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Choroidal neovascularization (CNV) represents a hallmark of neovascular fundus diseases, including age-related macular degeneration and diabetic retinopathy. Traditional eyedrops have encountered formidable challenges in treating CNV, primarily due to their extremely poor intraocular bioavailability and potential adverse off-target effects. Herein, an ocular-permeable supramolecular prodrug eyedrop (Di-DAS/P-PCD) has been developed for the on-demand delivery of antiangiogenic agents in the oxidative microenvironment of CNV. The eyedrop nanoformulation is composed of cell-penetrating peptide-modified PEGylated cyclodextrin (P-PCD) and reactive oxygen species (ROS)-sensitive antiangiogenic dasatinib prodrug Di-DAS. In a laser-induced CNV mouse model, daily instillation of Di-DAS/P-PCD has achieved remarkable penetration into the choroid and significantly suppressed CNV growth while exhibiting a good biocompatibility profile. Our results highlight the potential of the supramolecular prodrug eyedrops as a versatile approach for the targeted treatment of CNV and other neovascular eye disorders.

Background: Solid phase extraction (SPE) is a standard sample preparation technique in HPLC workflows. Inline cartridges are high-performance alternatives to manual or robotic systems but at long term, they suffer from irreversible sorption of matrix components and sorbent compaction. Bead injection (BI) is a niche fluidic technique that allows renewing a sorbent bed through the manipulation of its suspension. However, there is a need for a versatile and reliable tool in HPLC that can exchange the inline sorbent automatically, resorting to inexpensive and assorted bulk sorbents., Results: We present a new flow path for a liquid chromatographic injector to perform inline micro-solid phase extraction. The sample is processed at real time, trapping the analytes and discarding the matrix. Cleaning the matrix and injecting 10 μL of sample takes 70 s, comparable with the injection in commercial HPLC systems. If the aim is to preconcentrate the analytes, average enrichment factors of 250 have been obtained after processing sample volumes of 3200 μL in 16 min (interleavable with the chromatographic step), keeping the peak position and width independent of the injected volume (compared to large volume direct injection). The desired bed mass is automatically and pressure-driven manipulated in the valve, retained by an inline frit, and optionally, after the analysis, removed by forward flow. The chromatographic performance of the new design is compared to the standard 6-port, 2-position HPLC injector. As a case study, we have monitored the extraction kinetics of a cyclodextrin-based bioaccessibility extraction test of persistent organic contaminants in soil, by extracting several fractions in valve, process them with inline SPE with a balanced hydrophilic-hydrophobic reversed-phase sorbent, and inject the bioaccessible compounds into HPLC. Aiming at avoiding carryover, the sorbent bed (ca. 3 mg) is exchanged before every run. It should be noted that this contribution focuses on HPLC, but other non-separative techniques, such as Flow Injection Analysis, can equally benefit from this injection platform., Significance: This contribution reports the first use of inline BI-solid phase extraction in HPLC workflows, without heart-cut eluate injection, in which the sorbent can be exchanged automatically by forward flow. This performance is enabled by prototyping a valve that can autonomously swap sorbents in real-time for diverse samples, as a cartridge exchanger, but using cost-effective and environmentally friendlier bulk sorbents (bed masses from sub-mg to 5 mg) without requiring additional hardware., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: David J. Cocovi-Solberg reports equipment, drugs, or supplies was provided by Wacker Chemie AG. 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 The Authors. Published by Elsevier B.V. All rights reserved.)

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.)

Biological nanopores are increasingly used in molecular sensing due to their single-molecule sensitivity. The detection of per- and polyfluoroalkyl substances (PFAS) like perfluorooctanoic acid and perfluorooctane sulfonic acid is critical due to their environmental prevalence and toxicity. Here, we investigate selective interactions between PFAS and four cyclodextrin (CD) variants (α-, β-, γ-, and 2-hydroxypropyl-γ-CD) within an α-hemolysin nanopore. We demonstrate that PFAS molecules can be electrochemically sensed by interacting with a γ-CD in a nanopore. Using HP-γ-CDs with increased steric resistance, we can identify homologs of the perfluoroalkyl carboxylic acid and the perfluoroalkyl sulfonic acid families and detect common PFAS in drinking water at 0.4 to 2 parts per million levels, which are further lowered to 400 parts per trillion by sample preconcentration. Molecular dynamics simulations reveal the underlying chemical mechanism of PFAS-CD interactions. These insights pave the way toward nanopore-based in situ detection with promises in environmental protection against PFAS pollution.

Cyclodextrin-based stationary phases are important chiral selectors in liquid chromatography. These chiral selectors are most commonly used in the reversed-phase mode because native cyclodextrin assumes a torus conformation with a hydrophobic cavity, facilitating inclusion complexation in aqueous environments. However, the value of native and aliphatic-derivatized cyclodextrins in other modes, such as the normal phase liquid chromatography (NPLC) or super/subcritical fluid chromatography (SFC), remains unexplored. In this work, we report chiral separations of pharmaceutically relevant compounds with the 1,4-dihydropyridine (DHP) scaffold on a 2-hydroxypropyl-β-cyclodextrin (CD-RSP) stationary phase in NPLC and SFC modes. Although CD-RSP is conventionally considered only effective in the reversed-phase mode, we show that these compounds tend to separate better in other modes. This is particularly apparent for analytes with hydrogen-bonding moieties. We propose that the separation mechanism primarily depends on external adsorption rather than inclusion complexation. The negligible impact of a complexation-competitive additive on retention in non-aqueous modes further supports this claim. Additionally, van Deemter analysis demonstrated the efficiency and environmental benefit of using this stationary phase in the SFC mode, further highlighting the promise of aliphatic derivatized cyclodextrin stationary phases for greener separations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Daniel W. Armstrong has a potential research conflict of interest due to a financial interest with the company AZYP, LLC. A management plan has been created to preserve objectively in research in accordance with UTA policy, (Copyright © 2024. Published by Elsevier B.V.)

Melanoma is an aggressive skin cancer notorious for high levels of drug resistance. Additionally, current treatments such as immunotherapies are often associated with numerous adverse side effects. The use of nitric oxide (NO) may represent an attractive treatment for melanoma due to NO's various anticancer properties, unlikeliness to foster resistance, and limited toxicity toward healthy tissues. The anticancer effects of chemical NO donors have been explored previously but with limited understanding of the needed characteristics for exerting optimal antimelanoma activity. Herein, the in vitro therapeutic efficacy of three macromolecular NO donor systems (i.e., cyclodextrin, mesoporous silica nanoparticles, and hyaluronic acid) with tunable NO-release kinetics was explored by evaluating skin permeation along with toxicity against melanoma and healthy skin cells. Cytotoxicity against melanoma cells was dependent on NO payload and not donor identity or NO-release kinetics. In contrast, cytotoxicity against healthy cells was primarily influenced by the macromolecular NO donor, with cyclodextrin- and hyaluronic acid-based NO donors having the highest therapeutic indices. In vitro skin permeation was influenced by both the size and charge of the NO donor, with smaller, more neutral donors resulting in greater permeation. A Pluronic F127 organogel was optimized for the delivery of a cyclodextrin-based NO donor. Delivery of the NO donor in this manner resulted in increased in vitro skin permeation and reduced tumor growth in an in vivo model.

Cyclodextrins (CDs) belong to a class of cyclic oligosaccharides characterized by their toroidal shape consisting of glucose units linked via α-1,4-glycosidic bonds. This distinctive toroidal shape exhibits a dual nature, comprising a hydrophobic interior and a hydrophilic exterior, making CDs highly versatile in various pharmaceutical products. They serve multiple roles: they act as solubilizers, stabilizers, controlled release promoters, enhancers of drug bioavailability, and effective means of masking undesirable tastes and odors. Taking advantage of these inherent benefits, CDs have been integrated into numerous nanoscale drug delivery systems. The resulting nanomaterials exploit the exceptional properties of CDs, including their ability to solubilize hydrophobic drugs for substantial drug loading, engage in supramolecular complexation for engineered nanomaterials, increase bioavailability for improved therapeutic efficacy, stabilize labile drugs, and exhibit biocompatibility and versatility. This paper compiles recent studies on CD functional nanoscale drug delivery platforms. First, we described the physicochemical and toxicological aspects of CDs, CD/drug inclusion complexation, and their impact on improving drug bioavailability. We then summarized applications for CD-functional nano delivery systems based on polymeric, hybrid, lipid-based nanoparticles, and CD-based nanofibers. Particular interest was in the targeted applications and the function of the CD molecules used. In most applications, CD molecules were used for drug solubilization and loading, while in some studies, CD molecules were employed for supramolecular complexation to construct nanoscale drug delivery systems. Finally, the review concludes with a thoughtful consideration of the current challenges and outlook., (© 2024 Wiley Periodicals LLC.)

The acceptance of nonconventional solvents as viable substitutes for traditional organic solvents has been widely recognized in order to comply with food-safety and sustainability regulations. Cyclodextrins (CDs), derived from starch, are cyclic oligosaccharides with the ability to form inclusion complexes with a variety of functional substances as the result of their distinctive structure, which enables them to effectively encapsulate bioactive compounds, rendering them highly sought after for use in food applications. In the implementing plan to achieve carbon-neutral emissions by 2050, the novel generation of supramolecular deep eutectic solvents (SUPRADES) has garnered increased attention and interest. The approach of utilizing SUPRADES as emerging solvents was just beginning to be applied to food studies. This review summarizes a revision of the current advances and critical evaluation of cyclodextrin-based SUPRADES (CD-based SUPRADES) as promising solvents for the enhancement of the extraction efficiency, solubilization and stability of bioactive compounds, adsorption and separation of food components, packaging materials, and modification of biopolymers. To meet the sustainable processing needs of the food industry, the emerging categories of CD-based SUPRADES need to be further fabricated. Herein, our review will sort out the potential application of CD-based SUPRADES in the food industry, aiming to provide a better understanding of CD-based SUPRADES within the viewpoint of food science. Formulation intricacies and scalability issues in real functional foods using CD-based SUPRADES as media need more efforts., (© 2024 Institute of Food Technologists®.)

Glycosylation is an effective way to promote the total intake of polyphenols in humans by increasing the solubility of polyphenols. In this study, an efficient glycosylation system was built via the dynamic complexation of CD with polyphenols and synchronous coupling reaction with cyclodextrin glycosyltransferase (CGTase) in water. The glycosylation efficiencies of quercetin, naringenin, rutin, resveratrol and caffeic acid were 20.9, 3.6, 2.7, 3.4 and 1.5 times higher than the non-complexed system. To quantify conversion rate and determine the rate-limiting step, the mixed product was treated with amyloglucosidase to obtain α-glucosyl rutin, which was identified as rutin 4"-O-α-D-glucopyranoside with purity of 93.6 % and yield of 34.8 % from NMR, MS and HPLC analysis. The results of half-reaction kinetics showed that the catalytic efficiencies of ring-opening of γ-CD (k 1 ) and glycosylation reaction of rutin (k 2 ) were 621.92 and 9.43 mM -1 ·s -1 . The rate-limiting step was clarified for the first time, showing that the ring-opening ability of CGTase to CD was much higher than its glycosylation ability to polyphenols. It is speculated that the rapid ring-opening reaction of CD affected its dynamic complexation, releasing many polyphenols which were not utilized by CGTase in time. Therefore, adjusting the ratio and concentration of CD resulted in an optimal glycosylation molar yield of 84.1 % for rutin, which was the highest yield reported so far in water. This study established a universal system and clarified the rate-limiting step in the enzymatic glycosylation, providing theoretical guidance for efficient production of polyphenol glycosylation., 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 patients with diabetes, chronic hyperglycemia impairs immune function at wound sites, increasing susceptibility to infections, prolonging inflammation, and delaying healing. This study aimed to develop wound dressings that control bacterial infections and accelerate healing. Phloretin (PHL), which has antibacterial and anti-inflammatory properties, was encapsulated with γ-cyclodextrin (γ-CD) to form a PHL@CD complex with enhanced bioavailability. This complex was incorporated into nanofiber wound dressings composed of polycaprolactone and natural silk protein. The resulting dressings exhibited favorable physical and chemical properties, including nutrient transport and gas exchange, which are essential for wound healing. The nanofiber membranes exhibited antibacterial activity against Staphylococcus aureus (90.31 ± 4.41 % inhibition), with high antioxidant capacity (91.48 ± 0.33 % ABTS scavenging) and blood compatibility. The membranes also promoted cell viability. Importantly, the nanofiber dressings accelerated wound healing in a diabetic mouse model by reducing the duration of inflammation. The novel nanofiber wound dressing can significantly improve the treatment of 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.)

Cyclodextrin (CD) derivatives have recently gained worldwide attention, which have versatile advantages and restrained the defects of parent CDs. The superior properties of CD derivatives in encapsulation, stabilization, and solubilization facilitate their application in food, biomedicine, daily chemicals, and textiles. In this review, the preparation, classification, and main benefits of CD derivatives are systematically introduced. By introducing targeted groups into the parent CD molecule, they exhibit significant improvement in their required characteristic. Besides, the important point closely related to application, the safety assessment, has also been highlighted. Most tested CD derivatives have been verified to be relatively safe in a limited dosage. Then, the applications of CD derivatives have been described in detail from the food to its related field. In food field, CD derivatives play an important role in the stability and bioavailability of bioactive compounds, control flavor release, and improve the antimicrobial and antioxidant properties of packaging materials. These advantages can also be expanded to the related field, offering innovative solutions that enhance product quality, human health, and environmental sustainability. This review highlights the broad applications and potential of CD derivatives, underscoring their role in driving advancements across multiple industries., 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.)

Background: Chemiluminescence (CL) bioassay is one of the most advanced and used detection method in clinical diagnosis and biomedical research because of the advantages of low background, easy operation, and wide-field imaging without a light source or microscope. The luminol/hydrogen peroxide/horseradish peroxidase (luminol/H 2 O 2 /HRP) system is the most popular CL system, but its application in high-throughput imaging detection is challenged due to its low luminescence efficiency and flash-type emission which is difficult in ensuring the reproducibility and consistency of detection results., Results: We reported a glow-type CL system of luminol@CD/H 2 O 2 /HRP by using a supramolecular enhancer of cyclodextrin (CD). This luminol@CD/H 2 O 2 /HRP system exhibited a luminescence lifetime of 41 min for sensitive and accurate imaging analysis. The long-lasting CL emission was attributed to the formation of a 1:1 host-guest complex between luminol and CD, which could stabilize the emitter and effectively reduce nonradiative relaxation. The formation of luminol@CD complex was determined through NMR experiments and theoretical analysis. Under optimum conditions, the luminol@CD/H 2 O 2 /HRP system showed higher sensitivity and much better precision than classical luminol/H 2 O 2 /HRP system for imaging detection of HRP. Especially, this glow-type luminol@CD/H 2 O 2 /HRP system realized CL imaging of microwell arrays on microfluidic chips. In addition, the luminol@CD/H 2 O 2 /HRP system was successfully applied for point-of-care detection of 17β-estradiol based on a competitive mechanism of host-guest recognition., Significance: An efficient CL system is crucial for obtaining reproducible and consistent results for accurate detection. Our luminol@CD/H 2 O 2 /HRP system emitted strong and persistent luminescence, resulting in reliability and efficiency at both CL macroscopic and microscopic imaging detection. We expected the luminol@CD/H 2 O 2 /HRP CL system to be applied in various detection 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.)

This study investigated the efficacy of a new chrysin-loaded calixarene-cyclodextrin ternary drug delivery system (DDS) in reversing liver fibrosis in a mouse model of chronic diabetes. The system was designed to enhance the solubility and bioavailability of chrysin (CHR) and calixarene 0118 (OTX008). Adult male CD1 mice received streptozotocin (STZ) injections to induce diabetes. After 20 weeks, they underwent intraperitoneal treatments twice weekly for a two-week period. Histological analyses revealed that long-term hyperglycaemia increased liver fibrosis and altered hepatic ultrastructure, characterized by lipid accumulation, hepatic stellate cell activation, and collagen deposition. The treatment with the chrysin-loaded DDS restored liver structure closely to normal levels, as opposed to the minimal impact observed with sulfobutylated β-cyclodextrin (SBECD) alone. The treatment significantly decreased serum activities of alanine /aspartate transaminases and reduced the gene expression of collagen type I (Col-I). It also modulated the transforming growth factor beta 1 (TGF-β1)/Smad signalling pathway, inhibiting the activation and proliferation of hepatic stellate cells. The treatment led to a downregulation of the TGF-β1 gene and its receptors TGFβR1 and TGFβR2, together with a decrease in Smad 2 and 3 mRNA levels. Conversely, Smad 7 mRNA expression was increased by the DDS. Furthermore, it downregulated galectin-1 (Gal-1) gene and protein levels, which correlated with fibrotic markers. In conclusion, the chrysin-loaded calixarene-cyclodextrin ternary DDS presents a promising therapeutic approach for diabetic liver fibrosis, effectively targeting fibrotic pathways and restoring hepatic function and structure., 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 Inc.)

Although charge-converting nanoparticles (NPs) potentially penetrate tumours deeply, conventional charge conversion strategies possess limitations, including low selectivity and slow, inconsistent conversion rate within the tumour microenvironment. In this study, we synthesized a zwitterionic near-infrared cyclodextrin derivative of heptamethine cyanine and complexed it with pheophorbide-conjugated ferrocene to produce multifunctional theranostic nanotherapeutics. Our NPs demonstrated enhanced tumour-targeting ability, enabling the highly specific imaging of rectal tumours, with tumour-to-rectum signal ratios reaching up to 7.8. The zwitterionic surface charge of the NPs was rapidly converted to a cationic charge within the tumours on 880 nm near-infrared laser irradiation, promoting the tumoural penetration of NPs via transcytosis. After penetration, photodynamic/chemodynamic therapy was initiated using a 660 nm laser. Our NPs eradicated clinically relevant-sized heterotopic tumours (~250 mm 3 ) and orthotopic rectal tumours, displaying their potential as theranostic nanoplatforms for targeting rectal cancer., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Cyclodextrins are enabling pharmaceutical excipients that solubilize and stabilize drugs in aqueous formulations. Cyclodextrins possess very favorable pharmacokinetic and toxicological profiles and are commonly used in marketed drug products for oral and parenteral administration. However, their use in ophthalmic products is still very limited. Cyclodextrins have a broad range of physical properties that are specifically appropriate for designing topical ophthalmic dosage forms. Additionally, both the regulatory and intellectual property environments have been cleared over the last years and should foster their use for designing new drugs for ophthalmic use., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

A cation channel possessing cascaded hydrated acid groups has been successfully constructed using pillar[5]arene integrated with dual cyclodextrins. As a proof-of-concept, the secondary side of cyclodextrin substituted by 24 -CO 2 H groups presents high coordination sites, which helps hydrated cations to quickly dehydrate and accelerates efficient cation transport (Rb + > Cs + > K + > Na + > Li + ). Notably, benefitted by the protonation and deprotonation of -CO 2 H groups, ion permeation activity of the channel molecules under acidic condition (pH = 6.0) is 2.8 times higher than that under alkaline conditions (pH = 8.0), exhibiting pH-modulated property and promising potential in building intelligent artificial ion channels with customized features.

Starch is extensively used across various fields due to its renewable properties and cost-effectiveness. Nonetheless, the high viscosity that arises from gelatinization poses challenges in the industrial usage of starch at high concentrations. Thus, it's crucial to explore techniques to lower the viscosity during gelatinization. In this study, large-ring cyclodextrins (LR-CDs) were synthesized from potato starch (PS) by using 4-α-glucanotransferase and then added to PS to alleviate the increased viscosity during gelatinization. The results from rapid viscosity analyzer (RVA) demonstrated that the inclusion of 5 % (w/w) LR-CDs markedly reduced the peak viscosity (PV) and final viscosity (FV) of PS by 49.85 % and 28.17 %. In addition, there was a quantitative relationship between PV and LR-CDs. The equation was fitted as y = 2530.73×e -x/2.48 +1832.79, which provided a basis for the regulation of PS viscosity. The mechanism of LR-CDs reducing the viscosity of PS was also studied. The results showed that the addition of LR-CDs inhibited the gelatinization of PS by enhancing orderliness and limiting water absorption, resulting in a decrease in viscosity. This study provides a novel method for reducing the viscosity of starch, which is helpful for increasing its concentration and reducing energy consumption in industrial applications., 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.)

Cyclodextrins (CDs) are ubiquitous excipients, constituted of cyclic glucopyranose units, and possess a unique dual nature, that of a hydrophobic interior and a hydrophilic exterior. This enables their interaction with lipid-affinitive compounds and hydrophilic compounds, thereby augmenting their application in pharmaceutical formulations as agents for improving solubility, as well as fundamental elements of advanced drug delivery systems. Additionally, CDs, upon suitable modification, can strategically participate in the interaction with cellular components and physical barriers, such as the blood-brain barrier, where their intricate and multifunctional engagement leads to various biological impacts. This review consolidates the crucial features of CDs and their derivatives, and summarizes the applications of them as drug delivery systems in neurodegenerative disorders, emphasizing their notable potentials.

Cyclodextrin (CD) derivatives have gained significant attention in biomedical applications due to their remarkable biocompatibility, unique inclusion capabilities, and potential for functionalization. This review focuses on recent advancements in CD-based assemblies, specifically their role in improving drug delivery, emphasizing remdesivir (RMD). The review introduces CD materials and their versatile applications in self-assembly and supramolecular assembly. CD materials offer immense potential for designing drug delivery systems with enhanced activity. Their inherent inclusion capabilities enable the encapsulation of diverse therapeutic agents, including RMD, resulting in improved solubility, stability, and bioavailability. The recent advances in CD-based assemblies, focusing on their integration with RMD have been concentrated here. Various strategies for constructing these assemblies are discussed, including physical encapsulation, covalent conjugation, and surface functionalization techniques. Furthermore, exploring future directions in these fields has also been provided. Ongoing research efforts are directed toward developing novel CD derivatives with enhanced properties, such as increased encapsulation efficiency and improved release kinetics. Moreover, the integration of CD-based assemblies with advanced technologies such as nanomedicine and gene therapy holds tremendous promise for personalized medicine and precision therapeutics.

Kidney dysfunction leads to the retention of metabolites within the blood that are not effectively cleared with conventional hemodialysis. Magnetic nanoparticle (MNP)-based absorbents have inherent properties that make them amenable to capturing toxins in the blood, notably a large surface area that can be chemically modified to enhance toxin capture and the ability to be easily collected from the blood using an external magnetic field. Cyclodextrins (CDs) present a chemical structure that facilitates the binding of small molecules. However, the hemocompatibility of MNPs modified with films composed of different native types of CDs (α, β, or γ) has not yet been investigated, which is information crucial to the potential clinical application of MNPs to supplement hemodialysis. To this end, films of α-, β-, or γ-CDs were formed on MNPs and characterized. The impact of these films on the adsorbed protein structure, composition of key adsorbed proteins, and clotting kinetics were evaluated. It was found that modified MNPs did not significantly affect the secondary structure of some proteins (albumin, lysozyme, α-lactalbumin). The adsorbed proteome from platelet-poor human plasma was evaluated as a function of film properties. Compared to non-modified nanoparticles, CD-modified MNPs exhibited a significant decrease in the adsorbed protein per surface area of MNPs. The immunoblot results showed variations in the adsorption levels of C3, fibrinogen, antithrombin, Factor XI, and plasminogen across CD-modified MNPs. The hemocompatibility experiments showed that CD-modified MNPs are compatible with human whole blood, with no significant impact on platelet activation, hemolysis, or hemostasis.

The antimicrobial and pro-healing properties remain critical clinical objectives for skin wound management. However, the escalating problem of antibiotic overuse and the corresponding rise in bacterial resistance necessitates an urgent shift towards an antibiotic-free approach to antibacterial treatment. The quest for antimicrobial efficacy while accelerating wound healing without antibiotic treatment have emerged as innovative strategies in skin wound treatment. Here, a dual-function hydrogel with antimicrobial and enhanced tissue-healing properties was developed by utilizing cyclodextrin, ferrocene, polyethyleneimine (PEI), and Bletilla striata polysaccharide (BSP), through multiple non-covalent interactions, which can intelligently release BSP by recognizing the wound inflammatory microenvironment through the cyclodextrin-ferrocene unit. Moreover, the porosity (65 % - 85 %), Young's modulus (400 KPa - 140 KPa), and DPPH scavenge rate (18 % - 40 %) of the hydrogel are modulated by varying the BSP content. The hydrogel exhibits outstanding antibacterial properties (98.3 % reduction of Escherichia coli observed after exposure to HTFC@BSP-20 for 24 h) and favorable biocompatibility. Furthermore, in a rat full-thickness skin wound model, the dual-function hydrogel significantly accelerates wound healing, increased CD31 expression promotes vascular regeneration, reduced TNF-α express and inhibited the inflammation. This multifunctional ROS responsive hydrogel provides a new perspective for antibiotics-free treatment of skin injuries., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work. There is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024. Published by Elsevier B.V.)

Synthesis of polyurethane-type poly[3]rotaxanes is achieved by polyaddition between a cyclodextrin (CD)-based [3]rotaxane diol and various diisocyanate species, which provide a more defined structure compared to conventional polyrotaxane syntheses. In this study, hydroxyl groups on CDs of [3]rotaxane diol are initially acetylated, and deprotected after the polyaddition to introduce polyurethane backbone structure into polyrotaxane framework. Despite a relatively complicated chemical structure, [3]rotaxane diol monomer is successfully synthesized in a high yield (overall 67%) without any taxing purification process, which is beneficial for practical applications. The polymerization itself proceeds well under a standard polyaddition reaction condition to afford corresponding polyurethanes around 80% yield with M n > 30 kDa. The poly[3]rotaxanes show different aggregation behavior or optical properties, whether or not acetyl groups are present, and are analyzed by XRD, SEM, and fluorescence measurements., (© 2024 The Author(s). Macromolecular Rapid Communications published by Wiley‐VCH GmbH.)

This work aimed to explore an alternative to the use of antibiotics for prevention and treatment of wounds infection caused by two common bacterial pathogens Staphylococcus aureus and Pseudomonas aeruginosa. For this purpose, three different essential oil components (EOCs), namely carvacrol, citronellol and cinnamic acid, were loaded into electrospun fibers of poly-ε-caprolactone (PCL) aided by alpha-cyclodextrin (αCD) and hydroxypropyl-β-cyclodextrin (HPβCD). Electrospun-fibers prepared with each EOC and their mixtures were screened for antimicrobial capability and characterized regarding morphological, mechanical, thermal, surface polarity, antibiofilm and antioxidant properties. αCD formed poly(pseudo)rotaxanes with PCL and weakly interacted with EOCs, while HPβCD facilitated EOC encapsulation and formation of homogeneous fibers (500-1000 nm diameter) without beads. PCL/HPβCD fibers with high concentration of EOCs (mainly carvacrol and cinnamic acid) showed strong antibiofilm (>3 log CFU reduction) and antioxidant activity (10-50% DPPH scavenging effects). Different performances were recorded for the EOCs and their mixtures; cinnamic acid migrated to fiber surface and was released faster. Fibers biocompatibility was verified using hemolysis tests and in ovo tissue integration and angiogenesis assays. Overall, HPβCD facilitates complete release of EOCs from the fibers to the aqueous medium, being an environment-friendly and cost-effective strategy for the treatment of infected 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 The Authors. Published by Elsevier B.V. All rights reserved.)

The influence of alpha-cyclodextrin (αCD) on PEG crystallization is examined for a peptide-PEG conjugate, YYKLVFF-PEG3k comprising an amyloid peptide YYKLVFF linked to PEG with molar mass 3 kg mol -1 . Remarkably, differential scanning calorimetry (DSC) and simultaneous synchrotron small-angle/wide-angle X-ray scattering (SAXS/WAXS) show that crystallization of PEG is suppressed by αCD, provided that the cyclodextrin content is sufficient. A hexagonal mesophase is formed instead. The αCD threading reduces the conformational flexibility of PEG, and hence suppresses crystallization. These results show that addition of cyclodextrins can be used to tune the crystallization of peptide-polymer conjugates and potentially other polymer/biomolecular hybrids., (© 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

STING agonists are potent enhancers of a pro-inflammatory response and, thus, potentially useful therapeutics. Unfortunately, many agonists developed to date require complex drug delivery formulations and often have poor water solubility, limiting their use for systemic administration. Here, we report the discovery and chemical characterization of lactones of MSA-2 as new STING prodrugs with enhanced properties. We show that these prodrugs form efficient inclusion complexes with tumor myeloid cell targeting cyclodextrin nanoparticles and propose a new mechanism of formation and hydrolysis., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

Aiming to improve the retrieval rate of retrievable vena cava filters (RVCF) and extend its dwelling time in vivo, a novel hydrogel coating loaded with 10 mg/mL heparin and 30 mg/mL cyclodextrin/paclitaxel (PTX) inclusion complex (IC) was prepared. The drug-release behavior in the phosphate buffer solution demonstrated both heparin and PTX could be sustainably released over approximately two weeks. Furthermore, it was shown that the hydrogel-coated RVCF (HRVCF) with 10 mg/mL heparin and 30 mg/mL PTX IC effectively extended the blood clotting time to above the detection limit and inhibited EA.hy926 and CCC-SMC-1 cells' proliferation in vitro compared to the commercially available bare RVCF. Both the HRVCF and the bare RVCF were implanted into the vena cava of sheep and retrieved at at 2nd and 4th week after implantation, revealing that the HRVCF had a significantly higher retrieval rate of 67 % than the bare RVCF (0 %) at 4th week. Comprehensive analyses, including histological, immunohistological, and immunofluorescent assessments of the explanted veins demonstrated the HRVCF exhibited anti-hyperplasia and anticoagulation properties in vivo, attributable to the hydrogel coating, thereby improving the retrieval rate in sheep. Consequently, the as-prepared HRVCF shows promising potential for clinical application to enhance the retrieval rates of RVCFs., 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.)

Purpose: We aimed to prepare a β-cyclodextrin (β-CD) polymer using radical polymerization with co-monomers, 6-deoxy-6-(2-methacryloyloxyethylsuccinamide)-β-cyclodextrin (CD-MSAm) and N,N,N-trimethyl-N-(2-hydroxy-3-metacryloyloxopropyl)-ammonium chloride (QA) to design cyclodextrins suitable for use in ophthalmology. In addition, we evaluated their solubility and inclusion properties with rebamipide (REB), a poorly soluble drug, and investigated the usefulness of the β-CD polymer and REB (REB@CDQA) combination in treating dry eye., Methods: The β-CD polymer (CD-MSAm-co-QA, CDQA) based on CD-MSAm/QA was prepared via radical polymerization, and the usefulness of REB@CDQA in treating dry eye was evaluated using a rabbit treated with N-acetylcysteine (dry eye model)., Results: The solubility of the CDQA powder was higher than that of the β-CD powder, and 80 nm colloids were observed in the CDQA solution. No corneal toxicity was observed in human corneal epithelial cells or rat corneas treated with 0.2% CDQA solution. The levels of REB dissolved in the CDQA solution were higher than those of the β-CD solution. Moreover, the application of the CDQA solution enhanced REB retention in the cornea and attenuated the transcorneal penetration of REB. In addition, instillation of REB@CDQA enhanced the volume of the lacrimal fluid and normalized the reduced mucin levels in the dry eye model. The extent of tear film breakup was attenuated by REB@CDQA instillation., Conclusion: The CDQA solution enhanced the solubility of REB, and the combination of CDQA and REB enhanced the drug content in the corneal tissue. Moreover, the therapeutic effect on dry eye was higher than that of REB suspensions without CDQA., Competing Interests: Ko Kobayashi, Masaru Matsuda, Norio Iwakiri, and Eiji Harata worked for NOF CORPORATION. The authors declare no other conflicts of interest in this work., (© 2024 Otake et al.)

Corneal diseases, a leading cause of global vision impairment, present challenges in treatment due to corneal tissue donor scarcity and transplant rejection. Hydrogel biomaterials in the form of corneal implants for tissue regeneration, while promising, have faced obstacles related to cellular and tissue integration. This study develops and investigates the potential of granular polyrotaxane (GPR) hydrogels as a scaffold for corneal keratocyte growth and transparent tissue generation. Employing host-guest driven supramolecular interactions, we developed injectable, cytocompatible hydrogels. By optimizing cyclodextrin (CD) concentrations in thiol-ene crosslinked PEG microgels, we observed improved mechanical properties and thermoresponsiveness while preserving injectability. These microgels, adaptable for precise defect filling, 3D printing or tissue culture facilitate enhanced cellular integration with corneal keratocytes and exhibit tissue-like structures in culture. Our findings demonstrate the promise of GPR hydrogels as a minimally invasive avenue for corneal tissue regeneration. These results have the potential to address transplantation challenges, enhance clinical outcomes, and restore vision.

Atherosclerosis is a persistent inflammatory condition of the blood vessels associated with abnormalities in lipid metabolism. Development of biomimetic nanoplatforms provides an effective strategy. Herein, inspired by the peptide CLIKKPF spontaneously coupling to phosphatidylserine (PS) on the inner leaflet of cell membranes specifically, MM@NPs were constructed by macrophage membrane spontaneous encapsulation of cyclodextrin-based nanoparticles modified with the peptide CLIKKPF and loaded with the hydrophobic compound resveratrol. MM@NPs could be specifically phagocytized by the activated endothelium with the overexpressed VCAM-1 for enhancing target delivery into the pathological lesion. Additionally, for the ApoE -/- mice, MM@NPs provide comprehensive treatment efficiency in reducing oxidant stress, alleviating the inherent inflammation, and decreasing cholesterol deposition, subsequently resulting in the atherosclerotic plaque regression. Therefore, MM@NPs could be one possible candidate for improving lipid metabolism and inflammation in atherosclerosis.

Cyclodextrin metal-organic framework (CD-MOF) is an edible and porous material that can serve as a template for synthesizing small-sized metal nanoparticles. However, its highly hydrophilic nature has limited its wider application. Herein, ultra-small gold nanoparticles (U-AuNPs) were loaded into CD-MOF to produce a composite material Au@CD-MOF. The CD-MOF was utilized as a template to control the size of the AuNPs. The synthesized Au@CD-MOF was easily dispersible in aqueous medium and its released U-AuNPs exhibited effective water dispersion stability within 120 days. Additionally, compared to gold nanoparticles prepared using traditional methods (T-AuNPs), the U-AuNPs exhibited superior antibacterial properties. Furthermore, hydrophilic Au@CD-MOF was incorporated into a hydrophobic polydimethylsiloxane (PDMS) matrix (Au@CD-MOF/PDMS) to achieve a humidity-responsive antibacterial function. The composite membrane exhibited remarkable responsiveness to humidity, showing almost no release of U-AuNPs at 0 % humidity. However, it exhibited approximately 89 % release within 1 h, and complete release of U-AuNPs was observed within 4 h under 100 % humidity. These findings highlight the successful preparation of a humidity-responsive antibacterial composite membrane, which has great potential applications in various scenarios, particularly in the field of antibacterial food packaging., 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.)

Ophthalmic tacrolimus compounded formulations are usually made from the commercial intravenous presentation, which contains ethanol as a solubilizer due to the low solubility of tacrolimus. The use of cyclodextrins is presented as an alternative to ethanol, an ocular irritant excipient, to avoid its long-term irritant effects. Open-label, sequential, prospective study to compare effectiveness, safety, and adherence of a new formulation of 0.015% tacrolimus with cyclodextrins (TCD) versus 0.03% tacrolimus with ethanol (TE). The ocular evaluation was assessed by ocular signs, corneal staining, subjective questionnaires as Visual Function Questionnaire (VFQ-25) and Visual Analogue Scale (VAS) of symptoms, lacrimal stability, ocular redness, and intraocular pressure. Compliance was assessed by VAS of adherence and empirically (difference between theoretical and actual consumption). Clinical ocular signs and corneal staining score remained stable for most patients 3 months after switching formulations. The TCD formulation did not modify the tear stability and intraocular pressure of the treated patients compared to the TE formulation. TCD eye drops significantly decreased the subjective pain values on VFQ-25 scale and burning sensation on the VAS symptom scale in comparison to TE formulation after 3 months after the change to TCD formulation. The novel tacrolimus in cyclodextrins formulation is a promising alternative for treating inflammatory ocular pathologies refractory to first-line treatments.

KLEPTOSE ® CRYSMEB methylated cyclodextrin derivative displays less methylated group substitution than randomly methylated cyclodextrin. It has demonstrated an impact on atherosclerosis and neurological diseases, linked in part to cholesterol complexation and immune response, however, its impact on inflammatory cascade pathways is not clear. Thus, the impact of KLEPTOSE ® CRYSMEB on various pharmacological targets was assessed using human umbilical vein endothelial cells under physiological and inflammatory conditions, followed by screening against twelve human primary cell-based systems designed to model complex human tissue and disease biology of the vasculature, skin, lung, and inflammatory tissues using the BioMAP ® Diversity PLUS ® panel. Finally, its anti-inflammatory mechanism was investigated on peripheral blood mononuclear cells to evaluate anti-inflammatory or pro-resolving properties. The results showed that KLEPTOSE ® CRYSMEB can modulate the immune system in vitro and potentially manage vascular issues by stimulating the expression of molecules involved in the crosstalk between immune cells and other cell types. It showed anti-inflammatory effects that were driven by the inhibition of pro-inflammatory cytokine secretion and could have different impacts on different tissue types. Moreover, this cyclodextrin showed no clear impact on pro-resolving lipid mediators. Additionally, it appeared that the mechanism of action of KLEPTOSE ® CRYSMEB seems to not be shared by other well-known anti-inflammatory molecules. Finally, KLEPTOSE ® CRYSMEB may have an anti-inflammatory impact, which could be due to its effect on receptors such as TLR or direct complexation with LPS or PGE2, and conversely, this methylated cyclodextrin could stimulate a pro-inflammatory response involving lipid mediators and on proteins involved in communication with immune cells, probably via interaction with membrane cholesterol.

Currently, Non-Hodgkin Lymphoma (NHL) constitutes 85-90 % of all lymphomas. Clinical treatment of NHL is based on the "4-drug regimen" known as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). Rituximab (RTX) is added to increase the effectiveness and selectivity of the treatment and is the first-line standard treatment for NHL patients. However, success is often prevented by the development of drug resistance. In this study, it was aimed to overcome drug resistance by using two novel tumor-targeted derivatives: guanidine-amphiphilic cyclodextrin (ACD) and guanidine-cyclodextrin polymer (PCD) nanoparticles (NP). These constructs display promise in overcoming drug resistance and enhancing the effectiveness of R-CHOP treatment while potentially eliminating the need for corticosteroid. NP were found to be smaller than 200 nm by dynamic light scattering (DLS). Hemolytic activity and cytotoxicity data on L929 cells demonstrated the safety of the newly synthesized CD derivatives. Additional in vitro characterization studies, including surface charge, physical stability, drug loading capacity, drug release profile, and imaging, as well as conventional and 3D cell culture studies were carried out. Compared to drug solutions, the viability of Daudi human lymphoma cells was statistically significantly decreased in both drug-loaded ACD and PCD NP formulations (p < 0.05). Additionally, RTX-conjugated and drug-loaded ACD NPs exhibited the lowest cell viability due to RTX dependent cytotoxicity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Erem Bilensoy reports financial support was provided by Scientific and Technological Research Council of Turkey. 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.)

Cyclodextrins (CDs) are unique cyclic compounds that can form inclusion complexes via host-guest complexation with a wide range of molecules, thereby altering their physicochemical properties. These molecules offer the formation of inclusion complexes without the formation of covalent bonds, making them suitable for a variety of applications in pharmaceutical and biomedical fields. Due to their supramolecular host-guest properties, CDs are being utilized in the fabrication of biomaterials, metal-organic frameworks, and nano-drug carriers. Additionally, CDs in combination with biomolecules are biocompatible and can deliver nano to macromolecules at the site of drug actions. However, the availability of free hydroxyl groups and a simple crosslinking process for supramolecular fabrication show immense opportunities for researchers in the field of tissue engineering and biomedical applications. In this review article, we have covered the historical development, various types of chemical frameworks, unique chemical and physical properties, and important applications of CDs in drug delivery and biomedical sciences., 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.)

Most chemotherapeutic agents are poorly soluble in water, have low selectivity, and cannot reach the tumor in the desired therapeutic concentration. On the other hand, sensitive hydrophilic therapeutics like nucleic acids and proteins suffer from poor bioavailability and cell internalization. To solve this problem, new types of controlled release systems based on nano-sized self-assemblies of cyclodextrins able to control the speed, timing, and location of therapeutic release are being developed. Cyclodextrins are macrocyclic oligosaccharides characterized by a high synthetic plasticity and potential for derivatization. Introduction of new hydrophobic and/or hydrophilic domains and/or formation of nano-assemblies with therapeutic load extends the use of CDs beyond the tried-and-tested CD-drug host-guest inclusion complexes. The recent advances in nano drug delivery have indicated the benefits of the hybrid amphiphilic CD nanosystems over individual CD and polymer components. This review provides a comprehensive overview of the most recent advances in the design of CDs self-assemblies and their use for delivery of a wide range of therapeutic molecules. It aims to offer a valuable insight into the many roles of CDs within this class of drug nanocarriers as well as current challenges and future perspectives.

Cyclodextrins are ring-shaped sugars used as additives in medications to improve solubility, stability, and sensory characteristics. Despite being widespread, Chagas disease is neglected because of the limitations of available medications. This study aims to review the compounds used in the formation of inclusion complexes for the treatment of Chagas disease, analyzing the incorporated compounds and advancements in related studies. The databases consulted include Scielo, Scopus, ScienceDirect, PubMed, LILACS, and Embase. The keywords used were "cyclodextrin AND Chagas AND disease" and "cyclodextrin complex against Trypanosoma cruzi ". Additionally, a statistical analysis of studies on Chagas disease over the last five years was conducted, highlighting the importance of research in this area. This review focused on articles that emphasize how cyclodextrins can improve the bioavailability, therapeutic action, toxicity, and solubility of medications. Initially, 380 articles were identified with the keyword "cyclodextrin AND Chagas disease"; 356 were excluded for not being directly related to the topic, using the keyword "cyclodextrin complex against Trypanosoma cruzi ". Over the last five years, a total of 13,075 studies on Chagas disease treatment were found in our literature analysis. The studies also showed interest in molecules derived from natural products and vegetable oils. Research on cyclodextrins, particularly in the context of Chagas disease treatment, has advanced significantly, with studies highlighting the efficacy of molecules in cyclodextrin complexes and indicating promising advances in disease treatment.

Glucocorticoids are widely used for treating allergic rhinitis, but conventional intranasal administration encounters unfavorable nasal cilia clearance and nasal mucosal barrier. Herein, a bilateral microneedle patch is fabricated for delivering cyclodextrin-based metal-organic frameworks (CD-MOF) encapsulating dexamethasone (DXMS) and paeonol (Pae), while NaH particles are mounted on the basal part of each microneedle. By intranasal administration, the microneedles are propelled into the nasal mucosa by NaH-generated hydrogen and then swell to form a hydrogel for sustainedly releasing drugs. The DXMS/Pae combination is demonstrated to be superior to more than the twofold dose of DXMS alone for improving allergic rhinitis in rats. It involves reducing mast cell degranulation and modulating Treg/Th17 cell homeostasis, whereas inhibiting Th1 to Th2 differentiation is associated with regulating the GATA3/T-bet pathway, as well as repairing epithelial barrier function by increasing MUC1 and downregulating periostin. In addition, this delivery system modulates the lipid metabolism of the nasal mucosa. Notably, the newly designed device significantly enhances the drug's therapeutic effect, and NaH-generated hydrogen may have the potential adjunctive therapeutic effect. Collectively, such an emerging microneedle-mediated nasal drug delivery creates a new form for alleviating immune inflammation and contributes a promising solution to reduce clinical glucocorticoid abuse., (© 2024 Wiley‐VCH GmbH.)

Owing to their incomplete digestion in the human body and inadequate removal by sewage treatment plants, antiepileptic drugs (AEDs) accumulate in water bodies, potentially affecting the exposed humans and aquatic organisms. Therefore, sensitive and reliable detection methods must be urgently developed for monitoring trace AEDs in environmental water samples. Herein, a novel phenylboronic acid-functionalized magnetic cyclodextrin microporous organic network (Fe 3 O 4 @CD-MON-PBA) was designed and synthesized via the thiol-yne click post-modification strategy for selective and efficient magnetic solid-phase extraction (MSPE) of trace AEDs from complex sample matrices through the specific B-N coordination, π-π, hydrogen bonding, electrostatic, and host-guest interactions. Fe 3 O 4 @CD-MON-PBA exhibited a large surface area (118.5 m 2  g -1 ), rapid magnetic responsiveness (38.6 emu g -1 , 15 s), good stability and reusability (at least 8 times), and abundant binding sites for AEDs. Under optimal extraction conditions, the proposed Fe 3 O 4 @CD-MON-PBA-MSPE-HPLC-UV method exhibited a wide linear range (0.5-1000 μg L -1 ), low limits of detection (0.1-0.5 μg L -1 ) and quantitation (0.3-2 μg L -1 ), good anti-interference ability, and large enrichment factors (92.2-104.3 to 92.3-98.0) for four typical AEDs. This work confirmed the feasibility of the thiol-yne click post-synthesis strategy for constructing novel and efficient multifunctional magnetic CD-MONs for sample pretreatment and elucidated the significance of B-N coordination between PBA and N-containing AEDs., 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.)

Background: Vitamin E ( -tocopherol) and cholesterol are crucial components in cellular protection and physiological processes. Their uses in biological media face challenges due to their poor solubility and stability., Objective: The study investigated the complex interactions of these bioactive compounds in various encapsulation systems of cyclodextrin and liposome, as well as dispersion in PEG-6000, in an attempt to improve the viability, motility, and preservation of ovine sperm cells., Materials and Methods: The work explored the in vitro dissolution kinetics of vitamin E (d-tocopherol) and cholesterol using semi-empirical models., Results: The release profiles of VitE and Chl varied considerably, depending on the specific carrier systems. For liposome-loaded VitE and Chl, the Korsmeyer-Peppas model gave the best fit; for CD/VitE and CD/Chl, the Higuchi model provided the best fit, whereas for PEG-6000 dispersions (VitE and Chl) both the Higuchi and Korsmeyer-Peppas models demonstrated the excellent fit. All systems indicated a Fickian diffusion mechanism dictated by the concentration gradient. The delivery of VitE and Chl with CD, liposome and PEG dispersion significantly increased sperm mobility and motility. The effect on the VCL parameter was the greatest by liposome-loaded VitE and Chl, followed by CD encapsulation and PEG-6000 dispersion., Conclusion: The dynamics of vitamin E and cholesterol within innovative delivery systems offers valuable insights into the development of advanced solutions in reproductive health, particularly on improving the viability, motility of refrigerated ovine sperm cells. Doi.org/10.54680/fr24510110712.

The current pharmacological management of androgenetic alopecia is inconvenient and requires a discipline that patients find difficult to follow. This reduces compliance with treatment and satisfaction with results. It is important to propose treatment regimens that increase patient compliance and reduce adverse effects. This work describes transdermal delivery of minoxidil partially encapsulated in β-cyclodextrin and assisted by photoacoustic waves. Photoacoustic waves transiently increase the permeability of the skin and allow for the delivery of encapsulated minoxidil. A minoxidil gel formulation was developed and the transdermal delivery was studied in vitro in the presence and absence of photoacoustic waves. A 5-min stimulus with photoacoustic waves generated by light-to-pressure transducers increases minoxidil transdermal delivery flux by approximately 3-fold. The flux of a 1% minoxidil formulation promoted by photoacoustic waves is similar to the passive flux of a 2% minoxidil commercial formulation. Release of minoxidil from β-cyclodextrin increases dermal exposure without increasing peak systemic exposure. This promotes hair growth with fewer treatments and reduced adverse effects. In vivo studies using encapsulated minoxidil and photoacoustic waves yielded 86% hair coat recovery (vs. 29% in the control group) and no changes in the blood pressure., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LGA and CS are shareholders of LaserLeap Technologies, which provided the materials employed to generate the photoacoustic waves used in this work., (Copyright © 2024. Published by Elsevier B.V.)

The design of hydrophilic polyvinylidene fluoride (PVDF) membranes with anti-fouling properties has been explored for decades. Surface modification and blending are typical strategies to tailor the hydrophilicity of PVDF membranes. Herein, cyclodextrin was used to improve the antifouling performance of PVDF membranes. Cyclodextrin-modified PVDF membranes were prepared by coupling PVDF amination (blending with branched polyethyleneimine) and activated cyclodextrin grafting. The blending of PEI in the PVDF casting solution preliminarily aminated the PVDF, resulting in PEI-crosslinked/grafted PVDF membranes after phase inversion. Aldehydes groups on cyclodextrin, introduced by oxidation, endow cyclodextrin to be grafted on the aminated PVDF membrane by the formation of imines. Borch reduction performed on the activated cyclodextrin-grafted PVDF membrane converted the imine bonds to secondary amines, ensuring the membrane stability. The resulting membranes possess excellent antifouling performance, with a lower protein adsorption capacity (5.7 μg/cm 2 , indicated by Bovine Serum Albumin (BSA)), and a higher water flux recovery rate (FRR = 96%). The proposed method provides a facial strategy to prepare anti-fouling PVDF membranes., 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.)

Hydrogel-forming microneedle array patches (HFMAPs) are microneedles that create microconduits upon insertion and swelling in the skin, potentially allowing prolonged drug delivery without generating sharps waste. Delivering hydrophobic drugs using HFMAPs poses challenges, which can be addressed using solubility enhancers such as cyclodextrins (CDs). This study aimed to deliver risperidone (RIS) transdermally using HFMAPs. To enhance the aqueous solubility of RIS hydroxypropyl-beta-cyclodextrin (HP-β-CD) and hydroxypropyl-gamma-cyclodextrin (HP-γ-CD) were utilised and their performance was tested using phase solubility studies. The aqueous solubility of RIS was enhanced by 4.75-fold and 2-fold using HP-β-CD and HP-γ-CD, respectively. RIS-HP-β-CD complex (CX) and physical mixture (PM) directly compressed tablets were prepared and combined with HFMAPs. Among the tested formulations, RIS-HP-β-CD PM reservoirs with 11 x 11 PVA/PVP HFMAPs exhibited the best performance in ex vivo studies and were further evaluated in in vivo experiments using female Sprague Dawley rats. The extended wear time of the MAPs resulted in the sustained release of RIS and its active metabolite 9-hydroxyrisperidone (9-OH-RIS) in plasma samples, lasting from 3 to 5 days with a 1-day application and up to 10 days with a 5-day application. For a 1-day application, HFMAPs showed greater systemic exposure to RIS compared to intramuscular control (AUC 0-t : 13330.05 ± 2759.95 ng/mL/hour versus 2706 ± 1472 ng/mL/hour). Moreover, RIS exposure was extended to 5 days (AUC 0-t : 12292.37 ± 1801.94 ng/mL/hour). In conclusion, HFMAPs could serve as an alternative for delivering RIS in a sustained manner, potentially improving the treatment of schizophrenia., 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 B.V. All rights reserved.)

The purpose of this study involved the synthesis of supramolecular reservoir (i.e. cyclodextrin metal-organic framework, MOF) using cyclodextrins as building blocks, followed by cross-linking to obtain crosslinked CD framework (CDF) using CD-MOF as template and functionalized with borneol (BO) to enhance rivastigmine (RIV) permeation and facilitate brain targeting via intranasal administration. Utilizing BO modified CDF (BO-CDF) with cubic shape as a carrier for the encapsulation of RIV, a nasal RIV delivery system (RIV@BO-CDF) was fabricated. The particle size of RIV@BO-CDF was approximately 250 nm, and the drug loading capacity reached 15 ± 2 %. BO-CDF improved the mucoadhesion and enhanced RIV permeability with the plasma concentration-time curve (AUC), the brain AUC and the peak drug concentration within brain in rats 1.7, 2.3 and 8 times than that of oral RIV solution, respectively. The relative drug targeting efficiency percentage (DTE, 139.4 %) and direct drug transfer percentage (DTP, 28.3 %) of RIV@BO-COF indicated good targeting efficiency and direct nose-to-brain drug delivery. Overall, this study provides a potential application of supramolecular cyclodextrin-based reservoir to enhance the brain targeting and efficacy of the RIV via nasal delivery., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Weifeng Zhu reports financial support was provided by the financial support from Central Guidance for Local Scientific and Technological Development Funding Projects. 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 Ltd. All rights reserved.)

Drug loading capacity is a crucial character of nano-scaled drug carriers to achieve high quality pharmaceutical preparations. However, efficient encapsulation of water-soluble small molecular drugs still faces large obstacles in many cases. Herein, we designed a novel supramolecular delivery system constructed by poly(β-cyclodextrin) containing benzoic acid groups (PCD-PA) and adamantyl terminated poly(ethylene glycol) (PEG-AD) to provide multiple intermolecular interactions for competent loading of water-soluble small-molecular drugs. PCD-PA had multiple host molecules, and PEG-AD could be inserted via host-guest interaction in different proportion to adjust the composition of supramolecular carrier. Meanwhile, π-π stacking and electrostatic interaction furnished by benzoic acid groups served as binding force for drug entrapment, which led to considerable loading capacity for several water-soluble drugs. Among the drugs with different chemical structures, mitoxantrone hydrochloride and doxorubicin hydrochloride bearing anthraquinone rings and several protonable amino groups acquired the highest loading content as about 14 % in PCD-PA3/PEG-AD supramolecular self-assemblies. Further computational simulations investigated the mechanism of drug loading based on the interactions between the carrier materials and the payloads. In addition, the weakly acidic environment obviously accelerated the release of certain drugs. All in all, this self-assembled supramolecular nano-system displayed great potentials as a delivery platform for diverse water-soluble drugs., 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.)

Chronic kidney disease entails a progressive decline in kidney function, hindering the kidneys' ability to excrete fluid, electrolytes, and metabolites. This dysfunction leads to metabolite accumulation in the bloodstream, which can reach toxic concentrations. Hemodialysis is an effective means of treating patients with kidney failure, but it does not clear all toxins effectively. Engineered nano-adsorbents can potentially improve the removal of retained toxins, particularly protein-bound types. Magnetic nanoparticles coated with α-, β-, and γ-cyclodextrin were synthesized, and physicochemical properties were characterized using thermogravimetric analysis, transmission electron microscopy, dynamic light scattering, and ζ-potential for their physiochemical properties. The effect of surface chemistry and incubation time on toxin adsorption was investigated using quantitative mass spectrometry techniques. All particle types demonstrated toxin adsorption to some level. Overall, the adsorption process was independent of metabolite concentration, suggesting a dynamic interplay between surface properties and solution composition. This insight will contribute to developing innovative adsorbent films designed to remove uremic toxins effectively., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Larry Unsworth reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. Larry Unsworth reports financial support was provided by Alberta Innovates. 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tolperisone is a centrally acting muscle relaxant that has been used for the treatment of post-stroke spasticity and low back pain. Recently, the safety of tolperisone pharmaceutical products has been reassessed due to growing concerns over allergic adverse events. Reactive degradants of tolperisone may be responsible for these hypersensitivity reactions. By forming adducts with proteins, they may act as haptens that could evoke allergic reactions. The objective of this study was to examine the presence of these degradants in tolperisone pharmaceutical products and to assess their reactivity to elucidate their possible role in the pro-allergic effect of tolperisone. For this purpose, capillary electrophoresis UV detection (CE-UV) method was developed and validated for the quantification of degradants. A dual cyclodextrin system was applied to achieve the appropriate migration order enabling the analysis of 2-methyl-1-(4-methylphenyl)prop-2-en-1-one (MMP) and 1-(4-methylphenyl)propan-1-one (MMPO) in the presence of high concentrations of tolperisone. MMP was identified as the main degradant in forced degradation tests of the active pharmaceutical ingredient. Differences in MMP content of tolperisone products by different manufacturers have also been found, highlighting the role of formulation in their stability. High reactivity of MMP was demonstrated as rapid and almost complete adduct formation with cysteine was found. This degradant thus might be responsible for the allergic adverse effects of tolperisone even when it is present in trace amounts in tablets by readily reacting with proteins in vivo., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter P. Lakatos reports financial support was provided by Hungarian Ministry for Culture and Innovation, Hungary. The authors (P.P.L., T.T. and É.Sz.) have previously worked with MEDITOP Pharmaceuticals Ltd. on another project supported by the “Competitiveness and excellence cooperations” project (2018-1.3.1-VKE-2018-00030) provided by the National Research, Development, and Innovation Fund of Hungary, Hungary. The authors’ task was to study the pharmacodynamic properties of tolperisone. 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Transmembrane nanopores, as key elements in molecular transport and single-molecule sensors, are assembled naturally from multiple monomers in the presence of lipid bilayers. The nanopore size, especially the precise diameter of the inner space, determines its sensing targets and further biological application. In this paper, we introduce a template molecule-aided assembly strategy for constructing size-tunable transmembrane nanopores. Inspired by the barrel-like structure, similar to many transmembrane proteins, cyclodextrin molecules of different sizes are utilized as templates and modulators to assemble the α-helical barreled peptide of polysaccharide transporters (Wza). The functional nanopores assembled by this strategy possess high biological and chemical activity and can be inserted into lipid bilayers, forming stable single channels for single-molecule sensing. After enzyme digestion, the cyclodextrins on protein nanopores can be degraded, and the remaining nontemplate transmembrane protein nanopores can also preserve the integrity of their structure and function. The template molecule-aided assembly strategy employed a simple and convenient method for fully artificially synthesizing transmembrane protein nanopores; the pore size is completely dependent on the size of the template molecule and controllable, ranging from 1.1 to 1.8 nm. Furthermore, by chemically synthesized peptides and modifications, the pore function is easily modulated and does not involve the cumbersome genetic mutations of other biological techniques., 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.)

Development of novel active pharmaceutical ingredients (API) for oral use often face challenges due to low bioavailability. Nanoparticle-based drug delivery systems and cyclodextrin (CD) encapsulation offer promising solutions by enhancing API solubility or dissolution rates. Porous silicon nanoparticles have shown potential to encapsulate APIs in their amorphous form within the pores, improving their dissolution rates compared to crystalline counterparts. A novel synthesis approach, circumventing the expensive and tedious synthesis from Si wafer material, has been developed using centrifugal Chemical Vapor Deposition (cCVD). Herein, various cCVD Si particles were evaluated for their ability to enhance the dissolution rate of the model drugs celecoxib (CEL), phenytoin (PHT), griseofulvin (GRI), diclofenac (DCF) and naproxen (NAP). Our findings demonstrate increased dissolution rates of all tested APIs when formulated with cCVD Si particles, compared to free API in pH 7.4 or pH 2.0. Particle characteristics were largely retained after loading, and the solid state of the loaded APIs were evaluated using Differential Scanning Calorimetry (DSC). Dissolution kinetics were influenced by the particle properties, mass loading and API characteristics. Loading of CD-CEL, -GRI and -DCF complexes into the cCVD Si particles showed a potential for further enhanced dissolution rates, representing the first reported investigation of this combination. In conclusion, the cCVD Si particles are promising for improving the dissolution rate of poorly soluble drugs, potentially due to precipitation of amorphous or metastable forms. Further enhancements were observed upon loading CD-drug complexes, thereby offering promising strategies for optimizing drug bioavailability., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jo Klaveness, Werner Filtvedt and Hennie Marie Johnsen are inventors of a patent application with the title “Silicon particles for drug delivery”. The assignee of the patent application is Nacamed AS. Werner Filtvedt and Jo Klaveness have shares in Nacamed AS. Marianne Hiorth is an editor for the “Journal of Drug Delivery Science and Technology”., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Nanoparticles (NPs) have gained significant attention in recent years due to their potential applications in pharmaceutical formulations, drug delivery systems, and various biomedical fields. The versatility of colloidal NPs, including their ability to be tailored with various components and synthesis methods, enables drug delivery systems to achieve controlled release patterns, improved solubility, and increased bioavailability. The review discusses various types of NPs, such as nanocrystals, lipid-based NPs, and inorganic NPs (i.e., gold, silver, magnetic NPs), each offering unique advantages for drug delivery. Despite the promising potential of NPs, challenges such as physical instability and the need for surface stabilization remain. Strategies to overcome these challenges include the use of surfactants, polymers, and cyclodextrins (CDs). This review highlights the role of CDs in stabilizing colloidal NPs and enhancing drug solubility. The combination of CDs with NPs presents a synergistic approach that enhances drug delivery and broadens the range of biomedical applications. Additionally, the potential of CDs to enhance the stability and therapeutic efficacy of colloidal NPs, making them promising candidates for advanced drug delivery systems, is comprehensively reviewed., 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 this study, the association constants of sixteen pesticides with the chiral selector octakis(6-O-tert-butyldimethylsilyl-2,3-di-O-acetyl)-γ-cyclodextrin were determined. The procedure only involved a few experimental measurements; namely, gas hold-up time and retention time of pesticides in capillary columns, as well as column phase ratio at each temperature condition. Fundamental equations of gas-liquid chromatography were used to estimate association constants. Two sets of columns containing different concentrations of the mentioned chiral selector dissolved in (14 %-cyanopropyl-phenyl)-86 %-methyl-polysiloxane were used. One set included capillary columns without any chemical treatment and the other group included columns that were crosslinked. The systematic comparison between both groups indicated a deleterious effect of the crosslinking on enantioselectivity. Our main objective is to promote the use of gas chromatography for the analysis of volatile and semi-volatile chiral pesticides. Thus, we proposed a simple methodology, based only on chromatographic measurements, to obtain information about the enantiorecognition ability of a particular chiral selector constituting the stationary phase and the influence of the selected polymer on the selectivity experimentally obtained., 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.)