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A novel core-shell structured alginate-based hydrogel bead modified by co-gelatinizing with starch and protocatechuic acid (PA), was designed to modulate physical properties of beads, release behavior and antioxidant stability of encapsulated bioactives. Core was fabricated by ionotropic gelation, and its formulation (ratio of sodium alginate/starch) was determined by particle size/starch distribution, texture and bioactive encapsulation capacity of core. Then, coating core with shell-forming solution co-gelatinized with different doses of PA, and subsequently cross-linked with Ca 2+ to obtain core-shell structured beads. Surface microstructure, mechanical characteristics, and swelling ratio of beads were affected by concentrations of PA. Besides, core-shell structure containing PA could enhance delivery and sustained release of encapsulated phenolic bioactives during in vitro digestion, and improve their antioxidant potential stability. Furthermore, interaction between PA and polysaccharide components was elucidated by FTIR and TGA. The present information was beneficial for the advancement of functional food materials and bioactive delivery 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 © 2023. Published by Elsevier Ltd.)

Rare earth elements (REEs), vital and limited resources, also play a significant role in agriculture. Previous findings indicated that the proper concentration of REEs could enhance the germination process, seed germination rate, and seedling growth and development. This paper introduces designing, synthesizing, and assembling a new type of tapered nanogates for separating and detecting lanthanide ions (La 3+ ). A phosphoric acid pillar[5]arene (PP5) was synthesized and incorporated as a receptor molecule for La 3+ in aqueous media. Incorporating these receptor molecules into the nanogates enhances the identification and controlled release of the lanthanide ions in water. The UV titration and COMSOL simulation results demonstrated an interaction between PP5 and La 3+ to strengthen the understanding of the release mechanism. Finally, the effect of released La 3+ on the germination of wheat seeds is discussed, demonstrating the ability to improve its application in the agricultural industry.

Intravaginal rings (IVRs) are long-acting drug device systems designed for controlled drug release in the vagina. Commercially available IVRs employ a one-size-fits-all development approach, where all patients receive the same drug in similar doses and frequencies, allowing no space for dosage individualization for specific patients' needs. To allow flexibility for dosage individualization, this study explores the impact of infill-density on critical characteristics of personalized IVRs, manufactured using droplet deposition modeling three-dimensional (3D) printing technology. The model drug was dispersed on the surface of thermoplastic polyurethane pellets using an oil coating method. IVR infill-density ranged from 60 to 100 %. The compatibility of the drug and matrix was assessed using thermal and spectroscopic analyses. The IVRs were evaluated for weight, porosity, surface morphology, mechanical properties, and in vitro drug release. The results demonstrated high dimensional accuracy and uniformity of 3D-printed IVRs, indicating the robustness of the printing process. Increasing infill-density resulted in greater weight, storage modulus, Young's modulus, Shore hardness, and compression strength, while reducing the porosity of IVRs. All IVRs showed a controlled drug release pattern when tested under accelerated conditions of temperature for 25 days. Notably, greater infill-densities were associated with a decrease in the percentage of drug released. Overall, the study demonstrated that infill-density was an important parameter for personalizing the critical characteristics of the 3D-printed IVRs to fit individual patient needs., 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., (Published by Elsevier B.V.)

Rifampicin (RIF) is commonly used in the treatment of tuberculosis (TB), a bacterium that currently infects one fourth of the world's population. Despite the effectiveness of RIF in treating TB, current RIF treatment regimens require frequent and prolonged dosing, leading to decreased patient compliance and, ultimately, increased mortality rates. This project aims to provide an alternative to oral RIF by means of an inhalable spray-dried formulation. TB uses alveolar macrophages to hide and replicate until the cells rupture, further spreading the bacteria. Therefore, delivering RIF directly to the lungs can increase the drug concentration at the site of infection while reducing off-site side effects. Cyclodextrin (CD) was used to create a RIF-CD inclusion complex to increase RIF solubility and biodegradable RIF-loaded NP (RIF NP) were developed to provide sustained release of RIF. RIF NP and RIF-CD inclusion complex were spray dried to form a dry powder nanocomposite microparticles (nCmP) formulation (RIF-CD nCmP). RIF-CD nCmP displayed appropriate aerosol dispersion characteristics for effective deposition in the alveolar region of the lungs (4.0 µm) with a fine particle fraction of 89 %. The nCmP provided both a burst release of RIF due to the RIF-CD complex and pH-sensitive release of RIF due to the RIF NP incorporated into the formulation. RIF-CD nCmP did not adversely affect lung epithelial cell viability and RIF NP were able to effectively redisperse from the nCmP after spray drying. These results suggest that RIF-CD nCmP can successfully deliver RIF to the site of TB infection while providing both immediate and sustained release of RIF. Overall, the RIF-CD nCmP formulation has the potential to improve the efficacy for the treatment of TB., 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 utilization of three-dimensional (3D) printing technology is prevalent in the fabrication of oral sustained release preparations; however, there is a lack of research on 3D-printed osmotic pump tablets. A 3D-printed core-shell structure bezafibrate osmotic pump tablet was developed based on the characteristics of rapid absorption and short half-life of bezafibrate, utilizing semisolid extrusion (SSE) 3D printing technology. First, the properties of different shell materials were investigated to define the composition of the shell, and ultimately, the optimal formulation was found to be ethyl cellulose:cellulose acetate:polyethylene glycol = 2:1:2. The formulation of the tablet core was defined based on the printing performance and release behavior. The formulation consisted of bezafibrate, lactis anhydrous, sodium bicarbonate, sodium alginate, polyethylene oxide and sodium dodecyl sulfate at a ratio of 400:400:300:80:50:50. The tablet was capable of achieving zero-order release. The physicochemical properties were also characterized. The pharmacokinetic data analysis indicated that there were no statistically significant differences in the pharmacokinetic parameters between the 3D-printed tablets and the reference listed drugs. There was a strong correlation between the in vitro and in vivo results for the 3D-printed tablets. The results showed that SSE printing is a practical approach for manufacturing osmotic pump tablets., 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.)

Reconstruction of bone defects has long been a major clinical challenge. Limited by the various shortcomings of conventional treatment like autologous bone grafting and inorganic substitutes, the development of novel bone repairing strategies is on top priority. Injectable biomimetic hydrogels that deliver stem cells and growth factors in a minimally invasive manner can effectively promote bone regeneration and thus represent a promising alternative. Therefore, in this study, we designed and constructed an injectable nanocomposite hydrogel co-loaded with Laponite (Lap) and vascular endothelial growth factor (VEGF) through a simplified and convenient scheme of physical co-mixing (G@Lap/VEGF). The introduced Lap not only optimized the injectability of GelMA by the electrostatic force between the nanoparticles, but also significantly delayed the release of VEGF-A. In addition, Lap promoted high expression of osteogenic biomarkers in mesenchymal stem cells (MSCs) and enhanced the matrix mineralization. Besides, VEGF-A exerted chemotactic effects recruiting endothelial progenitor cells (EPCs) and inducing neovascularization. Histological and micro-CT results demonstrated that the critical-sized calvarial bone defect lesions in the SD rats after treated with G@Lap/VEGF exhibited significant in vivo bone repairing. In conclusion, the injectable G@Lap/VEGF nanocomposite hydrogel constructed in our study is highly promising for clinical transformation and applications, providing a convenient and simplified scheme for clinical bone repairing, and contributing to the further development of the injectable biomimetic hydrogels., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Lequn Shan reports financial support was provided by Key Research and Development Program of Shaanxi Province. If there are other authors, they 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 Inc. All rights reserved.)

Introduction: Deep, second- and third-degree burn injuries may lead to irreversible damage to the traumatized tissue and to coagulation or thrombosis of the microvessels, further compromising wound healing. Engineered, morphologically gradient drug-eluting nanofiber dressings promote wound healing by mimicking tissue structure and providing sustained drug delivery, which is particularly beneficial for wound management., Methods: This study exploited a resorbable, radially aligned nanofiber dressing that provides the sustained gradient release of metformin at the wound site using a pin-ring electrospinning technique and a differential membrane-thickness approach., Results: The experimental results suggested that the electrospun nanofibrous dressings exhibited uniform and radially oriented fiber distributions. In vitro, these dressings offered an extended release of metformin for 30 d. The incorporation of water-soluble metformin significantly enhanced the hydrophilicity of the nanofiber membranes. Moreover, the in vivo burn-wound-healing model of rats showed that the radially aligned gradient metformin-eluting poly(lactic-co-glycolic acid) (PLGA) nanofibers exhibited significantly superior healing capability compared to the pristine PLGA, metformin-eluting, and control dressings. Histological images showed that the mesh/nanofibers produced no adverse effects., Conclusion: The findings in this study emphasize the potential of resorbable, radially aligned nanofiber dressings as advanced wound care solutions, offering broad applicability and meaningful clinical impact., Competing Interests: The authors declare no conflict of interest regarding the publication of this paper., (© 2024 Chen et al.)

In this work, 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (AHMT) was pre-doped into agarose hydrogels; consequently, sustained hydrogel systems with modulated release performance were constructed for simple operation and recyclability in point-of-care detection of formaldehyde (FA). With the increase in FA concentrations, the absorbance response of the supernatant solutions showed linear relationships and the color of the reaction mixtures gradually increased. The detection limit was calculated to be 0.013 μg mL -1 . To verify its practical application, a simple, rapid and low-cost FA detection platform was built on the basis of the optimized conditions, and the method shows the merits of simplicity, high sensitivity and selectivity. More importantly, the developed hydrogels are recyclable and can be used at least five times without any loss in sensing performance. Significantly, the sensory hydrogels can be employed by non-skilled people for monitoring food safety and applied for the practical detection of FA in foods.

To develop an optimized controlled-release system based on temperature-sensitive poly(N-isopropylacrylamide) (PNIPAAm) nanofibers, we prepared three types of temperature-controlled preservative films. These films were composed of PNIPAAm, polyvinyl alcohol (PVA), polylactic acid (PLA), and lemon essential oil (LEO), and were fabricated using uniaxial, coaxial, and layered spinning techniques. The nanofiber films obtained by layered spinning exhibited a sandwich structure, demonstrating superior physical barrier properties, mechanical strength, and thermal resistance. Fourier-transform infrared spectroscopy confirmed the hydrogen bonding interaction between the polylactic acid/lemon essential oil and PNIPAAm layers. LEO release tests showed that PNIPAAm functions as a temperature-responsive switch, suppressing LEO release below and promoting it above the critical solution temperature. After a sustained release at 40 °C for 5 days, the layered film maintained significant antibacterial activity, effectively extending the shelf life of blackberries to 4 days. Considering its physical barrier, mechanical, and sustained-release properties, the layered film derived from PNIPAAm shows great potential as an intelligent temperature-controlled cling film to effectively extend the freshness of perishable 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.)

In situ forming implants (ISFIs) composed of biodegradable polymers and biocompatible solvents are generally designed for sustained drug release. In this study, a non-invasive computed tomography (CT) imaging approach is used to achieve real time imaging of ISFIs in vivo and in vitro using leuprolide acetate in situ forming implant as a model drug product. The process of implant formation, inner structure change and their impact on drug release were elucidated. Real-time drug distribution was unveiled by the CT contrast agent, iohexol, where it shows a core-shell structure of the deposition. The incorporation of leuprolide acetate (LA) led to a reduced extent of burst release, prolongated release profile, and extended implant size expansion. LA was found to interact with the solvent and slowed down the polymer phase inversion, thus significantly changed the drug distribution in the implant and reduced the drug release. The implant inner structure identified through SEM, implant size change, and polymer degradation along with the CT real time imaging all consistently support the implant formation differences and their implant on the drug release. Similar patterns of implant size expansion and iohexol distribution in the implants were observed both in vitro and in vivo for the implants with and without LA. The comprehensive understanding of the impact of implant formation on drug release through real time CT imaging facilitates the ISFI product development and evaluation., 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 B.V.)

Sustained release microspheres loaded with goserelin are regarded as a promising candidate for treating prostate cancer and other sex hormone diseases. However, their widespread adoption has been hindered by issues such as wide particle size distribution and unstable release characteristics. To address these challenges, we employed a combination of the solid-in-oil-in-water microspheres preparation approach (S/O/W) and innovative premix membrane emulsification technology and deeply investigated the effects of four key parameters on the loaded performance of microspheres and the microscopic mechanisms behind them. With this approach, we successfully produced goserelin-loaded sustained release microspheres of narrow particle size distribution (Span 0.642), remarkable encapsulation efficiency (DL = 4.23 %, EE = 93.98 %), low initial burst release (about 0.50 % within 2 h), and compatibility with small injection needles (23-G, inner diameter 0.33 mm, outer diameter 0.64 mm, maximal force 59 N). In the animal model(administered dose, 2.4 mg·Kg -1 ), goserelin long-acting sustained release microspheres sustained release for over 32 days, maintaining effective concentrations above 2 ng·mL -1 , and effectively reduced serum testosterone concentrations to castration levels (<1.0 ng·mL -1 ) by day 4, maintaining this inhibition for up to 21 days, exhibiting comparable efficacy to the positive control group. In vivo release kinetics analysis revealed that goserelin-loaded sustained release microspheres exhibited a release pattern dominated by diffusion with corrosion assistance in vivo. In summary, the systematic and comprehensive evaluation of uniform-sized goserelin-loaded sustained release microspheres has highlighted their excellent translational potential, and the study herein may provide new strategies and ideas for the development of microsphere dosage forms., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study., (Copyright © 2024. Published by Elsevier B.V.)

Implant-associated bacterial infections are a primary cause of complications in orthopedic implants, and localized drug delivery represents an effective mitigation strategy. Drawing inspiration from the morphology of desiccated soil, our group has developed an advanced drug-delivery system augmented onto titanium (Ti) plates. This system integrates zinc oxide (ZnO) nanorod arrays with a vancomycin drug layer along with a protective Poly(lactic-co-glycolic acid) (PLGA) coating. The binding between the ZnO nanorods and the drug results in attached drug blocks, isolated by desiccation-like cracks, which are then encapsulated by PLGA to enable sustained drug release. Additionally, the release of zinc ions and the generation of reactive oxygen species (ROS) from the ZnO nanorods enhance the antibacterial efficacy. The antibacterial properties of ZnO nanorod-drug-PLGA system have been validated through both in vitro and in vivo studies. Comprehensive investigations were conducted on the impact of bacterial infections on bone defect regeneration and the role of this drug-delivery system in the healing process. Furthermore, the local immune response was analyzed and the immunomodulatory function of the system was demonstrated. Overall, the findings underscore the superior performance of the ZnO nanorod-drug-PLGA system as an efficient and safe approach to combat implant-associated bacterial infections. STATEMENT OF SIGNIFICANCE: Implant-associated bacterial infections pose a significant clinical challenge, particularly in orthopedic procedures. To address this, we developed an innovative ZnO nanorod-drug-PLGA system for local antibiotic delivery on conventional titanium implants. This system is biodegradable and features a unique desiccation-like structure that enables sustained drug release, along with the active substances released from the ZnO nanorods. In a rat calvarial defect model challenged with S. aureus, our system demonstrated remarkable antibacterial efficacy, significantly enhanced bone defect regeneration, and exhibited local immunomodulatory effects that support both infection control and osteogenesis. These breakthrough findings highlight the substantial clinical potential of this novel drug delivery system and introduce a transformative coating strategy to enhance the functionality of traditional metallic biomaterials., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: D. Zhu is a scientific advisor of Summit Life Science Research Institute., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

This study presents an innovative approach to develop and characterize an alginate sponge containing κ-carrageenan (κ-CRG) beads loaded with curcumin. The beads were fabricated using varying concentrations of κ-CRG, and their properties were extensively evaluated using inverted phase-contrast microscopy, Scanning Electron Microscopy (SEM), FTIR, swelling behavior, mass distribution, encapsulation efficiency, in vitro drug release and kinetics of drug release. Beads formulated with specific concentrations of κ-CRG that exhibited optimal performance were then integrated into an alginate sponge matrix, which underwent similar comprehensive testing procedures as the individual beads. The characterized beads displayed a spherical morphology, a notable swelling degree of approximately 146 %, excellent mass uniformity, encapsulation efficiencies higher than 90 % and drug release rate exceeding 70 %. Moreover, the alginate sponge formulation demonstrated a satisfactory drug release profile of 67.9 ± 0.6 %. In terms of drug release kinetics, the Higuchi model was the most effective in explaining the release of curcumin from beads and sponge. These findings underscore the potential of both the beads and the sponge as effective vehicles for the controlled delivery of curcumin, positioning them as promising candidates for pharmaceutical applications across various fields., 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.)

Reducing pesticide residues while extending their efficacy period is a critical challenge in the development of controlled-release pesticides. This study focuses on loading avermectin onto lignin-modified epoxy resin nanocarriers via the creation of photostable nanocapsules (NCs) for evaluating their efficacy against Plutella xylostella. This study also assesses the NCs' resistance to water scour on plant leaves by comparing them with traditional preparations. These NCs feature a stable core-shell structure, an encapsulation efficiency of 92.90 % and slow-release properties. Compared to emulsifiable concentrate (EC) and microemulsion (ME) under UV irradiation, the loading of nanocarriers significantly prolonged the degradation time of avermectin by fivefold. The Nano-formula demonstrated enhanced insecticidal activity in comparison to traditional preparations. Field tests revealed that the efficacy of the NCs on Day 7 (92.55 %) and Day 14 (78.54 %) significantly surpassed that of traditional preparations. Additionally, NCs are more readily washed off cabbage leaves by water than EC and ME, aiding in the reduction of pesticide residues. This technology is particularly suitable for leafy vegetable crops in arid regions or greenhouses, enhancing effectiveness period while minimizing pesticide residues. This research offers novel insights and directions for the development of controlled-release pesticides., 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 B.V.)

In recent years nanotechnologies have been applied to human health with promising results, especially in the field of drug delivery. Polymeric nanoparticles (NPs) have garnered much importance in controlled drug delivery owing to their size. Chitosan (Cs) is a well-recognized biopolymer and Cs NPs have been widely explored in drug delivery. Nonetheless, reports pertaining to green synthesis of Cs NPs are scarce. Thus, in this study, green synthesis of Cs NPs was accomplished from raw mango peel extract. Spherical Cs NPs with positively charged surface of 33.4 mV was accomplished by this process. Cs NPs, in varied content, were integrated in a guar gum network matrix resulting in a nanocomposite hydrogel. The mechanical and thermal stability of the hydrogel improved upon addition of Cs NPs. The hydrogel exhibited smart swelling, good antioxidant and anti-inflammatory propensities. Cs NPs encapsulating 5-Fluorouracil demonstrated a controlled release drug profile in the colorectum and the kinetics implied the anomalous nature of drug release mechanism. The exposure of the drug-loaded nanocomposite hydrogel displayed improved anticancer effects in HT-29 colon cancer cells. Taken altogether, this study puts forth the greater efficacy of Cs NPs in controlled drug delivery for anticancer therapy., 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.)

Oxidative stress has long been known as a pathogenic factor of ulcerative colitis. Superoxide dismutase (SOD) has been demonstrated to mitigate gut mucosal injury via combating oxidative stress. Herein, we developed SOD-loaded multivesicular liposomes (S-MVLs) as sustained-release depot for ulcerative colitis treatment. S-MVLs were spherical honeycomb-like particles with average particle size of 27.3 ± 5.4 μm and encapsulating efficiency of 78.7 ± 2.6 %. Moreover, the two-phase release profiles of SOD from S-MVLs were exhibited, that was, the burst release phase within 4 h and the sustained-release phase within 96 h. After intraperitoneally injecting S-MVLs, in situ retention time of SOD at bowel cavity extended by 4-fold in comparison with SOD solution. In vitro cells experiment showed that S-MVLs had the protective effect on LPS-treated RAW 264.7 cells via scavenging ROS and inhibiting pro-inflammatory cytokines production. S-MVLs ameliorated the body weight loss, DAI score and the colon shortening of colitis mice. Meanwhile, the colonic morphology and the epithelial barrier of colitis mice were effectively recovered after S-MVLs treatment. The therapeutic mechanism might be associated with polymerizing M1 macrophages to M2 phenotypes and alleviating oxidative stress. Collectively, multivesicular liposomes might be a promising sustained-release depot of SOD for ulcerative colitis treatments., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Helin Xu reports financial support was provided by Wenzhou Medical University. If there are other authors, they 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.)

Advanced-stage liver cancers are associated with poor prognosis and have limited treatment options, often leading the patient to hospice care. Percutaneous intratumoral injection of anticancer agents has emerged as a potential alternative to systemic therapy to overcome tumor barriers, increase bioavailability, potentiate immunotherapy, and avoid systemic toxicity, which advanced-stage cancer patients cannot tolerate. Here, an injectable OncoGel (OG) comprising of a nanocomposite hydrogel loaded with an ionic liquid (IL) is developed for achieving a predictable and uniform tumor ablation and long-term slow release of anticancer agents into the ablation zone. Rigorous mechanical, physiochemical, drug release, cytotoxicity experiments, and ex vivo human tissue testing identify an injectable version of the OG with bactericidal properties against highly resistant bacteria. Intratumoral injection of OG loaded with Nivolumab (Nivo) and doxorubicin (Dox) into highly malignant tumor models in mice, rats, and rabbits demonstrates enhanced survival and tumor regression associated with robust tissue ablation and drug distribution throughout the tumor. Mass cytometry and proteomic studies in a mouse model of colorectal cancer that often metastasizes to the liver indicate an enhanced anticancer immune response following the intratumoral injection of OG. OG may augment immunotherapy and potentially improve outcomes in liver cancer patients., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Polyurethane (PU) has a diverse array of customized physical, chemical, mechanical, and structural characteristics, rendering it a superb option for biomedical applications. The current study involves modifying the polyurethane surface by the process of aminolysis (aminolyzed polyurethane; PU-A), followed by covalently immobilizing Carboxymethyl cellulose (CMC) polymer utilizing Schiff base chemistry. Oxidation of CMC periodically leads to the creation of dialdehyde groups along the CMC chain. When the aldehyde groups on the OCMC contact the amine group on a modified PU surface, they form an imine bond. Scanning electron microscopy (SEM), contact angle, and X-ray photoelectron spectroscopy (XPS) techniques are employed to analyze and confirm the immobilization of OCMC on aminolyzed PU film (PU-O). The OCMC gel incorporates Nitrofurantoin (NF) and immobilizes it on the PU surface (PU-ON), creating an antibacterial PU surface. The confirmation of medication incorporation is achieved using EDX analysis. The varying doses of NF have demonstrated concentration-dependent bacteriostatic and bactericidal effects on both Gram-positive and Gram-negative bacteria, in addition to sustained release. The proposed polyurethane (PU-ON) surface exhibited excellent infection resistance in in vivo testing. The material exhibited biocompatibility and is well-suited for biomedical applications., (© 2024 Wiley‐VCH GmbH.)

Deep infection is the second most common complication of arthroplasty following loosening of the implant. Antibiotic-loaded bone cements (ALBCs) and high concentrations of systemic broad-spectrum antibiotics are commonly used to prevent infections following injury and surgery. However, clinical data fails to show that ALBCs are effective against deep infection, and negative side effects can result following prolonged administration of antibiotics. Additionally, the rise of multidrug resistant (MDR) bacteria provides an urgent need for alternatives to broad-spectrum antibiotics. Phage therapy, or the use of bacteriophages (viruses that infect bacteria) to target pathogenic bacteria, might offer a safe alternative to combat MDR bacteria. Application of phage therapy in the setting of deep infections requires formulation strategies that would stabilize bacteriophage against chemical and thermal stress during bone-cement polymerization, that maintain bacteriophage activity for weeks or months at physiological temperatures, and that allow for sustained release of phage to combat slow-growing, persistent bacteria. Here, we demonstrate the formulation of three phages that target diverse bacterial pathogens, which includes spray-drying of the particles for enhanced thermal stability at 37 °C and above. Additionally, we use atomic layer deposition (ALD) to coat spray-dried powders with alumina to allow for delayed release of phage from the dry formulations, and potentially protect phage against chemical damage during bone cement polymerization. Together, these findings present a strategy to formulate phages that possess thermal stability and sustained release properties for use in deep infections., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The University of Colorado has licensed intellectual property related to thermal stabilization and ALD coatings of vaccines to VitriVax, Inc., a company in which the Regents of the University of Colorado and TWR hold equity., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

To improve drug bioavailability, eye drops can be replaced by drug-eluting contact lenses. However, issues of drug leaching from lenses during manufacture and storage, and sterilization, currently limit their commercial application. To address the issues, stimuli-(lysozyme)-sensitive chitosan nanoparticles were developed to provide controlled ocular drug delivery. Nanoparticles were prepared by ionic gelation and characterized by TEM, X-ray diffraction, DSC, and FTIR. In the flux study, conventional-soaked contact lenses (SM-TM-CL) showed high-burst release, while with direct drug-only laden contact lenses (DL-TM-CL) the drug was lost during extraction and sterilization, as well as having poor swelling and optical properties. The nanoparticle-laden contact lenses (TM-Cht-NPs) showed controlled release of timolol for 120 h in the presence of lysozyme, with acceptable opto-physical properties. In the shelf-life study, the TM-Cht-NPs contact lenses showed no leaching or alteration in the drug release pattern. In animal studies, the TM-NPs-CL lenses gave a high drug concentration in rabbit tear fluid (mean = 11.01 µg/mL for 56 h) and helped maintain a low intraocular pressure for 120 h. In conclusion, the chitosan nanoparticle-laden contact lenses demonstrated the potential application to treat glaucoma with acceptable opto-physical properties and addressed the issues of drug-leaching during sterilization and storage., (© 2024. Controlled Release Society.)

Nucleoside antivirals are a leading class of compounds prescribed as a first-line treatment for viral infections. However, inherent limitations such as low solubility and circulation lifetime can necessitate multi-intraday dosing. Here, we deploy the 1,2-dialdehyde glyoxal to generate antiviral nucleoside prodrugs with enhanced pharmacokinetic properties and extended-release activity to combat poor patient adherence. The near-quantitative reaction of glyoxal with acyclovir (ACV) drastically improves ACV solubility and enables subsequent drug release with a half-life of 1.9 h under physiological conditions. Further, glyoxal caging thermoreversibly disrupts ACV activity against HIV-1 reverse transcription in vitro and HSV-1 pathology in cellulo . Finally, the amenability of a panel of nucleoside reverse transcriptase inhibitors to glyoxal caging showcases the potential of this highly versatile method for achieving timed-release activation of a clinically important class of antiviral therapeutics.

Mycotoxins are representative contaminants causing food losses and food safety problems worldwide. Thymol can effectively inhibit pathogen infestation and aflatoxin accumulation during grain storage, but high volatility limits its application. Here, a thymol-betaine co-crystal system was synthesized through grinding-induced self-assembly. The THY-TMG co-crystal exhibited excellent thermal stability with melting point of 91.2 °C owing to abundant intermolecular interactions. Remarkably, after 15 days at 30 °C, the release rate of thymol from co-crystal was only 55%, far surpassing that of pure thymol. Notably, the co-crystal demonstrated the ability to bind H 2 O in the environment while controlling the release of thymol, essentially acting as a desiccant. Moreover, the co-crystals effectively inhibited the growth of Aspergillus flavus and the biosynthesis of aflatoxin B 1 . In practical terms, the THY-TMG co-crystal was successful in preventing AFB 1 contamination and nutrients loss in peanuts, thereby prolonging their shelf-life under conditions of 28 °C and 70% RH., 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.)

Gelatin (GEL), pectin (PEC), carboxymethyl cellulose (CMC), and whey protein isolate (WPI) were employed to formulate hydrogels for stabilizing N-Acetylneuraminic Acid (NeuAc). GEL/WPI-NeuAc hydrogels, irrespective of the ratio, exhibited a flexible and smooth surface with a continuous three-dimensional network structure internally. Porosity of the three types of hydrogels increased from 3.69% to 86.92% (GEL/WPI), 41.67% (PEC/WPI), and 87.62% (CMC/WPI), rendering them suitable as carriers for NeuAc encapsulation. The dynamic swelling behavior of all hydrogels followed Schott's second-order kinetics model. The degradation performance of GEL, PEC, and CMC/WPI-NeuAc hydrogels was optimal at a 5: 5 ratio, with degradation rates of 80.39 ± 1.26%, 82.38 ± 1.96%, and 81.39 ± 1.57%, respectively. GEL, PEC, CMC/WPI-NeuAc hydrogels demonstrated decreased release rates of 44.56%, 31.04%, and 41.26%, respectively, compared to free NeuAc, post gastric digestion. The present investigation suggests the potential of GEL/WPI hydrogels as effective carriers for delivering NeuAc encapsulation., 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.)

Hollow hydrogels, characterized by their three-dimensional networks akin to biological tissues, are extensively utilized in artificial blood vessels, drug delivery, and nerve conduits due to their superior biocompatibility and fluid-transportation capacity. Nonetheless, the fabrication of hollow hydrogels presents significant challenges, including intricate steps, costly equipment, and structural instability. Consequently, refining the preparation techniques for hollow hydrogels remains paramount to surmounting the limitations of conventional methods. This research introduces an innovative approach that markedly diverges from traditional techniques, offering notable convenience and efficiency in the creation of hollow hydrogel structures. The central novelty of this method lies in employing laser light to induce an in situ photothermal effect, leading to the formation of hollow configurations. This laser-driven transformation of solid hydrogels into hollow structures addresses numerous shortcomings associated with traditional methods. For instance, conventional chemical approaches often necessitate several days to yield hollow hydrogels, and the resultant structures tend to be fragile and susceptible to damage under external pressure. In contrast, the laser-assisted technique facilitates the formation of hollow structures within 240 s, significantly outpacing traditional methods. To achieve controlled drug release, silk fibroin was integrated into the wall of the hollow hydrogels, enabling modulation of wall permeability and directing the drug release process.

Long-acting parenteral drug products are a popular choice for therapeutic areas requiring long term treatment. These products range from dispersed systems such as drug suspensions and polymeric microspheres to in situ forming polymeric implants. The lack of reliable drug release testing methods for these drug products not only impedes the development of new drug products but also affects generic drug development. Current release methods suffer from a range of problems such as high variability, poor reproducibility, poor discriminatory ability, lack of depot-like structure formation (that could mimic the in vivo situation). Moreover, shorter duration (less than a week) of release renders them unsuitable for in vitro-in vivo correlations (IVIVCs). To overcome these issues, novel adapters were developed for both USP-type-II & IV apparatus. These adapters were validated and assessed using the long-acting injectable (LAI) suspension drug product Depo Provera 150® as well as its Q1/Q2 equivalents. For USP-type-IV apparatus, two open adapter designs (conical and ellipsoidal shaped cavity with volume capacities of 50 µl and 1 ml, respectively) were developed. A closed conical adapter design with a volume capacity of 0.05 ml was developed for USP apparatus type-II. All three novel adapter designs effectively retained the suspensions, achieved release durations of 3-6 weeks with good reproducibility, minimal variability (RSD≤5%) and had good discriminatory ability. Based on this, the adapter-based dissolution methods were deemed suitable for IVIVC development of long-acting injectables. A successful Level A IVIVC was developed for Depo SubQ Provera 104® and its Q1Q2 equivalents using USP apparatus type IV with a conical adapter design. The closed adapter design for apparatus type-II was also investigated for suitability with risperidone in situ forming implants. The adapter was able to securely retain and maintain the shape of the in situ forming implants and resulted in release profiles of up to one month with good discriminatory ability and low standard error (RSD≤5%). These novel adapters hold promise of wide use for in vitro release testing of different long-acting parenteral drug products., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Nileshkumar Malavia, Quanying Bao, Diane J Burgess has patent pending to University of Connecticut. If there are other authors, they 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.)

Controlled drug release systems are pivotal in optimizing therapeutic outcomes and mitigating side effects in treatment protocols. While traditional delivery vectors such as liposomes, micro/nanoparticles, and microspheres are effective, they often struggle with consistency in drug release rates. This study addresses these issues by integrating stimuli-responsive elements specifically magnetic, thermal, and pH-responsive components into drug delivery systems for precise control. Central to our approach is the use of silk fibroin (SF), chosen for its superior biocompatibility and tunable degradation kinetics. We developed uniform carrier microspheres (CMs) by embedding polydopamine nanoparticles (PDA NPs) into SF microspheres using a custom-designed microfluidic platform. The development process and the application of this platform are detailed, highlighting the precision in control achievable. These CMs showcased enhanced photothermal effects, with the thermal response finely adjustable by altering the PDA NPs concentration, achieving a notable temperature increase of 24.5 ° C at 7.4 wt% concentration. High drug loading capacity (7.5%) and encapsulation efficiency (91.6%) were achieved, along with a pH-responsive release profile under near-infrared irradiation, paving the way for targeted anticancer drug delivery systems using the model drug doxorubicin hydrochloride. These findings underscore the potential of the developed CMs for external topical application, offering promising prospects for targeted cancer therapy utilizing drug-loaded microspheres., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

The azobenzene moiety is an intriguing structure that deforms under UV and visible light, indicating a high potential for biomedical applications. However, its reaction to UV radiation is problematic because of its high energy and low tissue penetration. Unlike previous research on azobenzene structures in photoresponsive materials, this study presents a novel method for imparting photostimulation-responsive properties to liposomes by incorporating the azobenzene moiety and extending the light wavelength with up-conversion nanoparticles. First, the azobenzene structure was incorporated into a phospholipid molecule to create Azo-PSG, which could spontaneously form vesicle assemblies in aqueous solutions and isomerizes within 1 h of light exposure. Furthermore, orthogonal up-conversion nanoparticles with a core-shell structure were created by sequentially growing lanthanide rare earths in the shell layer, which efficiently converts near-infrared light into ultraviolet (400 nm) and blue-green (540 nm) light. Combining these core-shell structured up-conversion nanomaterials with Azo-PSG molecules resulted in the creation of a near-infrared light-responsive smart nanoliposome system. Under near-infrared light irradiation, UCNPs emit UV and blue-green light, causing conformational changes in Azo-PSG molecules that allow drug release within 6 h. The reversible structural shift of Azo-PSG in response to light stimulation holds enormous promise for improving drug release techniques. This novel technique also expands the usage of UV-responsive compounds beyond their constraints of low penetration and high biotoxicity, allowing for rapid medication release under NIR light.

A series of hybrid hydrogels of poly(ethylene glycol) (PEG) were synthesized using gelatin as a crosslinker and investigated for controlled delivery of the first-generation cephalosporin antibiotic, Cefazedone sodium (CFD). A commercially available 4-arm-PEG-OH was first modified to obtain four-arm-PEG-succinimidyl glutarate (4-arm-PEG-SG), which formed the gelatin-PEG composite hydrogels (S n N m ) through crosslinking with gelatin. To regulate the drug delivery, S n N m hydrogels with various solid contents and crosslinking degrees were prepared. The effect of solid contents and crosslinking degrees on the thermal, mechanical, swelling, degradation, and drug release properties of the hydrogels were intensively investigated. The results revealed that increasing the crosslinking degree and solid content of S n N m could not only enhance the thermal stability, swelling ratio (SR), and compression resistance capacity of S n N m but also prolong the degradation and drug release times. The release kinetics of the S n N m hydrogels were found to follow the first-order model, suggesting that the transport rate of CFD within the matrix of hydrogels is proportional to the concentration of the drug where it is located. Specifically, S 1 N 1 -III showed 90% mass loss after 60 h of degradation and a sustained release duration of 72 h. The cytotoxicity assay using the MTT method revealed that cell viability rates of S 1 N 1 were higher than 95%, indicating excellent cytocompatibility. This study offers new insights and methodologies for the development of hydrogels as biomedical composite materials.

This study aims to design microgels for controlled drug release via enzymatically generated pH changes in the presence of glucose. Modern medicine is focused on developing smart delivery systems with controlled release capabilities. In response to this demand, we present the synthesis, characterization, and enzymatically triggered drug release behavior of microgels based on poly(acrylic acid) modified with glucose oxidase (GOx) (p(AA-BIS)-GOx). TEM images revealed that the sizes of air-dried p(AA-BIS)-GOx microgels were approximately 130 nm. DLS measurements showed glucose-triggered microgel size changes upon glucose addition, which depended on buffer concentration. Enzymatically triggered drug release experiments using doxorubicin-loaded microgels with immobilized GOx demonstrated that drug release is strongly dependent on glucose and buffer concentration. The highest differences in release triggered by 5 and 25 mM glucose were observed in HEPES buffer at concentrations of 3 and 9 mM. Under these conditions, 80 and 52% of DOX were released with 25 mM glucose, while 47 and 28% of DOX were released with 5 mM glucose. The interstitial glucose concentration in a tumor ranges from ∼15 to 50 mM. Normal fasting blood glucose levels are about 5.5 mM, and postprandial (2 h after a meal) glucose levels should be less than 7.8 mM. The obtained results highlight the microgel's potential for drug delivery using the enhanced permeability and retention (EPR) effect, where drug release is controlled by enzymatically generated pH changes in response to elevated glucose concentrations.

Stimulus-responsive systems allowing for the controlled release of drugs [...].

A major risk associated with surgery, including bone tissue procedures, is surgical site infection. It is one of the most common as well as the most serious complications of modern surgery. A helpful countermeasure against infection is antibiotic therapy. In the present study, a methodology has been developed to obtain clindamycin-modified polymer-ceramic hybrid composite coatings for potential use in bone regenerative therapy. The coatings were prepared using a UV-light photocrosslinking method, and the drug was bound to a polymeric and/or ceramic phase. The sorption capacity of the materials in PBS was evaluated by determining the swelling ability and equilibrium swelling. The influence of the presence of ceramics on the amount of liquid bound was demonstrated. The results were correlated with the rate of drug release measured by high-performance liquid chromatography (HPLC). Coatings with higher sorption capacity released the drug more rapidly. Scanning electron microscopy (SEM) imaging was carried out comparing the surface area of the coatings before and after immersion in PBS, and the proportions of the various elements were also determined using the EDS technique. Changes in surface waviness were observed, and chlorine ions were also determined in the samples before incubation. This proves the presence of the drug in the material. The in vitro tests conducted indicated the release of the drug from the biomaterials. The antimicrobial efficacy of the coatings was tested against Staphylococcus aureus . The most promising material was tested for cytocompatibility (MTT reduction assay) against the mouse fibroblast cell line L929 as well as human osteoblast cells hFOB. It was demonstrated that the coating did not exhibit cytotoxicity. Overall, the results signaled the potential use of the developed polymer-ceramic hybrid coatings as drug carriers for the controlled delivery of clindamycin in bone applications. The studies conducted were the basis for directing samples for further in vivo experiments determining clinical efficacy.

Azo switches are widely employed as essential components in light-responsive systems. Here, we develop an azo-fluorescent switch that is visible light-responsive and its light-responsive processes can be monitored using fluorescence imaging. Visible light irradiation promotes isomerization, accompanied by changes in fluorescence that enable the process to be monitored through fluorescence imaging. Furthermore, we document that the nanocavity size of liposome encapsulated nanoparticles containing azo changes in the isomerization process and show that this change enables construction of a light-responsive nanoplatform for optically controlled release of antimycotics. Also, natural light activation of nanoparticles of the switch loaded with an antimycotic agent causes death of Rhizoctonia solani. The results show that these nanoparticles can double the holding period in comparison to small molecule antimycotics. The strategy used to design the imaging-guided light-controlled nano-antimycotic release system can be applicable to protocols for controlled delivery of a wide variety of drugs., (© 2024. The Author(s).)

Transdermal drug delivery (TDD) is an attractive route of administration, providing several advantages, especially over oral and parenteral routes. However, TDD is significantly restricted due to the barrier imposed by the uppermost layer of the skin, the stratum corneum (SC). Microneedles is a physical enhancement technique that efficiently pierces the SC and facilitates the delivery of both lipophilic and hydrophilic molecules. Dissolving microneedles is a commonly used type that is fabricated utilizing various biodegradable and biocompatible polymers, such as polylactic acid, polyglycolic acid, or poly(lactide- co -glycolide) (PLGA). Such polymers also promote the prolonged release of the drug due to the slow degradation of the polymer matrix following its insertion. We selected carfilzomib, a small therapeutic peptide ( M W : 719.924 g/mol, log P 4.19), as a model drug to fabricate a microneedle-based sustained delivery system. This study is a proof-of-concept investigation in which we fabricated PLGA microneedles using four types of PLGA (50-2A, 50-5A, 75-5A, and 50-7P) to evaluate the feasibility of long-acting transdermal delivery of carfilzomib. Micromolding technique was used to fabricate the PLGA microneedles and characterization tests, including Fourier transform infrared spectroscopy, insertion capability using the skin simulant Parafilm model, histological evaluation, scanning electron microscopy, and confocal microscopy were conducted. In vitro release and permeation testing were conducted in vertical Franz diffusion cells. N -methyl pyrrolidone was utilized as the organic solvent and microneedles were solidified in controlled conditions, which led to good mechanical strength. Both in vitro release and permeation testing showed sustained profiles of carfilzomib over 7 days. The release and permeation were significantly influenced by the molecular weight of PLGA and the lipophilic properties of carfilzomib.

Nanocarriers for drugs have been investigated for decades, yet it is still challenging to achieve sustained release from nanomaterials due to drug loading inefficiency and burst release. In this study, we developed novel functional carbon dots (CDs) and investigated the therapeutic efficacy by studying the loading efficiency and release behavior of the anticancer drug doxorubicin (DOX). CDs were successfully synthesized using a one-step pyrolysis method with varying concentrations of citric acid (CA) and thiourea (TU). Functional groups, morphology, particle size, and zeta potential of synthesized CT-CDs and DOX loaded CT-CDs were investigated by UV-visible, Fluorescence, dynamic light scattering, Zeta Potential measurements, FTIR, and transmission electron microscopy. The zeta potential data revealed DOX loading onto CT-CDs by charge difference, i.e. -24.6 ± 0.44 mV (CT-CDs) and 20.57 ± 0.55 mV (DOX-CT-CDs). DOX was loaded on CDs with a loading efficiency of 88.67 ± 0.36%. In vitro drug release studies confirmed pH-dependent biphasic drug release, with an initial burst effect and sustained release of DOX was found to be 21.42 ± 0.28% (pH 5), 13.30 ± 0.03% (pH 7.4), and 13.95 ± 0.18% (pH 9) even after 144 h at 37 °C. The CT-CDs were non-toxic and biocompatible with L929 Fibroblasts cells. The cytotoxic effect of DOX-CT-CDs showed a concentration-dependent effect after 48 h with Glioblastoma U251 cells. Flow cytometry was used to examine the cellular uptake of CT-CDs and DOX-CT-CDs in L929 and U251 cells. It was observed that the maximum CT-CDs uptake was around 75% at the end of 24 h. This study showed that the synthesized fluorescent CT-CDs demonstrated a high drug loading capacity, pH-dependent sustained release of DOX, and high cellular uptake by mammalian cells. We believe this work provides practical and biocompatible CDs for chemotherapeutic drug delivery that can be applied to other drugs for certain therapeutic aims., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

The discovery of natural product-derived novel nanopesticide systems can effectively address the adverse effects caused by the improper use of traditional fungicides. In this research, 33 novel 3-carene-derived amide-thiourea derivatives 5a - 5zg were designed using laccase as the biological target, synthesized from natural renewable forest biomass resource 3-carene as the starting material, and structurally confirmed by Fourier-transform infrared spectroscopy, nuclear magnetic resonance, high-resolution mass spectrometry, and single crystal X-ray diffraction. The antifungal activity of the target compounds against eight plant pathogenic fungi was evaluated, and the results presented that target compound 5g exhibited excellent and broad-spectrum antifungal activity against the eight tested phytopathogenic fungi. Furthermore, the important contribution of the gem -dimethylcyclopropane structure in the antifungal activity of compound 5g was revealed through two negative controls without the gem -dimethylcyclopropane structure. Besides, compound 5g also demonstrated a prominent laccase inhibitory activity. The fluorescence quenching of the laccase with compound 5g , the chelating characteristics of compound 5g , and the interaction mode between the laccase and compound 5g presented that the target compound 5g probably exhibited excellent antifungal activity by acting on the laccase target. Cytotoxicity assay revealed that compound 5g had a low cytotoxicity for LO2 and HEK293T cell lines. On the other hand, to further improve the application potential of compound 5g , the 3-carene molecular skeleton containing gem -dimethylcyclopropane ring was grafted onto chitosan, and two nanopesticide carriers CACS and CATCS with sustained releasing performance were synthesized for loading compound 5g . 3-Carene-derived nanochitosan carrier CATCS showed a relatively regular, loose, and porous reticular structure, which displayed high dispersibility and good thermostability. In addition, this carrier had a higher drug-loading capacity and sustained releasing performance than that of the unmodified chitosan. This research identified that the target compound 5g could be used as a promising lead compound for fungicide against the laccase target, meanwhile, the complex 5g /CATCS deserved further study as a nanopesticide candidate.

Helicobacter pylori is the primary cause of gastric adenocarcinoma, which afflicts more than half of the world's population and seriously affects human health. However, achieving efficient treatment of H. pylori infection by effective drug delivery and bioavailability after oral administration remains a challenge due to the harsh microenvironment, short drug retention time, and physiological barriers in the stomach. Moreover, H. pylori has shown resistance to many clinical antibiotics. Antimicrobial peptides (AMPs) exhibit substantial therapeutic efficacy against H. pylori, while they are not likely to induce drug resistance, suggesting their potential utility for the treatment of diseases related to H. pylori . In this paper, we report the design and synthesis of an AMP (GE33) hydrogel with pH-responsive and controlled peptide release properties, in which the minimal inhibitory concentration of the AMP against H. pylori is as low as 1 μg/mL. GE33 self-assembles into a stable peptide hydrogel under neutral pH conditions but decomposes into monomers or oligomers under acidic conditions. Upon oral administration of the hydrogel, the acidic gastric environment would facilitate rapid release of active AMP molecules from the hydrogel and immediate targeting of H. pylori in the stomach wall. Additionally, the remaining peptide is protected in the hydrogel, extending its retention time in the stomach, so that persistent drug release is achieved. The controlled and sustained release manner of the active molecule GE33, which enhances drug bioavailability, along with its excellent bactericidal efficacy opens a great potential for treating H. pylori infection.

Quetiapine myristate (QM), an ester-bonded lipophilic prodrug of quetiapine (QTP), is synthesized and converted into an amphiphilic structure in acidic pH to trigger a novel self-assembled QM nanosuspension (QMN). Following injection, this QMN rearranges within physiological pH to form nanoaggregates in structure, resulting in enhanced physicochemical properties and in vivo therapeutic performance without an initial burst release. The 200-nm-sized QMN exhibits less invasive injection, higher drug content, and better storage stability profile than conventional poly(lactide-co-glycolide) (PLGA) nanosuspensions containing QTP or QM. Following a single intramuscular injection to beagle dogs (35 mg kg -1 QTP), QMN undergoes pH-responsive nanoaggregation to form the lipophilic prodrug, providing esterase-oriented sustained release for five weeks compared with the two-week period of PLGA nanosuspensions. Notably, QMN exhibits improved in vivo pharmacokinetic performance with long-acting delivery while minimizing issues associated with polymeric PLGA formulations, including the initial massive burst release, cellular toxicity, and adverse side effects. These results support the further development of QMN as a novel long-acting injectable to improve patient compliance and dosing frequency., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Herein, we reported novel docetaxel-decorated solid lipid nanoparticle (DCT-SLN)-loaded dual thermoreversible system (DCT-DRTS) for intramuscular administration with reduced burst effect, sustained release and improved antitumor efficacy. The optimized DCT-DRTs was subjected to in-vitro and in-vivo analyses. Antitumor evaluation of the DCT-DRTS was executed and compared with DCT-hydrogel, and DCT-suspension trailed by the histopathological and immune-histochemical analyses. The DCT-SLN gave a mean particle size of 157 nm and entrapment efficiency of 93 %. It was a solid at room temperature, and changed to liquid at physiological temperature due to its melting point of about 32 °C. Unlikely, poloxamer mixture remained liquefied at 25-27 °C, however converted to gel at physiological temperature. This behavior demonstrated opposed reversible property of the DCT-SLN and poloxamer hydrogel in DCT-DRTS system, making it ideal for intramuscular administration and quick gelation inside the body. The DCT-DRTS sustained the drugs release and unlike DCT-hydrogel, the preliminary plasma concentration of DCT-DRTS was significantly reduced, overcoming the burst release. A meaningfully enhanced antitumor efficacy and improved survival rate was observed from DCT-DRTS in tumor cell xenograft athymic nude mice. Additionally, increased apoptotic and reduced proliferation markers were observed in DCT-DRTS treated tumor masses. It was concluded that DCT-DRTS may be a suitable choice for intramuscular administration of DCT with sustained release, improved bioavailability, reduced toxicity and enhanced antitumor effects., 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.)

In addition to the solubilization of poorly water-soluble, highly lipophilic drugs, lipid nanoemulsions bear potential for drug targeting approaches. This requires that the drug remains within the emulsion droplets until they reach the site of action. Since drug release is rather controlled by the lipophilicity of the drug than by the formulation, this study systematically investigated the influence of drug lipophilicity on the course of drug transfer in (physiological) acceptor media. An increase in drug lipophilicity, according to ClogD/P values, was achieved by the formation of lipophilic prodrugs of 5-phenylanthranilic acid - a potential pathoblocker. The range of substances was supplemented by orlistat, lumefantrine and cholesteryl acetate as model drugs. Drug transfer from supercooled trimyristin nanodroplets was determined via differential scanning calorimetry by monitoring their onset crystallization temperature, which decreases linearly with increasing drug content. Release of the model (pro)drugs ranged from burst to hardly any release in the order of the ClogD/P values. Except for cholesteryl acetate, the results were in line with the lipophilicity of the model (pro)drugs estimated by their retention times on a reversed-phase HPLC column under isocratic conditions. An approximate prediction of drug release kinetics was, thus, possible by logP calculations and, to a limited extent, also by reversed-phase HPLC. A further finding was the increased drug loading capacity of the lipid nanoemulsion for lipophilic prodrugs, if the structural changes of the parent compound were accompanied by a lower melting point., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

In this study, a novel bio-composite material that allow sustained release of plant derived antimicrobial compound was developed for the biomedical applications to prevent the infections caused by microorganisms resistant to commercial antimicrobials agents. With this aim, bacterial cellulose (BC)-p(HEMA) nanocomposite film that imprinted with eugenol (EU) via metal chelated monomer, MAH was prepared. Firstly, characterization studies were utilized by FTIR, SEM and BET analysis. Then antimicrobial assays, drug release studies and in vitro cytotoxicity test were performed. A significant antimicrobial effect against both Gram (+) Staphylococcus aureus and Gram (-) Escherichia coli bacteria and a yeast Candida albicans were observed even in low exposure time periods. When antimicrobial effect of EU compared with commercially used agents, both antifungal and antibacterial activity of EU were found to be higher. Then, sustained drug release studies showed that approximately 55% of EU was released up to 50 h. This result proved the achievement of the molecular imprinting for an immobilization of molecules that desired to release on an area in a long-time interval. Finally, the in vitro cytotoxicity experiment performed with the mouse L929 cell line determined that the synthesized EU-imprinted BC nanocomposite was biocompatible.

The deterioration in the structure of thyroid hormones causes many thyroid-related disorders, which leads to a negative effect on the quality of life, as well as the change in metabolic rate. For the treatment of thyroid disorders, daily use of levothyroxine-based medication is essential. In the study, it is aimed to develop a polymeric nanocarrier that can provide controlled drug release of levothyroxine. In this respect, the p(HEMA-MAGA) nanopolymer was synthesized and then characterized by Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and Zeta size analysis. The specific surface area of the nanopolymer was calculated as 587.68 m 2 /g. The pH, temperature, concentration, and time parameters were determined for levothyroxine binding to p(HEMA-MAGA) and optimum binding was determined as pH 7.4, 25 °C, 25 µg/mL concentration, and 30 min adsorption time. As a result of the release performed at pH 7.4, a release profile was observed which increased for the first 3 days and continued for 14 days. According to the results of MTT cell viability analysis, it was determined that the p(HEMA-MAGA) nanopolymeric carrier system had no cytotoxic effect. This developed polymer-based nanocarrier system is suitable for long-term and controlled release of levothyroxine. This is a unique and novel study in terms of developing poly hydroxyethylmethacrylate-co-methacryloyl glutamic acid-based polymeric nanoparticles for levothyroxine release.

In this study, to address the defects of sodium alginate (SA), such as its susceptibility to disintegration, silica was coated on the outer layer of sodium alginate hydrogel beads in order to improve its swelling and slow-release properties. Tetraethyl orthosilicate (TEOS) was used as the hydrolyzed precursor, and the solution of silica precursor was prepared by sol-gel reaction under acidic conditions. Then SA-silica hydrogel beads prepared by ionic crosslinking method were immersed into the SiO 2 precursor solution to prepare SA-silica hydrogel beads. The chemical structure and morphology of the hydrogel beads were characterized by XRD, FTIR, and SEM, and the results showed that the surface of SA-silica beads was successfully encapsulated with the outer layer of SiO 2 , and the surface was smooth and dense. The swelling experiments showed that the swelling performance effectively decreased with the increase of TEOS molar concentration, and the maximum swelling ratio of the hydrogel beads decreased from 41.07 to 14.3, and the time to reach the maximum swelling ratio was prolonged from 4 h to 8 h. The sustained-release experiments showed that the SA-silica hydrogel beads possessed a good pH sensitivity, and the time of sustained-release was significantly prolonged in vitro. Hemolysis and cytotoxicity experiments showed that the SA-silica hydrogel beads were biocompatible when the TEOS molar concentration was lower than 0.375 M. The SA-silica-2 hydrogel beads had good biocompatibility, swelling properties, and slow-release properties at the same time.

Hydrophilic and hydrophobic modified nanomicelles might be more conducive to passage of the gastrointestinal barrier than walnut peptide (WP). In this study, a novel double modified starch polymer, SB-CST-DCA, was synthesized by grafting sulfabetaine (SB) and deoxycholic acid (DCA) onto corn starch (CST) molecules through etherification and esterification. The modification mechanism was discussed to determine its chemical structure, morphological properties, and thermal stability. Peptide-loaded nanomicelles (SB-CST-DCA-WP) were prepared using WP as the core material. The encapsulation efficiency and peptide loading amount reached 76.90 ± 1.52% and 18.27 ± 0.53%, respectively, with good stability and pH-responsive release behavior observed to effectively control WP release and enhance its antioxidant activity. The composite exhibited safety, non-toxicity, and good blood compatibility at concentrations below 125 μg/mL. Duodenum was identified as the main absorption site with an absorption ratio of 41.16 ± 0.36%., 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.)

Plants require essential nutrients to grow, which soil alone cannot provide. Chemical fertilizers like urea supply the necessary nutrients, including nitrogen. They quickly dissolve in water and can contaminate it with nitrate and nitrite, which can cause diseases. Slow-release fertilizers are a better option to reduce environmental risks. Researchers are exploring cheap and biodegradable alternatives, such as lignin. A critical discussion in the coated urea fertilizer is modeling the nitrogen diffusion process in the coating, which predicts the system's behavior. This article uses lignin sulfonate to coat urea fertilizer, which should first be acetylated with decanoyl chloride. One of the critical parameters is the diffusion coefficient (D). D is determined using the mass transfer flux and the completion time of the effective substance, and with its help, the graph of the total mass transferred from the membrane in a specific time (M t ) is determined. D equals 6.298813 × 10 -8  cm 2 /s using the time lag method. Also, with the fixed-point convergence method, 5.8849 × 10 -8  cm 2 /s was obtained, which has about 0.80 % error with the D obtained by the time lag method. The M t obtained from the analytical method and the experimental data coincides with a minimal error, which indicates high accuracy., 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.)

Infectious wounds occur when harmful microorganisms such as bacteria or viruses invade a wound site. Its problems associated include delayed healing, increased pain, swelling, and the potential for systemic infections. Therefore, developing new wound dressing materials with antibacterial effects is crucial for improving the healing process. Here a redox-degradable hydrogel loaded with an antibacterial peptide (vancomycin) in a straightforward gram-scale synthesis, is developed. The hydrogel structure consists of a disulfide bond-containing hyperbranched polyglycerol (SS-hPG) that is cross-linked by 4-arm polyethylene glycol-thiol (4-arm PEG-SH). The polymerization mechanism and full characterization of SS-hPG are described as this synthesis is reported for the first time. Rheology is used to ascertain the hydrogel's mechanical characteristics, such as stiffness, and self-healing, determining these properties for different ratios and concentrations of both gel components. The incorporation of disulfide bonds in the hydrogel is proved by conducting degradation experiments in reductive environments. Fluorescein isothiocyanate-albumin (FITC-BSA) and vancomycin both are loaded into the gel, and the guest release kinetics is assessed for both slow and on-demand releases. Finally, the in vitro and in vivo experiments prove that the vancomycin-loaded hydrogel acts as an antibacterial barrier for wound dressing and accelerates the healing of infectious wounds in a mouse model., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Drug delivery in transplantation plays a vital role in promoting graft survival, preventing rejection, managing complications, and contributing to positive patient outcomes. Targeted and controlled drug delivery can minimize systemic effects. Thermosensitive hydrogels, due to their unique sol-gel transition properties triggered by thermo-stimuli, have attracted significant research interest as a potential drug delivery system in transplantation. This review describes the current status, characteristics, and recent applications of thermosensitive hydrogels for drug delivery. Studies aimed at improving allotransplantation outcomes using thermosensitive hydrogels are then elaborated on. Finally, the challenges and opportunities associated with their use are discussed. Understanding the progress of research will serve as a guide for future improvements in their application as a means of targeted and controlled drug delivery in translational therapeutic applications for transplantation., (© 2024 Wiley‐VCH GmbH.)

Bacterial infections and the degeneration of the capillary network comprise the primary factors that contribute to the delayed healing of diabetic wounds. However, treatment modalities that cater to effective diabetic wounds healing in clinical settings are severely lacking. Herein, a dual-functional microsphere carrier was designed, which encapsulates polyhexamethylene biguanide (PHMB) or recombinant human vascular endothelial growth factor (rhVEGF) together. The in vitro release experiments demonstrated that the use of the microspheres ensured the sustained release of the drugs (PHMB or rhVEGF) over a period of 12 days. Additionally, the integration of these controlled-release microspheres into a dermal scaffold (DS-PLGA@PHMB/rhVEGF) imbued both antibacterial and angiogenic functions to the resulting material. Accordingly, the DS-PLGA@PHMB/rhVEGF scaffold exhibited potent antibacterial properties, effectively suppressing bacterial growth and providing a conducive environment for wound healing, thereby addressing the drawbacks associated with the susceptibility of rhVEGF to deactivation in inflammatory conditions. Additionally, the histological analysis revealed that the use of the DS-PLGA@PHMB/rhVEGF scaffold accelerated the process of wound healing by inhibiting inflammatory reactions, stimulating the production of collagen formation, and enhancing angiogenesis. This provides a novel solution for enhancing the antibacterial and vascularization capabilities of artificial dermal scaffolds, providing a beacon of hope for improving diabetic wound healing., 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 key strategy in enhancing the efficacy of collagen-based hydrogels involves incorporating polysaccharides, which have shown great promise for wound healing. In this study, semi-interpenetrating polymeric network (semi-IPN) hydrogels comprised of collagen (Col) with the macrocyclic oligosaccharide β-cyclodextrin (β-CD) (20-80 wt.%) were synthesised. Fourier-transform infrared (FTIR) spectroscopy confirmed the successful fabrication of these Col/β-CD hydrogels, evidenced by the presence of characteristic absorption bands, including the urea bond band at ∼1740 cm -1 , related with collagen crosslinking. Higher β-CD content was associated with increased crosslinking, higher swelling, and faster gelation. The β-CD content directly influenced the morphology and semi-crystallinity. All Col/β-CD hydrogels displayed superabsorbent properties, enhanced thermal stability, and exhibited slow degradation rates. Mechanical properties were significantly improved with contents higher than β-CD 40 wt.%. These hydrogels inhibited the growth of Escherichia coli bacteria and facilitated the controlled release of agents, such as malachite green, methylene blue, and ketorolac. The chemical composition of the Col/β-CD hydrogels did not induce cytotoxic effects on monocytes and fibroblast cells. Instead, they actively promoted cellular metabolic activity, encouraging cell growth and proliferation. Moreover, cell signalling modulation was observed, leading to changes in the expression of TNF-α and IL-10 cytokines. In summary, the results of this research indicate that these novel hydrogels possess multifunctional characteristics, including biocompatibility, super-swelling capacity, good thermal, hydrolytic, and enzymatic degradation resistance, antibacterial activity, inflammation modulation, and the ability to be used for controlled delivery of therapeutic agents, indicating high potential for application in advanced wound dressings.

Background: Cancer is a serious threat to human life, health and social development. In recent years, nanomicelles, as an emerging drug carrier material, have gradually entered people's field of vision because of their advantages of improving bioavailability, maintaining drug levels, reducing systemic side effects and increasing drug accumulation at target sites. Methods: In this study, B-GPSG nano-micelles were prepared by film dispersion hydration method using brucine as model drug and glycyrrhetinic acid-polyethylene glycol-3-methylene glycol-dithiodipropionic acid-glycerol monostearate polymer as nano-carrier. The preparation process, characterization, drug release in vitro, pharmacokinetics and liver targeting were investigated. Results: The results showed that the range of particle size, polydispersion index and Zeta potential were 102.7 ± 1.09 nm, 0.201 ± 0.02 and -24.5 ± 0.19 mV respectively. The entrapment efficiency and drug loading were 83.79 ± 2.13% and 12.56 ± 0.09%, respectively. The drug release experiments in vitro and pharmacokinetic experiments showed that it had obvious sustained release effect. For pharmacokinetics study, it shows that both the B-GPSG solution group and the B-PSG solution group changed the metabolic kinetic parameters of brucine, but the B-GPSG solution group had a better effect. Compared with the B-PSG solution group, the drug was more prolonged in rats. The half-life in the body and the retention time in the body of B-GPSG are more helpful to improve the bioavailability of the drug and play a long-term effect. The tail vein injection results of mice indicate that B-GPSG can target and accumulate brucine in the liver without affecting other key organs. Cell uptake experiments and tissue distribution experiments in vivo show that glycyrrhetinic acid modified nano-micelles can increase the accumulation of brucine in hepatocytes, has a good liver targeting effect, and can be used as a new preparation for the treatment of liver cancer. Conclusion: The B-SPSG prepared in this experiment can provide a new treatment method and research idea for the treatment of liver cancer., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Mesoporous silica microspheres (MSMs) possess poor biocompatibility. This study focuses on integrating MSMs with polymers to obtain hybrid materials with superior performance compared to the individual components and responsive release in specific environments. The synthesized MSMs were aminated, and subsequently, soybean hull polysaccharide (SHPs) was modified onto MSMs-NH 2 to produce MSMs-NH 2 @SHPs nanoparticles. The encapsulation rate, loading rate of curcumin (Cur), and in vitro release behavior were investigated. Results indicated that the encapsulation efficiency of Cur by MSMs-NH 2 @SHPs nanoparticles reached 75.58%, 6.95 times that of MSMs-NH 2 with a load capacity of 35.12%. It is noteworthy that these nanoparticles exhibit pH-responsive release capacity in vitro. The cumulative release rate of the three nanoparticles at pH 5.0 was higher than that at pH 7.4. MSMs-NH 2 @SHPs had a cumulative release rate of 56.55% at pH 7.4, increasing to 76.21% at pH 5.0. In vitro experiments have shown that MSMs-based nanoparticles have high delivery efficiency and can achieve pH-sensitive drug release, with a high release rate in a slightly acidic acid, highlighting the potential for controlled release of Cur., 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.)