γ-Cyclodextrin hydrogel for the sustained release of josamycin for potential ocular application.

Glaucoma is the leading cause of blindness worldwide. However, its surgical treatment, in particular via trabeculectomy, can be complicated by fibrosis. In current clinical practice, application of the drug, Mitomycin C, prevents or delays fibrosis, but can lead to additional side effects, such as bleb leakage and hypotony. Previous in silico drug screening and in vitro testing has identified the known antibiotic, josamycin, as a possible alternative antifibrotic medication with potentially fewer side effects. However, a suitable ocular delivery mechanism for the hydrophobic drug to the surgical site does not yet exist. Therefore, the focus of this paper is the development of an implantable drug delivery system for sustained delivery of josamycin after glaucoma surgery based on crosslinked γ-cyclodextrin. γ-Cyclodextrin is a commonly used solubilizer which was shown to complex with josamycin, drastically increasing the drug's solubility in aqueous solutions. A simple γ-cyclodextrin crosslinking method produced biocompatible hydrogels well-suited for implantation. The crosslinked γ - cyclodextrin retained the ability to form complexes with josamycin, resulting in a 4-fold higher drug loading efficiency when compared to linear dextran hydrogels, and prolonged drug release over 4 days.

Determination of Acetylamantadine by γ-Cyclodextrin-Assisted α-HL Nanopore for Potential Cancer Prediagnosis.

The high expression of Spermidine/spermine N1-acetyltransferase (SSAT-1) is an important indicator in early cancer diagnosis. Here, we developed a nanopore-based methodology with γ-cyclodextrin as an adaptor to detect and quantify acetylamantadine, the specific SSAT-1-catalyzed product from amantadine, to accordingly reflect the activity of SSAT-1. We employ γ-cyclodextrin and report that amantadine cannot cause any secondary signals in γ-cyclodextrin-assisted α-HL nanopore, while its acetylation product, acetylamantadine, does. This allows γ-cyclodextrin to practically detect acetylamantadine in the interference of excessive amantadine, superior to the previously reported ß-cyclodextrin. The quantification of acetylamantadine was not interfered with even a 50-fold amantadine and displayed no interference in artificial urine sample analysis, which indicates the good feasibility of this nanopore-based methodology in painless cancer prediagnosis. In addition, the discrimination mechanism is also explored by 2-D nuclear magnetic resonance (NMR) and nanopore experiments with a series of adamantane derivatives with different hydrophilic and hydrophobic groups. We found that both the hydrophobic region matching effect and hydrophilic interactions play a synergistic effect in forming a host-guest complex to further generate the characteristic signals, which may provide insights for the subsequent design and study of drug-cyclodextrin complexes.

Direct electrospinning for producing multiple activity nanofibers consisting of aggregated luteolin/hydroxypropyl-gamma-cyclodextrin inclusion complex.

Hydroxypropyl-gamma-cyclodextrin (HPγCD) inclusion complex nanofibers (Lut/HPγCD-IC-NF) containing Luteolin (Lut) were prepared by electrospinning technology. Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) spectra confirmed the formation of Lut/HPγCD-IC-NF. Scanning electron microscopy (SEM) images showed that the morphology of Lut/HPγCD-IC-NF was uniform and bead-free, suggesting that self-assembled aggregates, macromolecules with higher molecular weights, were formed by strong hydrogen bonding interactions between the cyclodextrin inclusion complexes. Confocal laser scanning microscopy (CLSM) images showed that Lut was distributed in Lut/HPγCD-IC-NF. Proton nuclear magnetic resonance (1H NMR) spectroscopy revealed the change in chemical shift of the proton peak between Lut and HPγCD, confirming the formation of inclusion complex. Thermogravimetric analysis (TGA) proved that Lut/HPγCD-IC-NF had good thermal stability. The phase solubility test confirmed that HPγCD had a solubilizing effect on Lut. When the solubility of HPγCD reached 10 mM, the solubility of Lut increased by 15-fold. The drug loading test showed that the content of Lut in fibers reached 8.57 ± 0.02 %. The rapid dissolution experiment showed that Lut/HPγCD-IC-NF dissolved within 3 s. The molecular simulation provides three-dimensional evidence for the formation of inclusion complexes between Lut and HPγCD. Antibacterial experiments showed that Lut/HPγCD-IC-NF had enhanced antibacterial activity against S. aureus. Lut/HPγCD-IC-NF exhibited excellent antioxidant properties with a free radical scavenging ability of 89.5 ± 1.1 %. In vitro release experiments showed Lut/HPγCD-IC-NF had a higher release amount of Lut. In conclusion, Lut/HPγCD-IC-NF improved the physicochemical properties and bioavailability of Lut, providing potential applications of Lut in the pharmaceutical field.

Oral Synergism of Egg-White-Derived Peptides (EWDP) and Curcumin for Colitis Mitigation via Polysaccharide/Cyclodextrin Metal-Organic Framework-Based Assemblies.

Recently, oral deliverable strategies of multiple nutraceuticals for ulcerative colitis (UC) mitigation have attracted increasing attention. This study aimed to fabricate facile oral assemblies loaded with egg-white-derived peptides (EWDP) and curcumin based on carboxymethyl chitosan (CMCS) and an γ-cyclodextrin metal-organic framework (MOF). Herein, outer CMCS could coassemble with EWDP (both nutraceuticals and building blocks) into cobweb-like fibrils to promote bridging with inner MOF via coordinative noncovalent interactions (hydrogen bonding, hydrophobic interaction, and electrostatic interaction). Compared with conventional γ-cyclodextrin/MOF-based composites, the above coassembly could also endow the biocompatible assemblies with superior nanoscale colloidal properties, processing applicability (curcumin storage stability, bioaccessibility, and aqueous solubility), and bioactivity. Moreover, the oral synergism of EWDP and curcumin (initially nonsynergistic) for UC mitigation was achieved by alleviating inflammatory damage and gut microbiota imbalance. Overall, the novel assemblies could be a promising amplifier and platform to facilitate oral formulations of various nutraceuticals for food processing and UC relief.

Enhanced Stability and Solidification of Volatile Eugenol by Cyclodextrin-Metal Organic Framework for Nasal Powder Delivery.

Eugenol (Eug) holds potential as a treatment for bacterial rhinosinusitis by nasal powder drug delivery. To stabilization and solidification of volatile Eug, herein, nasal inhalable γ-cyclodextrin metal-organic framework (γ-CD-MOF) was investigated as a carrier by gas-solid adsorption method. The results showed that the particle size of Eug loaded by γ-CD-MOF (Eug@γ-CD-MOF) distributed in the range of 10-150 µm well. In comparison to γ-CD and ß-CD-MOF, γ-CD-MOF has higher thermal stability to Eug. And the intermolecular interactions between Eug and the carriers were verified by characterizations and molecular docking. Based on the bionic human nasal cavity model, Eug@γ-CD-MOF had a high deposition distribution (90.07 ± 1.58%). Compared with free Eug, the retention time Eug@γ-CD-MOF in the nasal cavity was prolonged from 5 min to 60 min. In addition, the cell viability showed that Eug@γ-CD-MOF (Eug content range 3.125-200 µg/mL) was non-cytotoxic. And the encapsulation of γ-CD-MOF could not reduce the bacteriostatic effect of Eug. Therefore, the biocompatible γ-CD-MOF could be a potential and valuable carrier for nasal drug delivery to realize solidification and nasal therapeutic effects of volatile oils.

Covalent modification of γ-cyclodextrin with geraniol: An antibacterial agent with good thermal stability, solubility and biocompatibility.

Geraniol (Ger) is an essential oil molecule with excellent biological activity. High hydrophobicity and volatility limit its practical application. Cyclodextrins (CDs) are water-soluble cyclic oligosaccharides with hydrophobic cavities. Physical encapsulation of CDs to improve the solubility and stability of essential oil molecules is not satisfactory. Therefore, this study synthesized the γ-CD derivative (γ-CD-Ger) by grafting Ger onto γ-CD using a bromide-mediated method. Compared to the inclusion complexes (γ-CD/Ger) formed by both, the derivatives exhibit better solubility and thermal stability. The derivative has better antibacterial activity when the ratio of γ-CD to Ger was 1:2. In addition, the derivatives did not exhibit cytotoxic and hemolytic properties. These results indicate that this research provides a water-soluble antibacterial agent with a wide range of promising applications and offers new ideas for the application of alcohol hydrophobic molecules in aqueous systems.

Effect of cinnamon essential oil/γ-cyclodextrin inclusion complex on papaya quality and shelf-life.

BACKGROUND: Papaya, a highly nutritious and economically significant fruit, is susceptible to infections caused by phytopathogenic fungi. Cinnamon essential oil, derived from Cinnamomum cassia (CC), shows promise in preserving papaya due to its antifungal properties. However, CC is volatile, sensitive to environmental factors, and carries a strong aroma. γ-Cyclodextrin (γ-CD) is known for encapsulating hydrophilic molecules, shielding them from environmental influences, reducing odor, and enabling controlled release due to its unique channel structure. This study aimed to tackle these challenges by preparing and characterizing an inclusion complex of CC with γ-CD (CC-γ-CD), and subsequently evaluating its efficacy in preserving papaya fruits. RESULTS: Analyses, including Fourier-infrared, powder X-ray diffraction, thermal gravity analysis, differential scanning calorimeter, and scanning electron microscopy, revealed successful encapsulation of CC components within the γ-CD cavity. Evaluations of the CC-γ-CD complex's impact on papaya fruit shelf life and quality showed notable enhancements. Fruits treated with CC-γ-CD inclusion complex at a dose of 10 g kg-1 exhibited a 55% extension in shelf-life, evidenced by reduced disease severity index compared with untreated fruit in the same storage conditions. Detailed physicochemical and bromatological assessments highlighted significant improvements, particularly in fruit treated with CC-γ-CD inclusion complex at a dose of 10 g kg-1. CONCLUSION: The application of CC-γ-CD inclusion complex at 10 g kg-1 extended the shelf-life of papaya fruit, significantly and markedly improved the overall quality. These findings underscore the potential of the CC-γ-CD inclusion complex as an effective preservative for papaya, offering a promising solution for its postharvest management and marketability. © 2024 Society of Chemical Industry.

Unraveling the molecular dynamics of sugammadex-rocuronium complexation: A blueprint for cyclodextrin drug design.

Sugammadex, marketed as Bridion™, is an approved cyclodextrin (CD) based drug for the reversal of neuromuscular blockade in adults undergoing surgery. Sugammadex forms an inclusion complex with the neuromuscular blocking agent (NMBA) rocuronium, allowing rapid reversal of muscle paralysis. In silico methods have been developed for studying CD inclusion complexes, aimed at accurately predicting their structural, energetic, dynamic, and kinetic properties, as well as binding constants. Here, a computational study aimed at characterizing the sugammadex-rocuronium system from the perspective of docking calculations, free molecular dynamics (MD) simulations, and biased metadynamics simulations with potential of mean force (PMF) calculations is presented. The aim is to provide detailed information about this system, as well as to use it as a model system for validation of the methods. This method predicts results in line with experimental evidence for both the optimal structure and the quantitative value for the binding constant. Interestingly, there is a less profound preference for the orientation than might be assumed based on electrostatic interactions, suggesting that both orientations may exist in solution. These results show that this technology can efficiently analyze CD inclusion complexes and could be used to facilitate the development and optimization of novel applications for CDs.

γ-Cyclodextrin metal-organic frameworks as the promising carrier for pulmonary delivery of cyclosporine A.

γ-Cyclodextrin metal-organic frameworks (CD-MOFs) are considered as a green and biocompatible material with great potential in drug delivery systems. Original CD-MOFs show the poor aerosol properties, which limit the application in pulmonary drug delivery. To improve the in vitro deposition properties, herein, we synthesized CD-MOFs by the vapor diffusion method using a series of modulators to achieve better pulmonary delivery of cyclosporine A (CsA). The results showed that blank CD-MOFs and drug loaded CD-MOFs prepared with different modulators all preserved the cubical shape, and exhibited the similar crystal form, structural characteristics, thermal behaviors and release properties. In addition, drug loaded CD-MOFs prepared with polyethylene glycol 10000 (PEG 10000) as a modulator exhibited better in vitro aerosol performance than those of synthesized using other modulators, and the in vivo pharmacokinetics data demonstrated that the bioavailability of CsA could be significantly enhanced by inhalation administration of drug loaded CD-MOFs compared with oral administration of Neoral®. The repeated dose inhalation toxicity also confirmed the fine biocompatibility of CD-MOFs as the carrier for pulmonary drug delivery. Therefore, the results demonstrated CD-MOFs as the promising carrier could be used for pulmonary drug delivery.

Structure-Chiral Selectivity Relationships of Various Mandelic Acid Derivatives on Octakis 2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl-gamma-cyclodextrin Containing Gas Chromatographic Stationary.

Frequently, a good chiral separation is the result of long trial and error processes. The three-point interaction mechanisms require the fair geometrical fitting and functional group compatibility of the interacting groups. Structure-chiral selectivity correlations are guidelines that can be established via trough systematic studies using model compounds. The enantiorecognition of the test compounds was studied on an octakis 2,3-Di-O-acetyl-6-O-tert-butyldimethylsilyl-gamma-cyclodextrin (TBDMSDAGCD) chiral selector. In our work, mandelic acid and its variously substituted compounds were used as model compounds to establish adaptable rules for other enantiomeric pairs. The mandelic acid and its modified compounds were altered at both their carboxyl and hydroxyl positions to test the key interaction forces of the chiral recognition processes. Ring- and alkyl-substituted mandelic acid derivatives were also used in our experiments. The chiral selectivity values of 20 test compounds were measured and extrapolated to 100 °C. The hydrogen donor abilities of test compounds improved their chiral selectivities. The inclusion phenomenon also played a role in chiral recognition processes in several cases. Enantiomer elution reversals were observed for different derivatives of hydroxyl groups, providing evidence for the multimodal character of the selector. The results of our research can serve as guidelines to achieve appropriate chiral separation for other enantiomeric pairs.

Ethanol-mediated synthesis of γ-cyclodextrin-based metal-organic framework as edible microcarrier: performance and mechanism.

Here, an ethanol-mediated method was introduced to fabricate γ-cyclodextrin-based metal-organic frameworks (γ-CD-MOFs) as microcarriers for epigallocatechin-3-gallate (EGCG). Through adjusting ethanol gas diffusion temperature and ethanol liquid feed speed, we achieved control of crystallization efficiency and crystals size without extra surfactants. Under the sequential regulatory by ethanol in two phases, the obtained γ-CD-MOFs with cubic shape exhibited excellent crystallinity, high surface area, and uniform size distribution. Through the interplay of hydrogen bonding, hydrophobic interactions and π stacking, EGCG molecules could be stored efficiently within cavities and tunnels of the γ-CD-MOFs with high load capability of 334 mg g-1. More importantly, the incorporation of EGCG within frameworks wouldn't disintegrate the unique body-centered cubic structure of γ-CD-MOFs, in turn, would improve the thermostability and antioxidative activity of EGCG. Significantly, all food-grade materials ensured the γ-CD-MOFs high acceptance and applicability for food and biomedical applications.

Efficient controlled release of cannabinoids loaded in γ-CD-MOFs and DPPC liposomes as novel delivery systems in oral health.

Olivetol (OLV), as a cannabidiol (CBD) analog, was incorporated in γ-cyclodextrin metal-organic frameworks (γ-CD-MOFs) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes as potential analgesic drug delivery systems (DDS) for dental hypersensitivity (DH) treatment. These DDS have been scarcely employed in oral health, being the first time in case of MOFs loaded with cannabinoids. In vitro experiments using bovine teeth were performed to verify if the drug is able to reach the dentin, where it can flow to the pulp tissues and exert its analgesic effect; enamel and dentin regions were analyzed by synchrotron radiation-based FTIR microspectroscopy. Principal component analysis (PCA) was used to process the spectroscopic data as a powerful chemometric tool, and it revealed a similar behavior in both regions. The studied DDS have been characterized by different techniques, and is was demonstrated that DDS is an efficient way to carry the drug through dental tissues without compromising their structure.

Sustainable γ-cyclodextrin frameworks containing ultra-fine silver nanoparticles with enhanced antimicrobial efficacy.

Cyclodextrin metal-organic frameworks (CD-MOF) are a class of biocompatible MOF with a great potential in drug delivery applications. Original CD-MOF crystals are fragile and large (0.2-1 mm), which are less useful in pharmaceutical applications. Cetyltrimethylammonium bromide and long chain poly(ethylene) glycol, used in size modulation to produce nanosized CD-MOF can compromise the biocompatibility, and physiochemical properties of CD-MOF as their complete removal from frameworks is difficult. To avoid the use of above-mentioned modulators, herein, we demonstrate the synthesis of nanosized CD-MOF using triethylamine (TEA) as a modulator to reduce their size to ~254 nm. The MOF characteristics such as crystal and chemical structure remain unaffected and the surface area of CD-MOF synthesised with TEA is measured 1075.5 m2/g, almost 50 % higher than those of synthesised using bulky modulators. The improved CD-MOF architecture utilized for the in-situ synthesis of silver nanoparticles resulted in enhanced antimicrobial efficacy tested against Staphylococcus aureus and Escherichia coli bacteria and Candida albicans fungus. And minimum inhibitory concentration (MIC) is recorded in the range of 31-15 µg/mL. Overall, the structural improvement in CD-MOF supported with thorough comparative investigations and enhanced antimicrobial efficacy could be very helpful in further establishing them in biomedicine field.

Recognition of d-Glucose in Water with Excellent Sensitivity, Selectivity, and Chiral Selectivity Using γ-Cyclodextrin and Fluorescent Boronic Acid Inclusion Complexes Having a Pseudo-diboronic Acid Moiety.

Fluorescence recognition of d-glucose in water with excellent sensitivity, selectivity, and chiral selectivity is desired because d-glucose is an essential component in biological and pathological processes. We report an innovative approach that exploits the 1:2 stoichiometric inclusion complexes of γ-cyclodextrin (γ-CyD) with two molecules of fluorescent monoboronic acid-based receptors, which form a pseudo-diboronic acid moiety as the recognition site for d-glucose in water. Two monoboronic acids (1F and 2N) were easily synthesized without heating or column purification. The 1:2 stoichiometric inclusion complexes (1F/γ-CyD and 2N/γ-CyD) were prepared in a mixture of dimethyl sulfoxide/water (2/98 in v/v) by mixing γ-CyD and the corresponding monoboronic acids. Both 1F/γ-CyD and 2N/γ-CyD exhibited strong turn-on response to d-glucose with excellent selectivity over nine other saccharides in the water-rich solvent at pH 7.4 owing to the ditopic recognition of d-glucose by the pseudo-diboronic acid moieties. The limits of detection of 1F/γ-CyD and 2N/γ-CyD for d-glucose were 1.1 and 1.8 µM, respectively, indicating the remarkable sensitivity for the detection of d-glucose at µM levels. 1F/γ-CyD and 2N/γ-CyD also demonstrated chiral-selective recognition of d-glucose, which is apparent from the 2.0- and 6.3-fold enhancement of fluorescence by the addition of d-glucose relative to l-glucose addition, owing to the chiral pseudo-diboronic acid moieties produced by the chiral γ-CyD cavity. To the best of our knowledge, 2N/γ-CyD has the highest d/l selectivity among hitherto reported fluorescent diboronic acid-based receptors.

Rapid detection of rocuronium based on host/guest complex between a pyrene derivative and sugammadex.

Rocuronium is widely used in surgery as a neuromuscular relaxant, but it has been difficult to accurately control its specific dosage in clinical operation. Therefore, the development of fast and instant rocuronium detection methods has important application value for reducing risks and safeguarding health. In this study, N, N, N-trimethyl-4-(pyrene-1-butyl)-ammonium bromide (PyBTA) was designed as a probe to detect rocuronium rapidly. The method relied on replacing PyBTA in sugammadex with rocuronium to induce changes in fluorescence intensity of PyBTA, thereby realizing quantitative detection. Its sensing performance and detection mechanism were explored systematically by spectroscopy. The linear range of this method was 0.5-10 µM and the detection limit of it was 0.3 µM. In addition, we confirmed that the host-guest interaction among PyBTA, sugammadex, and rocuronium was mainly driven by electrostatic and hydrophobic interactions.

Stabilization of Octahedral Metal Halide Clusters by Host-Guest Complexation with γ-Cyclodextrin: Toward Nontoxic Luminescent Compounds.

γ-Cyclodextrin (γ-CD) interacts in aqueous solution with octahedral halide clusters Na2[{M6X8}Cl6] (M = Mo, W; X = Br, I) to form robust inclusion supramolecular complexes [{M6X8}Cl6@2γ-CD]2-. Single-crystal X-ray diffraction analyses revealed two conformational organizations within the adduct depending on the nature of the inner halide X within the {M6X8} core. Using 35Cl NMR and UV-vis as complementary techniques, the kinetics of the hydrolysis process were shown to increase with the following order: {W6I8} < {W6Br8} ≈ {Mo6I8} < {Mo6Br8}. The complexation with γ-CD drastically enhances the hydrolytic stability of luminescent [{M6X8}Cl6]2- cluster-based units, which was quantitatively proved by the same techniques. The resulting host-guest complexation provides a protective shell against contact with water and offers promising horizons for octahedral clusters in biology as revealed by the low dark cytotoxicity and cellular uptake.

Effect of potassium salts on the structure of γ-cyclodextrin MOF and the encapsulation properties with thymol.

BACKGROUND: Thymol is a natural essential oil with strong volatility, low solubility, poor dispersion, strong irritation, and an unpleasant smell, which often requires appropriate porous materials to encapsulate thymol during the application process. However, the encapsulation efficiency of thymol in inclusion complexes is low, and new methods of encapsulation need to be developed. In the present study, the encapsulation capacity, storage stability, and antibacterial activity of thymol were investigated using γ-cyclodextrin (γ-CD) metal-organic frameworks (MOFs) by cocrystallization and high-temperature adsorption methods. The effect of different potassium salts (i.e. KOH, KCl, and KAc) on the structure and complexation of γ-CD-MOFs was also analyzed. RESULTS: Compared with γ-CD, the thymol encapsulation capacity of γ-CD-MOFs was increased by two- to three-fold, with the encapsulation content following the order: KAc-γ-CD-MOF (293.8 mg g-1 ) > KOH-γ-CD-MOF (287.7 mg g-1 ) > KCl-γ-CD-MOF (249.3 mg g-1 ). The anions in the solution participate in the coordination and influence the symmetry relationship between atoms and ions. This explains the differences in both the three-dimensional γ-CD-MOF structure and the thymol encapsulation amount, as well as the high storage stability of thymol. CONCLUSION: The in vitro release kinetics and antibacterial experiments showed that the inclusion complexes prepared by γ-CD-MOFs had higher stability, sustainability, and antibacterial activity, which suggests that it is an excellent complex material for industrial and agricultural applications. © 2022 Society of Chemical Industry.

Preparation and Spectroscopic Characterization of Inclusion Complexes of 3D Ball-Milled Rifampicin with ß-cyclodextrin and γ-cyclodextrin : 3D Ball-Milled Rifampicin with ß-cyclodextrin and γ-cyclodextrin.

Rifampicin (RFP) solutions, intended to reduce incidence of prosthetic graft infection, were prepared as three-dimensional ground mixtures (3DGMs) using ß-cyclodextrin (ßCD) and γ-cyclodextrin (γCD) and characterized for their spectroscopic properties and solubility. Phase solubility diagrams revealed that 3DGMs (RFP/ßCD and RFP/γCD) produced a complex at 1:1 molar ratio. Pulsed field gradient nuclear magnetic resonance experiments indicated that the diffusion coefficients for RFP/ßCD and RFP/γCD were similar to the respective diffusion coefficients for ßCD and γCD. Rotating-frame Overhauser effect spectroscopy NMR spectra revealed the existence of a new exchanger peak for RFP/γCD, suggesting an intermolecular interaction different from that of RFP/ßCD. Differential scanning calorimetry confirmed the presence of endothermic peak at 191 °C indicating the manifestation of RFP in the inclusion complex. Interestingly, molecular interactions from the complexes, RFP/ßCD and RFP/γCD, revealed different patterns of inclusion in the 3DGMs. In RFP/ßCD, nuclear Overhauser effect spectroscopy NMR spectra indicated cross peaks for the protons of the methyl group of RFP and the protons (H-5 and H-6) in the ßCD cavity. The methyl group of RFP interacted with the narrow rim of ßCD. With RFP/γCD, cross peaks were due to the protons of the methyl group of RFP and the protons of the cavity of γCD suggesting multiple inclusion patterns. The observed multiple cross peaks affirm the inclusion of RFP into the CD cavity which enhanced its solubility by 1.6-2.0-fold when prepared as 3DGMs as RFP/ßCD and RFP/γCD, respectively.

Application of γ-cyclodextrin-lysozyme as host materials for encapsulation of curcumin: characterization, stability, and controlled release properties.

BACKGROUND: In this study, a safe and relatively stable γ-cyclodextrin-lysozyme (γ-CD-Lys) was synthesized using epichlorohydrin as the cross-linking agent, and curcumin was successfully encapsulated in γ-CD-Lys. RESULTS: The successful Lys grafting onto γ-CD can be demonstrated by a high grafting ratio (79.02%) and was further confirmed by Fourier transform infrared (FTIR) band shifts and the new signal obtained at δ 2.75 in proton nuclear magnetic resonance. The encapsulation efficiency value of γ-CD-Lys was 76.74%, and the successful encapsulation of curcumin into γ-CD-Lys was confirmed by crystal structure change, increased melting point, and FTIR band shifts. The intermolecular bonds results suggested that associative forces between curcumin and γ-CD-Lys were electrostatic interaction, hydrogen bonds interaction, and hydrophobic interaction. The designed nanoparticles had excellent stability at low pH and low salt concentration. The release rate of these nanoparticles was inhibited in simulated gastric conditions, whereas it increased significantly in intestinal media. Simulated gastrointestinal digestion experiments further confirmed that nanoparticles showed higher bioaccessibility (86.05%) compared with curcumin (58.82%). CONCLUSION: Overall, our study showed that the nanoparticles were highly promising for delivering curcumin because of their enhanced functional attributes and stabilization in acid or low salt environments. Also, it was an excellent wall material for targeting hydrophobic bioactive compounds in the intestinal tract via oral administration. © 2022 Society of Chemical Industry.

Self-assembled γ-cyclodextrin as nanocarriers for enhanced ocular drug bioavailability.

Cyclodextrins (CDs) are widely used in pharmaceutical products for improving the solubility and bioavailability of drugs through the formation of water-soluble inclusion complexes. Among natural CDs, γ-cyclodextrin (γCD) has the highest water solubility, largest cavity size, and most favorable toxicological profile. γCD can form inclusion complexes with a wide variety of drugs. In aqueous solution, γCD tends to self-assemble to form aggregates, leading to formation of both nano- and microparticles. The self-assembled γCD molecules can increase the solubility and enhance drug permeability through biological membranes, consequently improving drug bioavailability. This promising drug delivery platform is well tolerated, and it has low ocular toxicity. Clinical studies have shown that this nanocarrier can enhance topical drug delivery to both the anterior and posterior segment of the eye. The present article reviews the physicochemical properties of γCD and its derivatives, their toxicological profiles, the γCD solubilization of drugs, and methods for enhancing drug/γCD complexes and their aggregates. Additionally, examples of self-assembled drug/γCD complexes in ophthalmic preparations are discussed.