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γ-Cyclodextrin (γ-CD) is an attractive material among the natural cyclodextrins owing to its excellent properties. γ-CD is primarily produced from starch by γ-cyclodextrin glycosyltransferase (γ-CGTase) in a controlled system. However, difficulty in separation and low conversion rate leads to high production costs for γ-CD. In this study, γ-CGTase from Bacillus sp. G-825-6 STB17 was used in γ-CD production from cassava starch. With the introduction of sodium tetraphenylborate (NaBPh4), the total conversion rate was promoted from an initial 18.07 % to 50.49 % and the γ-CD ratio reached 78.81 % with a yield of 39.79 g/L. Furthermore, the mechanism was conducted via the determination of binding constant, which indicated that γ-CD exhibited much stronger binding strength with NaBPh4 than ß-CD. The reformation of water molecules and the chaotropic effect might be the main driving forces for the interaction. Additionally, the conformations of CD complexes were depicted by NMR and molecular docking. The results further verified different binding patterns between CDs and tetraphenylborate ions, which might be the primary reason for the specific binding. This system not only guides γ-CD production with an efficient and easy-to-remove production aid but also offers a new perspective on the selection of complexing agents in CD production.

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AIM: Our goal was to investigate the use of Cyclodextrin in creating an aqueous extract of Cinnamon with a high content of its bioactive ingredients, validated by cell-based assays. BACKGROUND: Due to their safety and cost-effectiveness, natural compounds have garnered attention for cancer therapy, which often faces challenges related to drug toxicity and resistance. Cinnamon (Cinnamomum verum; also known as Ceylon Cinnamon) is a commonly used spice with a history in folk medicine for treating various ailments. However, its active ingredients suffer from poor solubility, stability, and bioavailability, which limits its use and benefits. OBJECTIVE: We prepared γCyclodextrin (γCD)-assisted aqueous extract of Cinnamon (CD-CIN) and compared its activity with the DMSO extract (DM-CIN). METHODS: The cells were exposed to CD-CIN and DM-CIN extracts under normal and stressed (oxidative, metal, and hypoxic) conditions and then analyzed for stress and cancerous phenotypes using various molecular assays. RESULTS: We found that CD-CIN possesses considerable anticancer activity that involves the activation of tumor suppressor proteins and DNA damage response. Low, non-toxic concentrations of DM-CIN and CD-CIN caused comparable inhibition of migration and invasion capability of cells, supported by molecular marker analyses. Furthermore, protection against oxidative, metal, and hypoxia stress, as well as induction of differentiation, was recorded in both DM-CIN and CD-CIN treated cells, as compared to the control. CONCLUSION: We report CD-CIN as a new economic and easy Cinnamon-derived resource that possesses considerable anticancer and antistress activities and hence warrants further chemical, in vitro, and in vivo studies.

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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.

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Cyclodextrin-based metal-organic framework (CD-MOF) has been widely used in various delivery systems due to its excellent edibility and high drug loading capacity. However, its typically bulky size and high brittleness in aqueous solutions pose significant challenges for practical applications. Here, we proposed an ultrasonic-assisted method for rapid synthesis of uniformly-sized nanoscale CD-MOF, followed by its hydrophobic modification through ester bond cross-linking (Nano-CMOF). Proper ultrasound treatment effectively reduced particle size to nanoscale (393.14 nm). Notably, carbonate ester cross-linking method significantly improved water stability without altering its cubic shape and high porosity (1.3 cm3/g), resulting in a retention rate exceeding 90% in various media. Furthermore, the loading of quercetin did not disrupt cubic structure and showcased remarkable storage stability. Nano-CMOF achieved controlled release of quercetin in both aqueous environments and digestion. Additionally, Nano-CMOF demonstrated exceptional antioxidant (free radical scavenging 82.27%) and biocompatibility, indicating its significant potential as novel nutritional delivery systems in food and biomedical fields.

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To address the issue of bacterial growth on fresh-cut fruits, this paper reports the synthesis of nanosized γ-cyclodextrin metal-organic frameworks (CD-MOFs) using an ultrasound-assisted method and their application as carriers of limonene for antibacterial active packaging. The effects of the processing parameters on the morphology and crystallinity of the CD-MOFs are investigated, and the results prove that the addition of methanol is the key to producing nanosized CD-MOFs. The limonene loading content of the nanosized CD-MOFs can reach approximately 170 mg g-1. The sustained-release behaviors of limonene in the CD-MOFs are evaluated. Molecular docking simulations reveal the distribution and binding sites of limonene in the CD-MOFs. CD-MOFs are deposited on the surfaces of polycaprolactone (PCL) nanofibers via an immersion method, and limonene-loaded CD-MOF@PCL nanofibers are prepared. The morphology, crystallinity, thermal stability, mechanical properties, and antibacterial activity of the nanofibers are also studied. The nanofiber film effectively inhibits bacterial growth and prolongs the shelf life of fresh-cut apples. This study provides a novel strategy for developing antibacterial active packaging materials based on CD-MOFs and PCL nanofibers.

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Na-l-Thyroxine (Na-l-Thy) is a frequently prescribed synthetic hormone for hypothyroidism treatment. Despite its efficacy, its hydrophobic nature poses a challenge for achieving optimal bioavailability. To address this, researchers explored various delivery methods, including micro-formulations and nano-formulations, for precise and prolonged release of hydrophobic and hydrophilic drugs. In this study, we developed micro-formulations with cyclodextrin and chitosan. Docking studies identified γ-cyclodextrin as the preferred option for forming a stable complex with Na-l-Thyroxine compared to α, and ß-cyclodextrins. Two micro-formulations were prepared compared: Na-l-Thyroxine loaded on chitosan (CS + Na-l-Thy) and Na-l-Thyroxine and γ-cyclodextrin inclusion complex (IC) loaded on chitosan (CS + IC). CS + IC exhibited superior encapsulation efficiency (91.25 %) and loading capacity (18.62 %) compared to CS + Na-l-Thy (encapsulation efficiency: 70.24 %, loading capacity: 21.18 %). Characterization using FTIR, SEM, and TGA validated successful encapsulation of Na-l-Thy in spherical microparticles with high thermal stability. In-vitro release studies at pH 1.2 and 7.4 showed that the CS + IC microparticles displayed gradual, consistent drug release compared to CS + Na-l-Thy -Thy. Both formulations showed faster release at pH 1.2 than at pH 7.4. Reaction kinetics analysis of release studies of CS + Na-l-Thy and CS + IC were best described by Higuchi kinetic model and Korsemeyer-Peppas kinetic model respectively. This study suggests that the CS + IC microparticles are an effective and stable delivery system for sustained release of hydrophobic Na-l-Thy.

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Multifunctional packaging films that monitor and maintain fish freshness hold significant potential for use in the food industry. This study introduces a multifunctional intelligent packaging film comprising alizarin (ALI)-embedded cubic γ-cyclodextrin metal-organic frameworks (γ-CD-MOFs) (denoted as γ-CD-MOFs@ALI) in a methylcellulose/polyvinyl alcohol (MP)-based matrix to achieve colorimetric monitoring and enhanced preservation of fish freshness. The MP/γ-CD-MOFs@ALI reveals a rapid color transition in 3 min from yellow color progressively darkens to purple as the pH increases from 2.0 to 10.0. And it is proved that the as-prepared film owns high antibacterial activity against Gram-positive bacteria (S. aureus), impressive ABTS+ radical scavenging rates of 85.54 ± 1.25 %, and effective ALI sustained-release properties. The intelligent packaging film exhibits an excellent colorimetric response to total volatile basic nitrogen and provides exceptional freshness preservation performance, effectively prolonging the shelf life of Ctenopharyngodon idella (grass carp) under 25 °C to 42 h.

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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.

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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.

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A natural polysaccharide-based vehicle is facilely prepared for enantioselective loading of S-naproxen (S-NPX) and its programmed release. Cyclodextrin metal-organic frameworks (CD-MOF) are synthesized through the coordination of K+ with γ-cyclodextrin (γ-CD). Compared with R-NPX, the CD-MOF preferably combines with S-NPX, which can be confirmed by the thermodynamic calculations. The S-NPX loaded CD-MOF (CD-MOF-S-NPX) is grafted with disulfide bond (-S-S-) to improve its hydrophobicity, and the loaded S-NPX is further encapsulated in the chiral cavity of γ-CD by carboxymethyl potato starch (CPS) hydrogels. The intermolecular hydrogen bonding of the CPS hydrogels is prone to be destroyed in mildly basic media (∼pH 8.0), resulting in the swelling of the hydrogels; the -S-S- linkage in the vehicle can be cleaved in the presence of glutathione (GSH), leading to the collapse of the CD-MOF. Therefore, the programmed release of S-NPX can be achieved. Also in this work, the release kinetics is investigated, and the results indicate that the release of S-NPX is controlled by the Higuchi model.

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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.

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Anthocyanins are promising naturally occurring food preservatives for enhancing the quality of food products due to their excellent antioxidant properties. However, their low stability hinders their food packaging application. Here, we propose a facile strategy to achieve the improved stability of anthocyanins encapsulated in γ-cyclodextrin metal-organic frameworks (CD-MOFs) with an in-depth exploration of their structure-property relationships. The adsorbed anthocyanins in CD-MOFs are stabilized by multiple cooperative non-covalent interactions including hydrogen bonding and van der Waals (vdW) interactions as demonstrated by density functional theory (DFT) calculations and spectroscopy analysis. Particularly, by ion-exchange of acetate ions into the pores of CD-MOFs, the resulting CD-MOFs (CD-MOF_OAc) shows a higher anthocyanins adsorption rate with a maximum loading capacity of 83.7 % at 1 min. Besides, CD-MOF_OAc possesses the more effective protecting effect on anthocyanins with at least two-fold enhancement of stability in comparison of free anthocyanins under heating and light irradiation. The anthocyanins encapsulated CD-MOFs films for fruit freshness was validated by the Kyoho experiment. This novel encapsulation system provides a new possibility for the potential use of CD-MOFs as the encapsulating material for anthocyanins in fruit preservation.

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Since griseofulvin was marketed as a non-polyene antifungal antibiotic drug in 1958, its poor water solubility has been an issue for its wide applications, and over the last sixty years, many attempts have been made to increase its water solubility; however, a significant result has yet to be achieved. Through supercritical carbon dioxide-assisted cyclodextrin complexation with the addition of a trace amount of water-soluble polymer surfactant, the griseofulvin inclusion complex with HP-γ-cyclodextrin was prepared and confirmed. The 1:2 ratio of griseofulvin and HP-γ-cyclodextrin in the complex was determined based on its NMR study. After complexation with HP-γ-cyclodextrin, griseofulvin's water solubility was increased 477 times compared with that of griseofulvin alone, which is the best result thus far. The complex showed 90% of griseofulvin release in vitro in 10 min, in an in vivo dog pharmacokinetic study; the Cmax was increased from 0.52 µg/mL to 0.72 µg/mL, AUC0-12 was increased from 1.55 µg·h/mL to 2.75 µg·h/mL, the clearance was changed from 51.78 L/kg/h to 24.16 L/kg/h, and the half-life time was changed from 0.81 h to 1.56 h, indicating the obtained griseofulvin complex can be a more effective drug than griseofulvin alone.

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It is well known that platinum-based antineoplastic agents, including cisplatin (CP), have side effects that limit their use. Nefrotoxicity, neurotoxicity, and hemolytic anemia are the most common side effects. There are few studies on the reduction in these effects that involves nanoencapsulation; however, almost none involve cyclodextrins (CDs). Changes in the hematological and biochemical parameters of healthy Wistar rats treated with solutions of γ-cyclodextrin/resveratrol/cisplatin (γ-CD/Rv/CP) ternary complexes are investigated for the first time. They are intraperitoneally injected with γ-CD/Rv/CP solutions containing 5 mg CP/kg.b.w. Single shots were administered to six groups of Wistar rats (six individuals for every group) using γ-CD/Rv/CP, γ-CD/CP, γ-CD/Rv complexes, as well as positive- and negative-control groups, respectively. Thirty-two hematological and biochemical parameters were evaluated from blood samples and used as input variables for the principal component analysis (PCA) discrimination of the groups. The best protection was obtained for the γ-CD/Rv/CP ternary complex, which determined closer biochemical values to the control group. These values significantly differ from those of the γ-CD/CP treated group, especially for the IP, UA, and T-Pro kidney-related biochemical parameters. This finding proves the beneficial influence of Rv during CP administration through CD-based carriers.

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Dairy protein hydrolysates possess a broad spectrum of bioactivity and hypoallergenic properties, as well as pronounced bitter taste. The bitterness is reduced by complexing the proteolysis products with cyclodextrins (CDs), and it is also important to study the bioactivity of the peptides in inclusion complexes. Hydrolysates of whey and colostrum proteins with extensive hydrolysis degree and their complexes with ß/γ-CD were obtained in the present study, and comprehensive comparative analysis of the experimental samples was performed. The interaction of CD with peptides was confirmed via different methods. Bioactivity of the initial hydrolysates and their complexes were evaluated. Antioxidant activity (AOA) was determined by fluorescence reduction of fluorescein in the Fenton system. Antigenic properties were studied by competitive enzyme immunoassay. Antimutagenic effect was estimated in the Ames test. According to the experimental data, a 2.17/2.78-fold and 1.45/2.14-fold increase in the AOA was found in the ß/γ-CD interaction with whey and colostrum hydrolysates, respectively. A 5.6/5.3-fold decrease in the antigenicity of whey peptides in complex with ß/γ-CD was detected, while the antimutagenic effect in the host-guest systems was comparable to the initial hydrolysates. Thus, bioactive CD complexes with dairy peptides were obtained. Complexes are applicable as a component of specialized foods (sports, diet).

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Cyclodextrins (CDs) are natural cyclic oligosaccharides with a relatively hydrophobic cavity and a hydrophilic outer surface. In this study, alpha (α-), beta (ß-) and gamma (γ-) CD particles were prepared by directly using α-, ß-, and γ-CDs as monomeric units and divinyl sulfone (DVS) as a crosslinker in a single-step via reverse micelle microemulsion crosslinking technique. Particles of p(α-CD), p(ß-CD), and p(γ-CD) were perfectly spherical in sub- 10 µm size ranges. The prepared p(CD) particles at 1.0 mg/mL concentrations were found biocompatible with > 95 % cell viability against L929 fibroblasts. Furthermore, p(α-CD) and p(ß-CD) particles were found non-hemolytic with < 2 % hemolysis ratios, whereas p(γ-CD) particles were found to be slightly hemolytic with its 2.1 ± 0.4 % hemolysis ratio at 1.0 mg/mL concentration. Furthermore, a toxic compound, Bisphenol A (BPA) and a highly antioxidant polyphenol, curcumin (CUR) complexation with α-, ß-, and γ-CD molecules was investigated via Electrospray-Ion Mobility-Mass Spectrometry (ESI-IM-MS) and tandem mass spectrometry (MS/MS) analysis. It was determined that the most stable noncovalent complex was in the case of ß-CD, but the complex stoichiometry was changed by the hydrophobic nature of the guest molecules. In addition, BPA and CUR were separately loaded into prepared p(CD) particles as active agents. The drug loading and release studies showed that p(CD) particles possess governable loading and releasing profiles.

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In this study, we fabricated γ-cyclodextrin (γCD)-based nanoparticles (NPs) for dual antitumor therapy. First, γCD (the backbone biopolymer) was chemically conjugated with low-molecular-weight hyaluronic acid (HA; a tumoral CD44 receptor-targeting molecule) and 3-(diethylamino)propylamine (DEAP; a pH-responsive molecule), termed as γCD-(DEAP/HA). The obtained γCD-(DEAP/HA) self-assembled in aqueous solution, producing the γCD-(DEAP/HA) NPs. These NPs efficiently entrapped paclitaxel (PTX; an antitumor drug) and triiron dodecacarbonyl (FeCO; an endogenous cytotoxic gas molecule) via hydrophobic interactions between PTX and FeCO with the unprotonated DEAP molecules in γCD-(DEAP/HA) and a possible host-guest interaction in the γCD rings. The release of PTX and FeCO from the NPs resulted from particle destabilization at endosomal pH, probably owing to the protonation of DEAP in the NPs. In vitro studies using MCF-7 tumor cells demonstrated that these NPs were efficiently internalized by the cells expressing CD44 receptors and enhanced PTX/FeCO-mediated tumor cell apoptosis. Importantly, local light irradiation of FeCO stimulated the generation of cytotoxic CO, resulting in highly improved tumor cell death. We expect that these NPs have potential as dual-modal therapeutic candidates with enhanced antitumor activity in response to acidic pH and local light irradiation.

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Lactonic sophorolipid (LSL) exhibits numerous surfactant activities, such as emulsification, wetting action, dispersion effect, and oil-washing activities. Nevertheless, LSLs have poor water solubility, which restrains their application in the petroleum industry. In this research, a new compound, lactonic sophorolipid cyclodextrin metal-organic framework (LSL-CD-MOFs), was obtained by loading LSL into γ-cyclodextrin metal-organic frameworks (γ-CD-MOFs). The LSL-CD-MOFs were characterized by N2 adsorption analysis, X-ray powder diffraction analysis, Fourier transform infrared spectroscopy, and thermogravimetric analysis. Loading LSL into γ-CD-MOFs significantly increased the apparent water solubility of LSL. However, the critical micelle concentration of LSL-CD-MOFs was similar to that of LSL. Furthermore, LSL-CD-MOFs effectively reduced the viscosities and improved the emulsification indices of oil-water mixtures. Oil-washing tests, which were conducted using oil sands, revealed that the LSL-CD-MOFs yielded an oil-washing efficiency of 85.82 % ± 2.04 %. Overall, γ-CD-MOFs are promising carriers for LSL, and LSL-CD-MOFs are a potential, low-cost, new, green surfactant for enhanced oil recovery.

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Enantioselective labeling of important bioactive molecules in complex biological environments by artificial receptors has drawn great interest. From both the slight difference of enantiomers' physicochemical properties and inherently complexity in living organism point of view, it is still a contemporary challenge for preparing practical chiral device that could be employed in the model animal due to diverse biological interference. Herein, we introduce γ-cyclodextrin onto graphene oxide for fabricating γ-cyclodextrin and graphene oxide assemblies, which provided an efficient nanoplatform for chiral labelling of D-phenylalanine with higher chiral discrimination ratio of KD/KL = 8.21. Significantly, the chiral fluorescence quenching effect of this γ-CD-GO nanoplatform for D-phenylalanine enantiomer in zebrafish was 7.0-fold higher than L-isomer, which exhibiting real promise for producing practical enantio-differentiating graphene-based systems in a complex biological sample.

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Diosmin (DSN) is found mainly in citrus fruits, and has potent antioxidant effects. This study aimed to evaluate pharmacokinetics of diosmetin-7-glucoside-γ-cyclodextrin (DIOSG-CD) inclusion complex. The area under the curve values from AUC0-24 of DIOSG-CD, prepared by reacting DSN and naringinase with γ-CD, were approximately 800-fold higher than those of DSN following their administration in Sprague-Dawley rats.

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