efficacy of QCT + CIT supplementation to improve cycling performance remains ambiguous.

Background: The long history of clinical experience in China have confirmed the effectiveness of traditional Chinese medicine (TCM) in treating prostate cancer (PCa). Until now, several bioactive compounds with anti-PCa potential, such as curcumin, gallic acid, and quercetin, have been extracted from TCM. Recent studies have shown that encapsulating these TCM bioactive compounds into nano-delivery system enhanced their bioavailability and improved their ability to target PCa tumors., Purpose: This review aims to summarize the anti-PCa effects and molecular mechanisms of TCM bioactive compounds and discuss the clinical application prospects and future research trends of nano-delivery system based on these compounds., Methods: Literatures focusing on the treatment of PCa using traditional Chinese medicine compounds via nano-drug delivery system were searched from Electronic databases, including PubMed, Web of Science, and Scopus until December 2023., Results: Polyphenols, alkaloids, terpenes, and quinones exhibit anti-PCa effects through various pathways. Notably, compounds like curcumin, gallic acid, quercetin, and tanshinone have been extensively studied in nano-delivery systems for anti-PCa purpose. Nano-delivery systems enhance the biological activity of free compounds and reduce toxic side effects, as well. Commonly used nanomaterials for delivering TCM compounds include polymer nanomaterials, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and niosomes., Conclusion: Research on nano-delivery systems for TCM bioactive compounds holds promising prospects for anti-PCa therapy. However, extensive clinical trials are necessary to evaluate the effectiveness and safety of these nanodrugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: The aim of this study was to investigate the protective effect of quercetin loaded on solid lipid nanoparticles (SLN) in protecting human hair from ultraviolet-B (UV-B) light in vitro., Methods: In this study, solvent-emulsified diffusion method was used to fabricate nanoparticle formulations and then particle size, loading, and drug release tests were performed from different formulations. Variables include oily part proportion, liquid to solid oil part ratio, and surfactant to lipid ratio. The optimal formulation was prepared by examining the eight formulations and optimizing them. Six groups of hair with different treatments were exposed to UV light for 600 h and the changes were investigated by examining four factors: RMS (root mean square average, the microscopic profile peaks and valleys), peak to valley roughness, the amount of chemical changes by Fourier transform infrared spectroscopy (FTIR), and the amount of protein loss., Results: The selected formulation had a suitable particle size, loading percent, and release rate for penetration to hair. Quercetin-loaded SLN controlled RMS factor, peak to valley roughness, and reduced chemical changes and protein loss compared to other treatments., Conclusion: The optimize formulation showed positive effects in protecting the hair strands from UV-B radiation., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

The current investigation was designed as an experimental endeavor to explore the protective efficacy of dehydroepiandrosterone (DHEA) and quercetin against hepatotoxicity induced by copper oxide (CuO) nanoparticles. Rats were subjected to CuO nanoparticle intoxication through intraperitoneal injection of 150 mg/kg b.w. for three weeks, followed by the administration of the aforementioned antioxidants for an additional three weeks. This study systematically tracked alterations in liver enzymatic activity, antioxidant levels, apoptotic markers, and histopathological changes using the comet assay. CuO nanoparticle-intoxicated rats exhibited a significant increase in serum alanine transaminase aspartate aminotransferase (AST), and bilirubin levels, coupled with a noteworthy reduction in serum albumin. Moreover, there was a marked rise in serum tumor necrosis factor-alpha levels, concomitant with a significant decline in serum hepatocyte growth factor (HGF). Caspase-3 and Bax mRNA levels in the serum showed a substantial increase, while serum Bcl-2 mRNA levels witnessed a significant decrease. Liver tissue levels of malondialdehyde (MDA) and nitric oxide (NOx) experienced a significant elevation, and DNA damage was observed through the comet assay. Histopathological examination of the liver tissue substantiated these aforementioned findings. Administration of the antioxidants DHEA or quercetin, either individually or in combination, mitigated the parameters of hepatotoxicity to varying extents. In summary, the hepatic genotoxicity induced by CuO nanoparticles demonstrated improvement following the administration of either DHEA or quercetin. Additionally, their combined administration exhibited a more potent protective potential., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: The Research and Ethics Committee, College of Medicine, Immam Abdulrahman University, Kingdom of Suadi Arabia approved the study protocol (IRB-2021–93-1)., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Nanoparticle (NP)-based drug delivery systems have caused a paradigm shift in cancer treatment by enabling drug targeting, sustaining drug release, and reducing systemic toxicity of chemotherapy. Here we developed a novel NP formulation for the anticancer drug mitoxantrone (MTZ) by loading it into an emerging nanomaterial derived from the plant polyphenol quercetin (QCT). QCT was partially oxidized to produce amphiphilic oxQCT which was co-assembled with poly(ethylene glycol) (PEG) and MTZ by nanoprecipitation to form MTZ NPs. The optimal NPs exhibited an average diameter of 128 nm, a polydispersity index of 0.22, and a drug loading efficiency of 76%. While only a small fraction of the loaded drug was released at physiologic pH, a significantly higher fraction was released at acidic pH. The anticancer activity of MTZ NPs was assessed in MCF-7 and MDA-MB-231 breast cancer cell lines, alone and in combination with the bioactive natural products curcumin (CUR) and thymoquinone (TQ). In cell viability assays, MTZ NPs were slightly less potent than free MTZ, most likely due to their sustained release properties, but their cytotoxicity was greatly enhanced in the presence of TQ (in MCF-7 cells) as well as CUR (in MDA-MB-231 cells). The results were corroborated by apoptosis assays such as mitochondrial membrane potential measurement, acridine orange/ethidium bromide staining, in addition to caspase activity assays. The assays revealed that the NPs' proapoptotic effect was enhanced in the presence of CUR or TQ, depending on the cell line. Our work presents a promising nanocarrier platform for MTZ with the potential to enhance its bioactivity against breast cancer when combined with bioactive natural products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Moisture loss, infection, and severe inflammatory reactions are the primary factors affecting burn wound healing and leading to scar formation. Herein, we developed a quercetin-loaded polysaccharide-based injectable hydrogel (named PECE). The PECE consists of oxidized sodium alginate (OAlg) coupled with chitosan (CS) via Schiff bases and electrostatic interactions, while Que is incorporated via hydrogen bonding. Benefiting from the hydroxyl and carboxyl groups, PECE features distinguished moisturizing ability. Additionally, the sustained release of Que imparts remarkable antibacterial activity against Escherichia coli and Staphylococcus aureus . Likewise, PECE demonstrates favorable in vitro anti-inflammatory capacity as released Que significantly downregulates pro-inflammatory factors (IL-6 and TNF-α) secreted by RAW 264.7 macrophages. More importantly, in a rat model of deep second-degree burn wounds, PECE effectively inhibits wound infection, reduces inflammation, and promotes angiogenesis and collagen deposition, ultimately minimizing scar formation. Overall, this work presents a promising strategy for scarless healing of burn wounds.

In this study, in order to solve the application problems of poor water solubility and low bioavailability of quercetin, we prepared a nano-delivery system with core-shell structure by anti-solvent method, including a hydrophilic shell composed of tea saponin and a hydrophobic core composed of Zein, which was used to improve the delivery efficiency and biological activity of quercetin. Through the optimal experiments, the loading rate and encapsulation rate of nanoparticles reached 89.41 % and 7.94 % respectively. And the water solubility of quercetin is improved by 30.16 times. At the same time, the quercetin acted with Zein through non-covalent interaction and destroyed its spatial network through structural characterization, while tea saponin covered the surface of Zein through electrostatic interaction, making it change into amorphous state. In addition, the addition of tea saponin makes the nanoparticles remain stable under the changes of external environment. During simulating gastrointestinal digestion procedure, ZQTNPs has higher release rate and bioavailability than free quercetin. Importantly, ZQTNPs can overcome the limitations of a single substance through synergy. These results will promote the innovative development of quercetin precision nutrition delivery system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The present study aimed to examine the protective effect of quercetin (QUE) on cyclophosphamide (CTX)-induced nephrotoxicity. For that purpose, 24 mice were divided into four groups (Control, QUE, CTX, and CTX + QUE). The CTX and CTX + QUE groups received 200 mg/kg of cyclophosphamide on the 1 st and 7 th days. The QUE and CTX + QUE groups were treated with 50 mg/kg of quercetin daily for 14 days. At the end of the experiment, the animals were sacrificed, and kidney samples were analyzed. The results indicated that CTX leads to severe morphological degenerations and disruption in renal function. Serum BUN, Creatinine, Uric acid, tissue Bax, Caspase 3, TNF-α and IL-1β expression levels were upregulated in the CTX group compared to Control and QUE groups ( p  < 0.05). Although MAPK/ERK phosphorylation level is not affected in CTX group, there was a significant increase in CTX + QUE group ( p  < 0.05), but the NF-κB was significantly suppressed in this group ( p  < 0.01). The RT-qPCR results showed that the cyt-c and the Bax/Bcl-2 ratio mRNA expression folds were upregulated in the CTX group ( p  < 0.01), which was downregulated in the CTX + QUE group. However, there was a significant difference in the CTX + QUE group compared to the Control and QUE groups ( p  < 0.01). The findings showed that administering quercetin along with cyclophosphamide alleviated renal injury by regulating apoptotic and inflammatory expression. Moreover, the administration of quercetin and cyclophosphamide could synergistically improve renal function test results, and activate cellular responses, which upmodulate MAPK/ERK phosphorylation and suppression of NF-κB.

Quercetin, as a representative flavonoid, is widely present in daily diet and has been developed as a dietary supplement due to its beneficial physiological activities. However, the application of quercetin is limited due to its poor water solubility and extensive metabolism. So far, the nano-drug delivery systems designed to improve its bioavailability generally have the shortcomings of low drug loading content and difficulty in industrial production. In order to tackle these problems, quercetin supersaturated drug delivery system (QSDDS) was successfully prepared using solvent method, for which PVP K30 was employed as a crystallization and precipitation inhibitor to maintain the supersaturated state of quercetin in aqueous system. The obtained QSDDS, with a relative high drug loading content of 13%, could quickly disperse in water and form colloidal system with the mean particle size of about 200 nm, meanwhile induce the generation of supersaturated quercetin solution more than 12 h. In vivo pharmacokinetic study proved that QSDDS achieved a high absolute bioavailability of 36.05%, 10 times as that of physical quercetin suspension, which was dose-dependent with higher bioavailability at higher dose. Considering the simple preparation method, QSDDS provided a feasible strategy and a simple way to improve oral absorption of insoluble flavonoids., (© 2024. Controlled Release Society.)

Ulcerative colitis (UC) is an inflammatory bowel disease that predominantly impacts the colon, typically starting in the rectum. A significant characteristic of UC is its propensity to affect the distal colon, which is particularly beneficial for targeted treatments such as enemas. This localized approach ensures that the medication is delivered directly to the affected areas, resulting in minimal systemic absorption. In this research, we have formulated a novel stimuli-responsive quercetin-loaded guanosine borate supramolecular hydrogel (named GBQ hydrogel), designed to prolong the residence time of the drug and protect the ulcerated intestinal tissues. The GBQ hydrogel has exhibited excellent injectability, self-healing capabilities, and biocompatibility, rendering it an ideal candidate for enema administration. In vitro studies have highlighted its ROS/pH dual-responsive release profile, which mimics the microenvironment of intestinal inflammation. Furthermore, we assessed the efficacy of the GBQ hydrogel on dextran sulfate sodium (DSS)-induced colitis, a common animal model for UC. Our findings indicate that the GBQ hydrogel significantly reduces disease activity, mitigates oxidative stress, restores the intestinal mucosal barrier, and prevents colonic cell apoptosis. Collectively, this study underscores the therapeutic potential of the GBQ hydrogel in managing inflammatory bowel conditions and paves the way for a novel hydrogel enema-based treatment strategy for UC.

Background: Nutritional interventions with natural antioxidants can provide a pragmatic solution for modifying hens' performance and maintaining oxidative stability of eggs during storage. Quercetin is the most abundant flavonoids with potent antioxidant and immune stimulant activities. The concept of incorporating of quercetin, as potent antioxidant and immunostimulant, into effective nano-carriers (QNPs) has promoted their bioavailability and stability thus, their effectiveness for the first time were assessed on laying hens' performance and immunity, eggs quality during storage. Four hundred 12-weeks-old Hy-line brown laying hens were distributed to four experimental groups: control group fed basal diets, and other 3 groups fed basal diets fortified with 100, 200 and 300 mg/kg QNPs for 60 weeks., Results: Laying performance and quality of laid eggs were improved as expressed by elevated laying rate, egg mass %, eggs weight and yolk weight in QNPs200 and 300. Fortification of QNPs300 remarkably decreased layers serum total cholesterol concurrently with decreased egg yolk saturated fatty acids and cholesterol while increased polyunsaturated fatty acids. Over- 45 days storage period, QNPs enhanced phospholipids, total phenolics and flavonoids, total antioxidant activity (T-AOC) simultaneous with decreased MDA content in eggs. Furthermore, enhanced immune response was detected in both in serum and intestine of QNPs fed hens as reflected by higher lysozymes activity, IgM, IgG and phagocytic index and demotion of NO together with AvBD 6-12, IL-10, IgM and ATg 5-7-12 upregulation and downregulation of IL-1β and TNF-α especially at QNPs200 and 300. Intestinal redox balance was modified via decreasing H 2 O 2 and MDA simultaneous with upregulation of catalase, SOD, GSH-Px, HO-1 and NQO1 in groups fed higher doses of QNPs., Conclusions: QNPs supplementation provides a new nutritional strategy towards increasing hen performance, fortification of eggs with natural antioxidants that prevents egg quality deterioration during storage., (© 2024. The Author(s).)

Co-amorphous (CM) is a promising technology for enhancing the aqueous solubility of insoluble drugs, but the gelation phenomenon has often occurred during the dissolution process and seriously threatened their solubility/dissolution performance. Therefore, it's quite important to design favorable CM systems to alleviate or even avoid the adverse effects of gelation phenomenon. In this study, CM systems of taxifolin (TAX) and oxymatrine (OMT) (TAX-OMT CMs) were constructed to improve the solubility and dissolution properties of TAX. Interestingly, TAX-OMT CMs gradually aggregated and obviously gelled during dissolution, but the solubility and dissolution of TAX in TAX-OMT CMs were significantly enhanced compared to crystalline TAX. Consequently, the underlying solubilization mechanisms of TAX-OMT CMs after gelation were systematically explored. For one thing, the complexation between the two components in TAX-OMT CMs was verified by phase solubility, fluorescence spectroscopy and isothermal titration calorimetry. For another, the residual solids of TAX-OMT CMs after dissolution evaluation were thoroughly characterized by means of powder X-ray diffraction, fourier transform infrared spectroscopy, scanning electron microscopy, which showed the anti-crystallization property of TAX-OMT CMs. Furthermore, molecular simulation demonstrated the intermolecular interactions of TAX-OMT CMs alone and TAX-OMT complexes in aqueous solution. Finally, pharmacokinetics study in rats suggested that the bioavailability of TAX in TAX-OMT CM (1:2) was approximately 5.5-fold higher than that of crystalline TAX after oral administration. Collectively, this study reveals the importance of complexation and anti-crystallization effects of CM systems on maintaining solubilization behavior after gelation, providing an effective strategy to improve the absorption performance of pharmaceutical CM systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gut microbiota provides an important insight into clarifying the mechanism of active substances with low bioavailability, but its specific action mechanism varied case by case and remained unclear. Dihydroquercetin (DHQ) is a bioactive flavonoid with low bioavailability, which showed beneficial effects on colitis alleviation and gut microbiota modulation. Herein, we aimed to explore the microbiota-dependent anticolitis mechanism of DHQ in sight of gut microbiota metabolites and their interactions with microRNAs (miRNAs). Dietary supplementation of DHQ alleviated dextran sulfate sodium-induced colitis phenotypes and improved gut microbiota dysbiosis. Fecal microbiota transplantation further revealed that the anticolitis activity of DHQ was mediated by gut microbiota. To clarify how the modulated gut microbiota alleviated colitis in mice, the tandem analyses of the microbiome and targeted metabolome were performed, and altered profiles of metabolite short-chain fatty acids (SCFAs) and bile acids and their producers were observed in DHQ-treated mice. In addition, SCFA treatment showed anticolitis activity compared to that of bile acids, along with the specific inhibition on the phosphoinositide-3-kinase (PI3K)-protein kinase B (Akt) pathway. Subsequently, the colonic miRNA profile of mice receiving SCFA treatment was sequenced, and a differentially expressed miR-10a-5p was identified. Both prediction analysis and dual-luciferase reporter assay indicated that miR-10a-5p directly bind to the 3'-untranslated regions of gene pik 3 ca , inhibit the PI3K-Akt pathway activation, and lead to colitis alleviation. Together, we proposed that gut microbiota mediated the anticolitis activity of DHQ through the SCFAs/miR-10a-5p/PI3K-Akt axis, and it provided a novel insight into clarifying the microbiota-dependent mechanism via the interaction between metabolites and miRNAs.

In industrialized farms, rabbit does undergo intensive production rhythms which overlap lactation and gestation, leading to a high energy mobilization and increasing oxidative stress. Accordingly, we hypothesize that administration of the flavonoid quercetin (QUR) may improve the antioxidant status of young and adult rabbit reproductive females. In this study, the effect of daily oral administration of 300 mg/kg QUR for 8 weeks was assessed on the antioxidant profile of 24 New Zealand × Californian rabbit does, assigned to 4 experimental groups: rearing young (8-16 weeks old) and adult does at the end of their reproductive life (12-14 months old, with at least 3-4 reproductive cycles) treated (YQ and AQ) or not (YC and AC) with QUR, respectively. Plasma glutathione (GSH), as well as serum superoxide dismutase (SOD) and malondialdehyde (MDA) were measured during the experimental period. To assess the health status of the animals, a physical examination was also performed. GSH plasma concentrations were significantly higher in young does at weeks 1 and 4, but not at week 8 of the experiment, irrespectively of QUR administration. An increase in GSH plasma concentration was observed during the 8-week experiment in both AQ and AC groups. Furthermore, QUR administration did not alter either SOD or MDA serum activity and concentration in any group during the experimental period. Physical examination revealed no differences between the experimental groups. In conclusion, under our experimental conditions, QUR did not modify the general clinical or the antioxidant profile of young and adult reproductive rabbit females., (© 2024 The Author(s). Reproduction in Domestic Animals published by Wiley‐VCH GmbH.)

The basis of most neurological syndromes is the accumulation of free radical molecules. Quercetin is a polyphenolic bioflavonoid molecule and it has a very strong antioxidant effect by maintaining oxidative balance. There are many difficulties in the clinical use of quercetin due to its hydrophobic structure, low solubility, instability, poor oral bioavailability, and limited tissue-barrier penetration. Its synergistic use in complex with gold nanoparticles (AuNPs) could overcome these problems. AuNPs have recently emerged as an attractive candidate for delivery applications of various biomolecules and drugs. The aim of this study was to synthesize two different sized gold nanoparticles (AuNP 20 and AuNP 50 ) modified with polyethyleneimine (PEI) and quercetin, evaluate their potential neuroprotective effects on the in vitro oxidative stress model using DRG primary sensory neurons. It was shown that the antioxidant and anti-apoptotic ability of the bioflavonoid was preserved after exposure to the designed quercetin modified AuNPs. The PEI surface coating increased the stability and biocompatibility of the AuNPs in both sizes. It also potentially enables additional surface functionalization. This study indicates that designed nanoparticles (AuNP-Q-PEI) with different sizes could be a useful potential platform for the treatment of neurodegenerative syndromes or cancer diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Quercetin possesses multiple biological activities. To achieve efficient colon-specific release of quercetin, new composite nanofibers were developed by coating pH-responsive shellac on hydrophilic gelatin through coaxial electrospinning. These composite nanofibers contained bead-like structures. The encapsulation efficiency (87.6-98.5 %) and loading capacity (1.4-4.1 %) varied with increasing the initial quercetin addition amount (2.5-7.5 %). FTIR, XRD, and TGA results showed that the quercetin was successfully encapsulated in composite nanofibers in an amorphous state, with interactions occurring among quercetin, gelatin, and shellac. Composite nanofibers had pH-responsive surface wettability due to the shellac coating. In vitro digestion experiments showed that these composite nanofibers were highly stable in the upper gastrointestinal tract, with quercetin release ranging from 4.75 % to 12.54 %. In vivo organ distribution and pharmacokinetic studies demonstrated that quercetin could be sustainably released in the colon after oral administration of composite nanofibers. Besides, the enhanced anticancer activity of composite nanofibers was confirmed against HCT-116 cells by analyzing their effect on cell viability, cell cycle, and apoptosis. Overall, these novel composite nanofibers could deliver efficiently quercetin to the colon and achieve its sustained release, thus potential to regulate colon health. This system is also helpful in delivering other bioactives to the colon and exerting their functional effects., Competing Interests: Declaration of competing interest There have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Diabetic ulcers present a formidable obstacle in diabetes management, typically leading to high mortality and amputation rates. To overcome traditional monotherapy drawbacks, We developed a novel microneedle strategy for combined antimicrobial action: ingeniously integrating quercetin with Platelet-derived Growth Factor-BB(PDGF-BB) and Sucrose Octasulfate(SOS) into the microneedle system(QPS MN). This method allows to penetrate through biofilms, administering quercetin nanocrystals and PDGF-BB deep into the tissue to combat microbial infection, mitigate inflammation, and promote angiogenesis. The accompanying backing material contains SOS, which absorbs wound exudate and forms a dressing that provides a moist environment for wound healing In an in vitro wound-scratch assay demonstrated that co-cultivating Human Umbilical Vein Endothelial Cells(HUVEC) with QPS MN for 48 h (90.3 ± 2.51 %) significantly enhanced cell migration compared to the control group (20.2 ± 1.41 %). Moreover, treatment of streptozotocin-induced diabetic wounds in rats with QPS MN for 14 days resulted in a wound healing rate of 96.56 ± 3.44 %, far surpassing the healing rate of only 40.34 ± 7.26 % observed in the untreated control group. Furthermore, the QPS MN treated wounds exhibited a notable increase in skin appendages and neovascularisation, indicating promising potential for achieving complete wound healing. These results suggest that QPS MN may offer substantial therapeutic benefits for addressing diabetic wounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A novel multi-functional micelle delivery system was developed for enhancing the oral absorption of paclitaxel (PTX). The delivery carriers were constructed by modifying chitosan-stearic acid (CS-SA) micelles with L-carnitine (LC) and co-encapsulating quercetin (Que), and the PTX-loaded micelles were prepared by film-sonication dispersing technique. The as-prepared micelles showed homogeneous spherical shapes with a small particle size of 148.3 ± 1.7 nm, high drug loading of 7.05% and low critical micelle concentration (CMC) of 16.89 µg/ml. Compared to the in-house PTX formulation similar to the commercial injection Taxol™, the target PTX-loaded micelles had obvious sustained-release effects and exhibited an oral relative bioavailability of 168.08%. The cellular uptake studies of Caco-2 cells confirmed the micellar modification of LC and the co-loading of Que played important roles in promoting the absorption of drug loaded in micelles. The CYP3A4 enzyme test demonstrated the micelles had an inhibitory effect on the metabolic enzyme due to the presence of Que. These findings confirmed the potential of the multi-functional chitosan polymeric micelles based on synergistic effect as an effective oral delivery system., Competing Interests: Declarations. Ethics approval: All institutional and national guidelines for the care and use of laboratory animals were followed. Consent to participate: Written informed consent was obtained from the participants for the publication of this manuscript. Consent for publication: Written informed consent was obtained from the authors for the publication of this manuscript. Competing interests: The authors declare no competing interests., (© 2024. Controlled Release Society.)

Quercetin, a natural compound, shows promising potential in wound healing by reducing fibrosis, limiting scar formation, and boosting fibroblast proliferation. However, its effectiveness is hindered by poor solubility, resulting in low bioavailability and necessitating high doses for therapeutic efficacy. This study presents a novel approach, fabricating quercetin-loaded microarray patches (MAPs) using widely employed solubility enhancement strategies. Fabricated MAPs exhibited favourable mechanical strength and could be inserted into excised porcine skin to a depth of 650 μm. Furthermore, formulations containing Soluplus ® significantly increased the drug loading capacity, achieving up to 2.5 mg per patch and complete dissolution within an hour of application on excised porcine skin. In vitro studies on full-thickness neonatal porcine skin demonstrated that Soluplus ® -enhanced MAPs effectively delivered quercetin across various skin layers, achieving a delivery efficiency exceeding 80% over 24 h. Additionally, these prototype MAPs displayed anti-inflammatory properties and demonstrated biocompatibility with human keratinocyte skin cells. Therefore, quercetin-loaded MAPs employing Soluplus ® as a solubility enhancer present a promising alternative strategy for wound healing and anti-inflammatory therapy applications., Competing Interests: Declarations. Ethical approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interest., (© 2024. The Author(s).)

Background: Oxidative stress has emerged as a key contributor to numerous NCDs (non-communicable diseases), including cardiovascular diseases, cancer, and diabetes. This study aims to explore the potential of targeted interventions to mitigate oxidative stress as part of a primary prevention strategy., Methods: The study included 32 healthy participants (11 men, 21 women) aged 45-65 who completed both the initial and follow-up assessments of the Healthy Days Initiative, a community-based wellness program organized by the non-profit Associazione O.R.A. ETS. Through blood analysis, vital sign assessment, lifestyle questionnaires, and individualized recommendations, participants received guidance on improving their health and reducing disease risk. The initiative also offered the opportunity for participants to consume a flavonoid supplement containing quercitrin, rutin, and hesperidin, with the goal of reducing oxidative stress. Participants who opted for supplementation were instructed to take 1-2 tablets daily for two weeks. Data collected included demographic information, anthropometric measurements, vital signs, dietary and lifestyle habits, medical history, WHO-5 Well-Being Index scores, and blood parameters., Results: Significant reductions were observed in glucose levels (from 82 to 74.5 mg/dL), reactive oxygen metabolites (d-ROMs) (from 394.5 to 365.5 U.CARR), and systolic blood pressure (from 133 to 122 mmHg) after the two-week flavonoid intervention. Most participants (26/31) reported no side effects, and the majority (30/31) expressed a willingness to continue using a product combination of quercitrin, rutin, and hesperidin or a similar product long-term., Conclusions: While limited in scope and duration, the PREVES-FLAVON study contributes valuable insights to the growing body of evidence suggesting that flavonoid supplementation may play a significant role in reducing risk factors associated with NCDs in primary prevention settings. By targeting novel risk factors such as oxidative stress, this intervention holds promise for mitigating the global burden of NCDs and promoting healthy aging.

Introduction: Resistance of intracellular pathogens is a challenge in microbial therapy. Methicillin-resistant Staphylococcus aureus (MRSA), which is able to persist inside the cells of infected tissues, is protected from attack by the immune system and many antimicrobial agents. To overcome these limitations, nano-delivery systems can be used for targeted therapy of intracellular MRSA., Methods: Hyaluronic acid-modified azithromycin/quercetin micelles (HA-AZI/Qe-M) were synthesized by thin film hydration. The micelles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR), and the drug loading (DL) and encapsulation efficiency (EE) were detected by high performance liquid chromatography (HPLC). The uptake ability of RAW264.7 cells was investigated, and its distribution in mice was evaluated by in vivo imaging. The inhibitory effect of the micelles against MRSA in vitro and its ability to eliminate intracellular bacteria were evaluated. Bacterial muscle-infected mice were constructed to evaluate the therapeutic effect of the micelles on bacterial infections in vivo and the biocompatibility of the micelles was investigated., Results: HA-AZI/Qe-M had suitable physical and chemical properties and characterization. In vitro a ntibacterial experiments showed that HA-AZI/Qe-M could effectively inhibit the growth of MRSA, inhibit and eliminate the biofilm formed by MRSA, and have an excellent therapeutic effect on intracellular bacterial infection. The results of RAW264.7 cells uptake and in vivo imaging showed that HA-AZI/Qe-M could increase the cellular uptake, target the infection site, and prolong the treatment time. The results of in vivo antibacterial infection experiments showed that HA-AZI/Qe-M was able to ameliorate the extent of thigh muscle infections in mice and reduce the expression of inflammatory factors., Conclusion: HA-AZI/Qe-M is a novel and effective nano-drug delivery system that can target intracellular bacterial infection, and it is expected to be safely used for the treatment of MRSA infection., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Zhang et al.)

Recent research has emphasized the development of efficient drug delivery systems to facilitate the delivery of biological compounds such as polyphenols via skin absorption. Phytozomes have been employed as carriers of plant compounds in this context Hydrogen bonding between plant polyphenols and the phospholipid phosphate group enables efficient encapsulation of potent compounds for enhanced drug delivery systems. Additionally, the strong affinity of phytosomes for the skin's phospholipids enhances skin absorption. In this study, phytosomes were initially formulated using the thin-layer hydration method After optimizing the synthetic parameters, phytosomes were loaded with Resveratrol and Quercetin for enhanced delivery and skin absorption potential to assess the characteristics of the synthesized phytosomes, tests were conducted to determine particle distribution and size, zeta potential, and examine the microstructure morphology using a scanning electron microscope (SEM). Furthermore, a siloxane gel base was formulated in this study, and the stability of the physicochemical and biological properties of the final prepared nanoformulation was investigated. The results of this study indicated that the formulated phytosomes exhibit optimal characteristics for facilitating high skin penetration of resveratrol and quercetin. A high skin absorption was observed after 60 days of synthesis. Additionally, the base of the siloxane gel can play a significant role in preventing the formation of scars by reducing the passage of water vapor.

A significant impediment persists in developing multicomponent nanomedicines designed to dismantle the heat shock protein (HSP)-based protective mechanism of malignant tumors during photothermal therapy. Herein, well-defined PEGylated phospholipid micelles were utilized to coencapsulate quercetin (QUE, a natural anticancer agent and potent HSP inhibitor) and indocyanine green (ICG, a photothermal agent) with the aim of achieving synchronized and synergistic drug effects. The subsequent investigations validated that the tailored micellar system effectively enhanced QUE's water solubility and augmented its cellular internalization efficiency. Intriguingly, the compositional PEGylated phospholipids induced extraordinary endoplasmic reticulum stress, thereby sensitizing the tumor cells to QUE. Furthermore, QUE played a crucial role in inhibiting the stress-induced overexpression of HSP70, thereby augmenting the photothermal efficacy of ICG. In systemic applications, the proposed nanotherapeutics exhibited preferential accumulation within tumors and exerted notable tumoricidal effects against 4T1 xenograft tumors under 808 nm near-infrared irradiation, facilitated by prominent near-infrared fluorescence imaging-guided chemo-photothermal therapy. Therefore, our strategy for fabricating multicomponent nanomedicines emerges as a coordinated platform for optimizing antitumor therapeutic efficacy and offers valuable insights for diverse therapeutic modalities.

Preclinical evidence demonstrates that senescent cells accumulate with aging and that senolytics delay multiple age-related morbidities, including bone loss. Thus, we conducted a phase 2 randomized controlled trial of intermittent administration of the senolytic combination dasatinib plus quercetin (D + Q) in postmenopausal women (n = 60 participants). The primary endpoint, percentage changes at 20 weeks in the bone resorption marker C-terminal telopeptide of type 1 collagen (CTx), did not differ between groups (median (interquartile range), D + Q -4.1% (-13.2, 2.6), control -7.7% (-20.1, 14.3); P = 0.611). The secondary endpoint, percentage changes in the bone formation marker procollagen type 1 N-terminal propeptide (P1NP), increased significantly (relative to control) in the D + Q group at both 2 weeks (+16%, P = 0.020) and 4 weeks (+16%, P = 0.024), but was not different from control at 20 weeks (-9%, P = 0.149). No serious adverse events were observed. In exploratory analyses, the skeletal response to D + Q was driven principally by women with a high senescent cell burden (highest tertile for T cell p16 (also known as CDKN2A) mRNA levels) in which D + Q concomitantly increased P1NP (+34%, P = 0.035) and reduced CTx (-11%, P = 0.049) at 2 weeks, and increased radius bone mineral density (+2.7%, P = 0.004) at 20 weeks. Thus, intermittent D + Q treatment did not reduce bone resorption in the overall group of postmenopausal women. However, our exploratory analyses indicate that further studies are needed testing the hypothesis that the underlying senescent cell burden may dictate the clinical response to senolytics. ClinicalTrials.gov identifier: NCT04313634 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Chemotherapeutic drug delivery systems are commonly limited by their short half-lives, poor bioavailability, and unsuccessful targetability. Herein, pH-responsive hybrid NPs consist of benzimidazole-coated mesoporous silica nanoparticles (BZ-MSN) loaded with naturally occurring flavonoid quercetin (QUE-BZ-MSN). The NPs were further capped with beta-cyclodextrin (BCD) to obtain our desired BCD-QUE-BZMSN, with a zeta potential around 7.05 ± 2.37 mV and diameter about 115.2 ± 19.02 nm. The abundance of BZ onto the nanoparticles facilitates targeted quercetin chemotherapy against model lung and liver cancer cell lines. FTIR, EDX, and NMR analyses revealed evidence of possible surface functionalizations. Powder XRD analysis showed that our designed BCD-QUE-BZMSN formulation is amorphous in nature. The UV and SEM showed that our designed BCD-QUE-BZMSN has high drug entrapment efficiency and a nearly spherical morphology. In vitro, drug release assessments show controlled pH-dependent release profiles that could enhance the targeted chemotherapeutic response against mildly acidic regions in cancer cell lines. The obtained BCD-QUE-BZMSN nanovalve achieved significantly higher cytotoxic efficacy as compared to QUE alone, which was evaluated by in vitro cellular uptake against liver and lung cancer cell lines, and the cellular morphological ablation was further confirmed via inverted microscopy. The outcomes of the study imply that our designed BCD-QUE-BZMSN nanovalve is a potential carrier for cancer chemotherapeutics.

Background: Nonalcoholic fatty liver disease (NAFLD) has become a growing public health problem worldwide. However, there is still lack of effective treatment strategies except lifestyle intervention., Objectives: To evaluate whether quercetin improves intrahepatic lipid content in patients with NAFLD., Methods: In this randomized, double-blind, placebo-controlled crossover trial, 41 patients with NAFLD were randomly assigned to receive the quercetin (500 mg) or placebo capsules for 12 wk, then switched interventions for another 12 wk after a 4-wk washout period. The primary outcome was intrahepatic lipid content evaluated by magnetic resonance imaging estimated proton density fat fraction. The secondary outcomes were liver function measurements, etc. Safety outcomes included blood routine., Results: A total of 36 patients completed the trial. In intention-to-treat analyses, the quercetin intervention moderately decreased the intrahepatic lipid contents from 11.5% ± 6.4% to 9.6% ± 5.8%, compared with the placebo intervention (decreased by 0.1% ± 2.6%, P = 0.013 and adjusted P value is 0.028). Body weight and body mass index were mildly reduced by 1.5 ± 2.6 kg and 0.5 ± 0.9 kg/m 2 after the quercetin intervention (P < 0.05 and both adjusted P values are 0.038), whereas the reductions were only 0.2 ± 1.8 kg and 0.1 ± 0.7 kg/m 2 after the placebo intervention. The intrahepatic lipid content reductions were noticeably positively associated with the body weight losses after the quercetin and placebo interventions (r = 0.557 and 0.412, P < 0.001 and P = 0.007, respectively). Subgroup analyses found that the reduction of intrahepatic lipid contents in females (3.0% ± 3.7%) was about twice as large as that in males (1.4% ± 2.5%) with a trend of statistical significance (P = 0.113 and adjusted P value is 0.061). There were no significant differences in other secondary and safety outcomes. No adverse events associated with study intervention were found., Conclusions: Twelve weeks treatment of quercetin could reduce intrahepatic lipid contents in patients with NAFLD, possibly explained by a slightly larger body weight loss in the quercetin group., Trial Registration: The trial is registered at www.chictr.org.cn as ChiCTR2100047904., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Advanced targeted nanoparticles (NPs) were designed to enhance the targeted delivery of resveratrol (RES) and quercetin (QUE) by utilizing carboxymethyl chitosan (CTS) and Jiuzao glutelin isolate (JGI) conjugates. Briefly, RES and QUE were encapsuled within CTS-JGI-2 (CTS/JGI, m/m, 2:1). The carrier's targeting properties were further improved through the incorporation of folic acid (FA) and polyethylenimine (PEI). Moreover, the stability against digestion was enhanced by incorporating baker yeast cell walls (BYCWs) to construct RES-QUE/FA-PEI/CTS-JGI-2/MAT/BYCW NPs. The results demonstrated that FA-PEI/CTS-JGI-2/MAT/BYCW NPs could improve cellular uptake and targeting property of RES and QUE through endocytosis of folic acid receptors (FOLRs). Additionally, RES-QUE successfully alleviated LPS- and DSS-induced inflammation by regulating NF-κB/IkBa/AP-1 and AMPK/SIRT1signaling pathways and reducing the secretion of inflammatory mediators and factors. These findings indicate FA-PEI/CTS-JGI-2/MAT/BYCW NPs hold promise as an oral drug delivery system with targeted delivery capacities for functional substances prone to instability in dietary supplements., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives : The aim of the present study was to study the potential therapeutic effects of quercetin in protection against repeated intranasal exposure of an amyloid-beta-induced mouse model. Methods : Mice received intranasal Aβ 1-42 (5 μg/10 μL) exposure once daily for seven consecutive days. Quercetin was orally administered to them at 30 mg kg -1 and 100 mg kg -1 doses for one week starting from day five following Aβ 1-42 peptide administration. Following this, the animals were evaluated for neurobehavioral parameters using a Morris water maze test and a novel object recognition test. Further to this, the biomarkers for neuroinflammation and neurodegeneration were evaluated in the hippocampus and cortex regions of the brain in these animals. Results : Multiple exposures to intranasal Aβ led to a significant decline in the learning and cognitive memory of the animals, whereas oral treatment with quercetin at dosages of 30 and 100 mg kg -1 alleviated Aβ-induced effects. Quercetin treatment significantly reduced Aβ accumulation, oxidative stress and proinflammatory cytokine biomarkers in the brain. In addition, it also alleviated the activation of astrocytic biomarkers, amyloid precursor protein and phosphorylated-tau proteins in the brain. Conclusion : Quercetin was found to be a potent antioxidant, anti-inflammatory compound with protection against neurodegenerative damage and improved learning and cognitive memory in a repeated Aβ-exposure model of AD.

Background: Warfighters, often called tactical athletes, seek dietary supplementation to enhance training and recovery. Roughly 69% of active-duty US military personnel have reported consuming dietary supplements. The objective of this systematic review was to examine the impact of dietary supplements on muscle-related physical performance and recovery in active-duty military personnel., Methods: Randomized controlled trials and quasi-experimental controlled trials of oral dietary supplementation in active-duty military members were examined. A protocol was registered (PROSPERO CRD42023401472), and a systematic search of MEDLINE and CINAHL was undertaken. Inclusion criteria consisted of studies published between 1990-2023 with outcomes of muscle performance and recovery among active-duty military populations. The risk of bias was assessed with the McMaster University Guidelines and Critical Review Form for Quantitative Studies., Results: Sixteen studies were included. Four were conducted on protein or carbohydrate; four on beta-alanine alone, creatine alone, or in combination; two on mixed nutritional supplements; two on probiotics alone or in combination with beta hydroxy-beta methylbutyrate calcium; and four on phytonutrient extracts including oregano, beetroot juice, quercetin, and resveratrol. Ten examined outcomes related to physical performance, and six on outcomes of injury or recovery. Overall, protein, carbohydrate, beta-alanine, creatine, and beetroot juice modestly improved performance, while quercetin did not. Protein, carbohydrates, beta-alanine, probiotics, and oregano reduced markers of inflammation, while resveratrol did not., Conclusions: Nutrition supplementation may have small benefits on muscle performance and recovery in warfighters. However, there are significant limitations in interpretation due to the largely inconsistent evidence of ingredients and comparable outcomes. Thus, there is inadequate practical evidence to suggest how dietary supplementation may affect field performance.

In type 2 diabetes mellitus, hepatic insulin resistance is intricately associated with oxidative stress and inflammation. Nonetheless, the lack of therapeutic interventions directly targeting hepatic dysfunction represents a notable gap in current treatment options. Flavonoids have been explored due to their potential antidiabetic effects. However, these compounds are associated with low bioavailability and high metabolization. In the present study, four flavonoids, kaempferol, quercetin, kaempferol-7-O-glucoside and quercetin-7-O-glucoside, were studied in a cellular model of hepatic insulin resistance using HepG2 cells. Quercetin was selected as the most promising flavonoid and incorporated into liposomes to enhance its therapeutic effect. Quercetin liposomes had a mean size of 0.12 µm, with an incorporation efficiency of 93 %. Quercetin liposomes exhibited increased efficacy in modulating insulin resistance. This was achieved through the modulation of Akt expression and the attenuation of inflammation, particularly via the NF-κB pathway, as well as the regulation of PGE 2 and COX-2 expression. Furthermore, quercetin liposomes displayed a significant advantage over free quercetin in attenuating the production of reactive pro-oxidant species. These findings open new avenues for developing innovative therapeutic strategies to manage diabetes, emphasizing the potential of quercetin liposomes as a promising approach for targeting both hepatic insulin resistance and associated inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Following spinal cord injury, the inflammatory environment at the injury site causes local microglia and astrocytes to activate, which worsens the nerve damage in the affected area. Quercetin, an anti-inflammatory agent, has been limited in spinal cord injury due to its poor water solubility and easy degradation. Stem cell-derived extracellular vesicles can go through the blood-brain barrier and are an ideal drug delivery system. In this study, umbilical cord mesenchymal stem cell-derived extracellular vesicles were used to load quercetin to prevent its degradation and allow it to accumulate at the site of spinal cord injury. Our results showed that quercetin-loaded extracellular vesicles could inhibit the activation of microglia to M1 phenotype through the TLR4/NF-κB pathway, and the activation of astrocytes to A1 phenotype through the JAK2/STAT3 pathway. This reduced the production of inflammatory factors, mitigated neuronal damage, and inhibited the growth of astroglial scar, but promoted the recovery of motor function in rats with spinal cord injury., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)

Inflammatory responses play a crucial role in the pathophysiology of spinal cord injury (SCI) and developing new approaches to establish an anti-inflammatory environment for the promotion of neuroregeneration holds promise as a potential approach. In this study, our aim was to investigate the potential of combining an acellular spinal cord scaffold (ASCS) with quercetin-loaded bovine serum albumin (Qu/BSA) nanoparticles (NPs) for the treatment of SCI. The ASCS was prepared using physical and chemical methods, while the Qu/BSA NPs were prepared through a desolvation technique. The NPs exhibited favorable characteristics, including a mean size of 203 nm, a zeta potential of -38, and an encapsulation efficiency of 96%. Microscopic evaluation confirmed the successful distribution of NPs on the walls of ASCS. Animal studies revealed that Qu/BSA NPs group exhibited a significant decrease in NLRP3, ASC, and Casp1 gene expression compared to the SCI group (p < 0.0001). The findings indicated a significant decrease in the NLRP3, ASC, and Casp1 protein level between the Qu/BSA/ASCS group and the SCI group (p < 0.0001). Moreover, treatment with ASCS containing either blank BSA (B/BSA) NPs or Qu/BSA NPs effectively promoted functional recovery via increasing the amount of nestin- and glial fibrillary acidic protein (GFAP)-positive cells in the site of injury. Notably, Qu/BSA/ASCS exhibited superior outcomes compared to B/BSA/ASCS. Overall, the combination of ASCS with the Qu delivery system presents a promising therapeutic approach for SCI by inhibiting inflammatory responses and promoting neuroregeneration, leading to the restoration of motor function in animals. This study demonstrates the potential of utilizing biomaterials and NPs to enhance the effectiveness of SCI treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

1. The accumulation of excessive fat plays a role in the development of non-alcoholic fatty liver disease (NAFLD) and phytogenic feed additives have the potential to ameliorate this. This study involved the isolation and culture of primary hepatocytes from chicken embryos to establish a model of hepatic steatosis induced by oleic acid/dexamethasone (OA/DEX). Lipid accumulation and cell viability were assessed using Nile Red staining, Oil Red O staining and cell count Kit -8 (CCK8) following treatment with varying concentrations of quercetin (Que). The potential mechanism by which Que exerts its effects was preliminarily investigated.2. The results indicated that OA effectively treated lipid accumulation in hepatocytes. There was no notable variance in cell proliferation between the normal and OA/DEX groups when subjected to Que treatment at concentrations of 1000 ng/ml and 10 000 ng/ml. Triglycerides and cholesterol (low and high density) decreased with Que treatment, with the most substantial reduction observed at 10 000 ng/ml.3. Gene expression levels decreased to levels similar to those in the control groups. Western blot data demonstrated that sterol regulatory element-binding protein 1 (SREBP-1) protein expression correlated with its mRNA expression level. Que mitigated lipid accumulation through the alpha serine/threonine protein kinase (AKT) and extracellular signal-regulated kinase (ERK) pathways. Expression levels of lipid-related genes ( APOB, PPARα, CYP3A5 and SREBP-1 ) decreased to levels similar to the control groups. Western blot data demonstrated that the SREBP-1 protein expression correlated with its mRNA expression level.4. Supplementation with Que ameliorated lipid accumulation through AKT and ERK signalling pathway in OA/DEX-induced high-fat hepatocytes.

The skin's protective functions are compromised over time by both endogenous and exogenous aging. Senescence is well-documented in skin phenotypes, such as wrinkling and sagging, a consequence of the senescence-associated secretory phenotype (SASP) that involves the accumulation of senescent fibroblasts, chronic inflammation, and collagen remodeling. Although therapeutic approaches for eliminating senescent cells from the skin are available, their efficacy remains unclear. Accordingly, we aimed to examine the effects of dasatinib in combination with quercetin (D + Q) on senescent human skin fibroblasts and aging human skin. Senescence was induced in human dermal fibroblasts (HDFs) using approaches such as long-term passaging, ionizing radiation, and doxorubicin treatment. The generated senescent cells were treated with D + Q or vehicle. Additionally, a mouse-human chimera model was generated by subcutaneously transplanting whole-skin grafts of aged individuals onto nude mice. Mouse models were administered D + Q or vehicle by oral gavage for 30 days. Subsequently, skin samples were harvested and stained for senescence-associated beta-galactosidase. Senescence-associated markers were assessed by western blotting, reverse transcription-quantitative PCR and histological analyses. Herein, D + Q selectively eliminated senescent HDFs in all cellular models of induced senescence. Additionally, D + Q-treated aged human skin grafts exhibited increased collagen density and suppression of the SASP compared with control grafts. No adverse events were observed during the study period. Collectively, D + Q could ameliorate skin aging through selective elimination of senescent dermal fibroblasts and suppression of the SASP. Our findings suggest that D + Q could be developed as an effective therapeutic approach for combating skin aging., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Periodontal disease ranks third among noncommunicable illnesses, behind cancer and cardiovascular disease, and is closely related to the occurrence and progression of various systemic diseases. However, elucidating the processes of periodontal disease and promoting periodontal bone regeneration remains a challenge. Here, quercetin is demonstrated to reduce the oxidative stress state of orofacial mesenchymal stem cells (OMSCs) in vitro and to affect the osteogenic growth of OMSCs through molecular mechanisms that mediate the m6A change in Per1. Nevertheless, the limited therapeutic efficacy of systemic medication and the limitations of local medication resulting from the small, moist, and highly dynamic periodontal environment make it challenging to treat periodontal tissues with medication. Herein, a biosafe injectable hydrogel drug-controlled delivery system is constructed as a bone-enhancing factory and loaded with quercetin to treat oxidative stress injury in periodontal tissues. This drug-carrying system made up of nanoscale bioglass microspheres and a light-cured injectable hydrogel, allows effective drug particle loading and cementation in the dynamic and moist periodontal environment. Furthermore, the system demonstrates the ability to stimulate OMSCs osteogenic differentiation in a Per1-dependent manner, which ultimately promotes periodontal bone repair, suggesting that this system has potential for clinical periodontal therapy., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

We investigated the effects of one-week quercetin ingestion on motor unit (MU) behavior and muscle contractile properties before, during, and after a single session of resistance exercise in older adults. Twenty-four older adults were divided into two groups: those receiving quercetin glycosides (QUE) or placebo (PLA), and they performed a single session of resistance exercise. MU behavior before and during resistance exercise and electrically elicited contraction before and after resistance exercise were measured (Day 1), and the same measurements were conducted again after 7 days of placebo or quercetin glycoside ingestion (Day 8). The MU recruitment threshold (RT) was decreased (p < 0.001, 25.6 ± 10.1 to 23.6 ± 9.5 %MVC) and the exerted force normalized by the MU firing rate (FR) was increased (p = 0.003, 1.13 ± 0.24 to 1.18 ± 0.22 %MVC/pps) from Days 1 to 8, respectively, in QUE but not PLA (p = 0.263, 22.6 ± 11.9 to 21.9 ± 11.6 %MVC; p = 0.713, 1.09 ± 0.20 to 1.10 ± 0.19 %MVC/pps, respectively). On Day 1, a significant correlation between MURT and%change in MUFR from the first to last contractions during the resistance exercise was observed in both groups (QUE: p = 0.009, rs = 0.308; PLA: p < 0.001, rs = 0.403). On Day 8 %change in MUFR was negatively correlated with MURT in QUE (p = 0.044, rs = -0.251), but there was no significant correlation in PLA (p = 0.844). There was no difference in electrically elicited contraction before and after the resistance exercise between QUE and PLA (p < 0.05). These results suggest that one-week quercetin ingestion in older adults lowered MURT and led to greater fatigue in MU with higher RT than with lower RT during resistance training., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Context: Spinal cord injury (SCI) is a potentially fatal neurological disease with severe complications and a high disability rate. An increasing number of animal experimental studies support the therapeutic effect of quercetin, which is a natural anti-inflammatory and antioxidant bioflavonoid., Objective: This paper reviewed the therapeutic effect of quercetin on a rat SCI model and summarized the relevant mechanistic research., Data Sources: PubMed, EMBASE, Web of Science, Science Direct, WanFang Data, SinoMed databases, the China National Knowledge Infrastructure, and the Vip Journal Integration Platform were searched from their inception to April 2023 for animal experiments applying quercetin to treat SCI., Study Selection: Based on the PICOS criteria, a total of 18 eligible studies were included, of which 14 were high quality., Results: In this study, there was a gradual increase in effect based on the Basso, Beattie, and Bresnahan (BBB) score after three days ( p  < 0.0001). Furthermore, gender differences also appeared in the efficacy of quercetin; males performed better than females ( p  = 0.008). Quercetin was also associated with improved inclined plane test score ( p  = 0.008). In terms of biochemical indicators, meta-analysis showed that MDA ( p  < 0.0001) and MPO ( p  = 0.0002) were significantly reduced after quercetin administration compared with the control group, and SOD levels were increased ( p  = 0.004). Mechanistically, quercetin facilitates the inhibition of oxidative stress, inflammation, autophagy and apoptosis that occur after SCI., Conclusions: Generally, this systematic review suggests that quercetin has a neuroprotective effect on SCI.

This study aimed to improve the eating quality of yellow-feathered broiler chicks by feeding them corn-soybean meal diets supplemented with 250, 500, and 1,000 mg/kg quercetin. we examined the impact of varying doses of dietary quercetin on the sensory quality of chicken breast meat as well as on the antioxidant enzymes, antioxidant-related signaling molecules, structure and thermal stability of myofibrillar protein (MPs), and microstructure of myogenic fibers in the meat during 24 h of postslaughter aging. Additionally, we investigated the potential correlations among antioxidant capacity, MP structure, and meat quality parameters. The results indicated that dietary supplementations with 500 and 1,000 mg/kg quercetin improved the physicochemical properties and eating quality of yellow-feathered broiler chicken breast meat during 12 to 24 h postslaughter. Additionally, quercetin improved the postslaughter oxidative stress status and reduced protein and lipid oxidation levels. It also increased hydrogen bonding interactions and α-helix content during 6 to 12 h postslaughter and decreased β-sheet content during 12 to 24 h postslaughter in chicken breast MP. This resulted in improved postslaughter MP structure and thermal stability. The correlation results indicated that the enhancement of antioxidant capacity and MP structure enhanced the physicochemical and edible qualities of yellow-feathered broiler chicken breast meat. In conclusion, the current findings suggest that dietary supplementation with quercetin is an ideal approach for improving the eating quality of chicken meat, thereby broadening our understanding of theoretical and technological applications for improving the quality of chicken., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Nanoparticle-mediated thermotherapeutic research strives innovative, multifunctional, efficient, and safe treatments. Our study introduces a novel nanoplatform: the hollow magnetic vortex nanorings within a polydopamine layer (HMVNp), which exhibit dual functionality as magnetic and photothermal agents. Utilizing a "Dual-mode" approach, combining an alternating magnetic field (AMF) with near-infrared (NIR) laser irradiation, HMVNp demonstrated a significant enhancement in heating efficacy (58 ± 8 %, SAR = 1441 vs 1032 W/g) over traditional solid magnetite nanoparticles coated with polydopamine (SMNp). The unique geometry larger surface area to volume ratio facilitates efficient magnetic vortex dynamics and enhanced heat transfer. Addressing the challenge of heat resistant heat shock protein (Hsp) expression, encapsulated quercetin (Q) within HMVNp leverages tumor acidity and dual-mode thermal therapy to enhance release, showing a 28.8 ± 6.81 % increase in Q loading capacity compared to traditional SMNp. Moreover, HMVNp significantly improves contrast for both magnetic resonance imaging (MRI) and photoacoustic imaging (PAI), with an approximately 62 % transverse relaxation (R2 = 81.5 vs 31.6 mM -1 s -1 [Fe]). In vivo studies showed that while single treatments slowed tumor growth, dual-mode therapy with quercetin significantly reduced tumors and effectively prevented metastases. Our study highlights the potential of HMVNp/Q as a versatile agent in thermotherapeutic interventions, offering improved diagnostic imaging capabilities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Liposomes as drug-delivery systems have been researched and applied in multiple scientific reports and introduced as patented products with interesting therapeutic properties. Despite various advantages, this drug carrier faces major difficulties in its innate stability, cancer cell specificity, and control over the release of hydrophobic drugs, particularly quercetin, a naturally derived drug that carries many desirable characteristics for anticancer treatment. To improve the effectiveness of liposomes to deliver quercetin by tackling and mitigating the mentioned hurdles, we developed a strategy to establish the ability to passively target cancerous cells, as well as to increase the bioavailability of loaded drugs by incorporating poly(ethylene glycol), gelatin, and folic acid moieties to modify the liposomal system's surface. This research developed a chemically synthesized gelatin, poly(ethylene glycol), and folic acid as a single polymer to coat drug-loaded liposome systems. Liposomes were coated with gelatin-poly(ethylene glycol)-folic acid by electrostatic interaction, characterized by their size, morphology, ζ potential, drug loading efficiency, infrared structures, differential scanning calorimetry spectra, and drug-releasing profiles, and then evaluated for their cytotoxicity to MCF-7 breast cancer cells, as well as cellular uptake, analyzed by confocal imaging to further elaborate on the in vitro behavior of the coated liposome. The results indicated an unusual change in size with increased coating materials, followed by increased colloidal stability, ζ potential, and improved cytotoxicity to cancer cells, as shown by the cellular viability test with MCF-7. Cellular uptake also confirmed these results, providing data for the effects of biopolymer coating, while confirming that folic acid can increase the uptake of liposome by cancer cells. In consideration of such results, the modified gelatin-poly(ethylene glycol)-folic acid-coated liposome can be a potential system in delivering the assigned anticancer compound. This modified biopolymer showed excellent properties as a coating material and should be considered for further practical applications in the future.

Aim: The study explores the synergistic potential of atorvastatin (ATR) and quercetin (QUER)- loaded solid lipid nanoparticles (SLN) in combating breast cancer. Materials & methods: SLNs were synthesized using a high-shear homogenization method and optimized using Box-Behnken design. The SLNs were characterized and evaluated for their in vitro anticancer activity. Results: The optimized SLN exhibited narrow size distribution (PDI = 0.338 ± 0.034), a particle size of 72.5 ± 6.5 nm, higher entrapment efficiency (<90%), sustained release and spherical surface particles. The in vitro cytotoxicity studies showed a significant reduction in IC 50 values on MDA-MB-231 cell lines. Conclusion: We report a novel strategy of repurposing well-known drugs and encapsulating them into SLNs as a promising drug-delivery system against breast cancer.

We purposed to explore the consequences of the use quercetin and fisetin alone and in combination with pregabalin and gabapentin, which are used in the management of neuropathic pain, and on neuropathic pain in general. The anti-allodynic effect of various doses (5, 10, and 20 mg/kg) of quercetin and fisetin, both singly and in combination with pregabalin and gabapentin, was evaluated by developing a neuropathic pain model induced by chronic constrictive nerve damage in rats. The effectiveness of these flavonoids was investigated by combining them with gabapentin (50 mg/kg) and pregabalin (15 mg/kg), choosing the effectual dose of 10 mg/kg and the dose of 5 mg/kg, which did not show significant antiallodynic effects. In groups combined with gabapentin and pregabalin, it was determined that they showed a significant antiallodynic effect compared with 50 mg/kg gabapentin and 15 mg/kg pregabalin. In conclusion, in our combination studies, it was observed that the effectiveness of gabapentin and pregabalin, was increased and the duration of effect was prolonged when used with lower doses of flavonoids. Based on these findings; it is possible to say that quercetin and fisetin are potential agents that can be used alone or in combination with other effective treatments to alleviate neuropathic pain., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The aim of this study was to investigate the effects of quercetin (QUE) on alleviating the negative effects of high soybean meal diet for spotted sea bass Lateolabrax maculatus. A healthy control group fed a 44% fishmeal diet was used, while the induction control group replaced 50% fishmeal with soybean meal. Subsequently, QUE was added at concentrations of 0.25, 0.50, 0.75, and 1.00 g/kg in the experimental groups. A total of 540 tailed spotted sea bass were randomly divided into 6 groups and fed the corresponding diet for 56 days. The results showed that 40% soybean meal significantly decreased the growth performance and immunity, increased the intestinal mucosal permeability, and caused damage to the intestinal tissue morphology; moreover, there were alterations observed in the composition of the intestinal microbiota, accompanied by detectable levels of saponins in the metabolites. However, the addition of QUE did not yield significant changes in growth performance; instead, it notably reduced the permeability of the intestinal mucosa, improved the body's immunity and the structural integrity of the intestinal tissue, increased the proportion of Proteobacteria, and enhanced the richness and diversity of intestinal microorganisms to a certain extent. In addition, QUE up-regulate the metabolism of amino acids and their derivatives and energy-related metabolites such as uridine and guanosine; furthermore, it appears to regulate transporters through the ABC transporters pathway to promote the absorption and utilization of QUE by enterocytes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD) is a primary cause of dementia that affects millions of people worldwide and its prevalence is likely to increase largely in the coming decades. Multiple complex pathways, such as oxidative stress, tau and amyloid-beta (Aβ) pathology, and cholinergic dysfunction, are involved in the pathogenesis of Alzheimer's disease. The conventional treatments provide only symptomatic relief and not a complete cure for the disease. On the other hand, recent studies have looked into the possibility of flavonoids as an effective therapeutic strategy for treating AD. Quercetin, a well-known flavonol, has been extensively studied for AD treatment. Therefore, this review mainly focuses on the pharmacokinetics properties of quercetin and its modes of action, such as antioxidant, anti-inflammatory, anti-amyloidogenic, and neuroprotective properties, which are beneficial in treating AD. It also highlights the nano delivery systems of quercetin, including liposomes, nanostructures lipid carriers, solid lipid nanoparticles, nanoemulsions, microemulsions, self-emulsifying drug delivery systems, and nanoparticles reported for AD treatment. The remarkable potential of quercetin nanocarriers has been reflected in enhancing its bioavailability and therapeutic efficacy. Therefore, clinical studies must be conducted to explore it as a therapeutic strategy for Alzheimer's disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The purpose of this study was to investigate the impact of different functional stabilizers on in vitro/in vivo drug performances after oral administration of drug nanocrystals. Quercetin nanocrystals (QT-NCs) respectively stabilized by five types of functional stabilizers, including hydroxypropyl methyl cellulose E15 (HPMC E15), poloxamer 407 (P407), poloxamer 188 (P188), D-α-tocopherol polyethylene glycol succinate (TPGS), and glycyrrhizin acid (GL), were fabricated by wet media milling technique. The particle size, morphology, physical state, drug solubility, drug dissolution in vitro , and orally pharmacokinetic behaviors of all QT-NCs were investigated. All QT-NCs with similar particle size about 200 nm were obtained by controlling milling speed and milling time. No significant differences in particles shape and crystalline nature were found for QT-NCs stabilized by different functional stabilizers. But the solubility and dissolution of QT-NCs were significantly influenced by the different functional stabilizers. The AUC 0∼ t of all QT-NCs after oral administration was in the following order: QT-NCs/P188 ≈ QT-NCs/HPMC E15 > QT-NCs/GL > QT-NCs/P407 ≈ QT-NCs/TPGS, and the C max showed an order of QT-NCs/P407 > QT-NCs/P188 ≈ QT-NCs/GL > QT-NCs/HPMC E15 > QT-NCs/TPGS. Both of QT-NCs/P407 and QT-NCs/TPGS exhibited faster oral absorption with T max at 0.5 h and 0.83 h, respectively, while the other three QT-NCs (QT-NCs/P188, QT-NCs/GL and QT-NCs/HPMC E15) showed a relatively slow absorption with same T max at 5.33 h. The longest MRT 0∼ t (11.72 h) and t 1/2z (32.22 h) were observed for QT-NCs/HPMC E15. These results suggested that the different functional stabilizers could significantly influence on drug solubility, drug dissolution in vitro and orally pharmacokinetic behavior of QT-NCs, and it is possible to alter the drug dissolution in vitro , oral absorption and drug retention in vivo by changing the type of functional stabilizers in NCs preparation.

Regulating the process of epithelial-mesenchymal transition(EMT) is an essential strategy to inhibit tumor growth and metastasis. This study is based on the EMT process of retinoblastoma and constructs quercetin(QUE) and doxorubicin(DOX) co-loaded liposome(QD Lipo) to investigate the therapeutic effect and mechanisms of combined QUE and DOX treatment on retinoblastoma. Single-factor experiments were conducted to optimize the prescription process of QD Lipo. Eventually, spherical particles with a diameter of(108.87±1.93) nm, a PDI of 0.13±0.02, and a Zeta potential of(-34.83±1.92) mV were obtained. The encapsulation rates of QUE and DOX were 96.20%±4.40% and 91.17%±4.41%, respectively. Y79 human retinoblastoma cells were used as an in vitro cellular model, and confocal microscopy demonstrated that QD Lipo could enhance Y79 uptake efficiency. The CCK-8 assay confirmed that the optimal combination therapy effect of QUE and DOX occurred at a mass ratio of 1∶1 to 1∶2. Flow cytometry showed that QD Lipo enhanced the induction of apoptosis in Y79 cells. Western blot analysis revealed that QD Lipo significantly reduced the expression of EMT pathway-related proteins vimentin and α-SMA. Fluorescence assays detected a significant decrease in ROS levels in Y79 cells after treatment with QD. These results indicated that liposomal co-delivery of QUE and DOX can enhance drug delivery efficiency to retinoblastoma cells, inhibit the EMT process in retinoblastoma by downregulating ROS levels, and enhance the cytotoxicity of DOX against retinoblastoma.