Γ-cyclodextrin Inclusion Complexes Research Articles

Exploring oral drug delivery: In vitro release and mathematical modeling of hydrophobic drug (Na-L-thyroxine) and its cyclodextrin inclusion complex in chitosan microparticles

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 β-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.

Inhibition of the SARS-CoV-2 Main Protease by Isoquercitrin γ-Cyclodextrin Inclusion Complex Formulations: A Biochemical and In Silico Study

The main protease (Mpro) of SARS-CoV-2 is a well-established drug target for rational drug design of COVID-19 inhibitors. To address the serious challenge of COVID-19, we have performed biochemical inhibition screens with recombinantly expressed SARS-CoV-2 main protease (Mpro). A fluorescent assay was used to identify the flavonoid isoquercitrin as an Mpro inhibitor. Both isoquercitrin encapsulated in γ-cyclodextrin (inclusion complex formulations) and alone inhibited SARS-CoV-2 Mpro. For isoquercitrin, a Ki value of 32 μM (IC50 = 63 μM) was obtained. Isoquercitrin γ-cyclodextrin inclusion complex formulations additionally inhibited Zika virus NS2B-NS3pro leading to an IC50 value of 98 μM. Formulations containing the other flavonoid compounds diosmetin-7-O-glucoside, hesperetin-7-O-glucoside, and naringenin-7-O-glucoside did not inhibit SARS-CoV-2 Mpro. Steady-state kinetics indicate that the inhibition mechanism of Mpro by isoquercitrin is potentially competitive. Molecular modeling studies carried out with MM/PBSA confirm the likely modes of isoquercitrin binding to both proteases. These modeling results can be used in the development of structural analogs of isoquercitrin with better inhibitory profiles and potential candidates for anti-coronavirus drugs. Since the targeted proteases are essential for viral activity, the delivery isoquercitrin-cyclodextrin inclusion complex formulations could be of great interest for the development of future antiviral drugs to target intracellular virus proteins or other components.

Study on host-guest interaction of aroma compounds/γ-cyclodextrin inclusion complexes

The hydrophobic cavity of cyclodextrin (CD) embeds aroma compounds and forms inclusion complexes (ICs). However, the possible inclusion and stabilization mechanisms remain unclear. In this study, ICs of γ-cyclodextrin (γ-CD) and 13 aroma compounds (alcohols, aldehydes, and alkenes) were prepared and characterized using Fourier transform infrared spectroscopy, X-ray diffraction, and nuclear magnetic resonance. Moreover, molecular dynamics simulation (MD) also simulated the possible complex formation, listed the interactions between the aromatic compounds and γ-CD, and explored the host-guest interaction and stabilization mechanisms. The results showed that the characteristic peaks of the aroma compounds weakened or even disappeared after inclusion, with all the ICs being crystalline. Eight aroma compounds formed ICs at a host-guest molar ratio of 1:1, while at 1:2 for the remaining compounds. The benzene ring of the aroma compounds was more likely to enter the hydrophobic cavity; the methyl group and double bond of α-terpineol entered the cavity preferentially. MD analysis revealed that for guests with similar molecular weights, the intermolecular interactions followed the following trend: alcohols > aldehydes, alkenes > aldehydes; for the same functional group distribution and unsaturation, the interaction force being positively correlated with molecular weight. The present study aimed to provide a theoretical basis for aroma embedding systems’ stable and controllable preparation.

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.

Drug-Loaded Nanocarriers Composed of Cholesteryl Oleate Crystal Cores and Multiple-Nanosheet Shells of γ-Cyclodextrin Inclusion Complex Crystals.

In this study, we prepared drug-loaded nanocarriers made of cholesteryl oleate (ChO) and γ-cyclodextrin (γ-CD). A nanosuspension (nanosuspension-I, NS-I) containing nanoparticles with a mean size of approximately 170 nm was obtained through the solvent-diffusion method using ethanol. A second nanosuspension (nanosuspension-II, NS-II), which was prepared by freeze-drying and redispersion of NS-I, exhibited an increased particle size of approximately 210 nm. Cryogenic transmission electron microscopy (cryo-TEM) and atomic force microscopy (AFM) force-distance curves indicated that the nanoparticles in NS-I were oblong and soft. However, those in NS-II were angular and stiff, and, interestingly, multiple nanosheets covered the solid-liquid interface. Synchrotron wide-angle X-ray diffraction (WAXD) analysis of NS-II indicated that the nanoparticles in it had a core-shell structure, where the ChO crystal in the inner core was covered by multiple nanosheets of ChO/γ-CD inclusion complex crystals. The X-ray peak analysis suggested that the γ-CD columns of the nanosheets were vertically stacked onto the ChO crystal interface. It was found that the nanosheets on the nanoparticle interface were formed during the freezing process. A model drug carbamazepine (CBZ) was loaded into the ChO/γ-CD nanoparticles by pre-dissolving CBZ in ethanol during the solvent-diffusion process. Cryo-TEM, 1H NMR, ζ-potentials, and synchrotron WAXD indicated that CBZ was unexpectedly loaded into the shell as a CBZ/γ-CD inclusion complex crystalline nanosheet. The specific nanosheet structure, where ChO and CBZ coexisted in the same crystal of γ-CD, could achieve CBZ loading in the nanoparticles. ChO/γ-CD nanoparticles with the unique core-shell structure are expected to perform as practical carriers for drug delivery.

Comparison of thermo-rheological, microstructural and antimicrobial properties of β- and γ-cyclodextrin inclusion complexes of cinnamon essential oil

Comparison of thermo-rheological, microstructural and antimicrobial properties of β- and γ-cyclodextrin inclusion complexes of cinnamon essential oil

Inclusion Complexes of Daidzein with Cyclodextrin-Based Metal-Organic Framework-1 Enhance Its Solubility and Antioxidant Capacity.

Daidzein, an aglycone-type isoflavone, is useful in the prevention of atherosclerotic cardiovascular diseases. However, the solubility of daidzein remains relatively low even with pharmaceutical interventions (e.g., γ-cyclodextrin inclusion complex). In the present study, daidzein-cyclodextrin-metal organic framework solid dispersion complexes were prepared by the solvent evaporation method. The physicochemical properties of the complex and its effect on the solubility of daidzein were evaluated. The enhancement effect of a cyclodextrin-metal organic framework on the antioxidant properties of daidzein was verified using a diphenyl-picrylhydrazyl radical scavenging test. Powder X-ray diffraction results showed that the characteristic diffraction peaks of daidzein and cyclodextrin-metal organic framework disappeared and new peaks (2θ = 7.1°, 16.5°) were observed. FT-IR measurements showed that the peak derived from the carbonyl group of daidzein shifted to the lower wavenumber. NOESY 1H-1H NMR showed cross peaks at the proton on the resorcinol side of daidzein and the proton (H-5, H-6) in a cyclodextrin-metal organic framework. Dissolution rate of daidzein at 5min in distilled water was 0.06% for daidzein alone while the daidzein inclusion complex was about 100%. When fasted state simulated intestinal fluid was used, the dissolution rate of the daidzein complex was about 71% compared with that of daidzein alone (~ 3.0%) at 5min. The daidzein inclusion complex improved the antioxidant capacity to ~ 1.3 times (17.8µg/mL) compared to the IC50 of daidzein alone (22.9µg/mL). Preparations of cyclodextrin-metal organic framework inclusion complexes will be a platform in developing pharmaceutical formulations to enhance the bioavailability and activity of drugs.

Synthesis, NMR Spectroscopic Study of α-, β- and γ-Cyclodextrin Inclusion Complexes of 2-Deoxyecdysone and Their Anti-inflammatory Activity

Synthesis, NMR Spectroscopic Study of α-, β- and γ-Cyclodextrin Inclusion Complexes of 2-Deoxyecdysone and Their Anti-inflammatory Activity

Encapsulation and sustained release properties of watermelon flavor and its characteristic aroma compounds from γ-cyclodextrin inclusion complexes

Encapsulation of flavors with cyclodextrins can improve their stabilities, sustained release properties, and shelf-lives. However, few studies have attempted to ascertain whether the aroma composition of the encapsulated flavor changes during preparation and release processes. This study investigated the inclusion and release behavior of a sustained release system of watermelon flavor (WF) encapsulated within γ-cyclodextrin (γ-CD). Gas chromatography-mass spectrometry (GC–MS) was employed to determine the aroma composition of encapsulated watermelon flavor. The inclusion complexes were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and wide angle X-ray diffraction (WAXD). Individual release behavior of the seven characteristic aroma compounds from γ-CD was investigated based on the Avrami equation. Results showed that the aroma composition of the encapsulated watermelon flavor was different from that of the free, although watermelon flavor was successfully encapsulated in γ-CD. Both the inclusion and release behavior of this sustained release system were significantly affected by the molecular structures of the aroma compounds. The inclusion efficiency decreased in the order of alcohols > aldehydes > esters, while the release ratio decreased with the increase of hydrophobicity, implying the different affinities of hydrophobic flavor guests to γ-CD. Therefore, the aroma composition of the encapsulated flavor during preparation and release processes cannot keep initial due to various structures of aroma compounds. This phenomenon should not be ignored to achieve prospective release patterns of flavor from inclusion complexes.

Release behavior of allyl sulfide from cyclodextrin inclusion complex of allyl sulfide under different storage conditions

The stability of allyl sulfide, an organosulfur compound present in garlic oil, in its α-, β-, and γ-cyclodextrin inclusion complexes was investigated under various storage conditions. The complexes of cyclodextrins and allyl sulfide were prepared by spray drying. The storage temperature, relative humidity, and initial moisture content of the inclusion complex had different effects on the release rate of allyl sulfide. Allyl sulfide in α-cyclodextrin complexes had a lower release rate than in β- and γ-cyclodextrin complexes at 100°C and at 50°C under 6, 40, 54, and 73% relative humidity. The initial moisture content affected only the release rate of allyl sulfide from α-cyclodextrin complexes. The release behavior of allyl sulfide can be correlated with the first-order release rate equation with a normal Gaussian distribution of free energy of activation of release rate constant. The results indicated α-cyclodextrin is a suitable material for controlled release of allyl sulfide.

Preparation, Structure and Performance of Poly(lactic acid)/Poly(lactic acid)-γ-Cyclodextrin Inclusion Complex-Poly(glycidyl methacrylate) Composites

Poly(lactic acid)-γ-cyclodextrin inclusion complex-poly(glycidyl methacrylate) (PLA-IC-PGMA) was synthesized with poly(lactic acid) (PLA) and γ-cyclodextrin inclusion complex via surface initiated atom transfer radical polymerization. Then, the PLA/PLA-IC-PGMA composite was prepared by melt blending using PLA-IC-PGMA as additive. Structure and properties of PLA-IC-PGMA and PLA/PLA-IC-PGMA composites were confirmed by X-ray diffraction patterns, 1H nuclear magnetic resonance spectroscopy, Fourier transform infrared spectra, X-ray photoelectron spectroscopy, thermogravimetric analysis, differential scanning calorimetry (DSC), polarized optical microscopy, rheological analysis, etc. Mechanical testing analysis showed that the tensile strength, elongation at break, and impact strength of PLA/(1 wt%) PLA-IC-PGMA composites were improved by 2.3%, 10.8%, and 52.5%, respectively, compared with pure PLA. Scanning electron microscopy analysis demonstrated that the toughness of PLA/PLA-IC-PGMA composite was improved. The results of DSC and TG showed that the cold crystallization peak of PLA composites after the addition of PLA-IC-PGMA disappeared, and its crystallinity was increased by 25% compared with PLA. Furthermore, the thermal stability of PLA/PLA-IC-PGMA composite was improved. Dynamic mechanical analysis showed that the glass transition temperature of PLA/PLA-IC-PGMA composites decreased by 8 °C, which indicated that the flexibility of the chain of PLA was greatly improved. Therefore, the addition of PLA-IC-PGMA improved the comprehensive performance of PLA.

Inclusion complexes of p-hydroxybenzoic acid esters and γ-cyclodextrin

The alkyl esters of p-hydroxybenzoic acid (parabens) are commonly used as preservatives in cosmetics, food products and pharmaceutical formulations because of their wide range antimicrobial activity. However, the usage of parabens in aqueous media has been hampered, especially parabens with long alkyl chains, due to their low aqueous solubility. One approach to increase their solubility is cyclodextrins (CDs) complexation to form water-soluble inclusion complexes. γCD has the widest hydrophobic central cavity and the highest water solubility among natural CDs. Hence, inclusion complexes between γCD and parabens of various alkyl chain lengths were investigated. Results from phase-solubility studies show that methyl- and ethylparaben form various complexes of paraben/γCD (i.e. 1:1, 2:1, etc.) while the 1:1 complex was dominant in propyl- and butylparaben/γCD complex solution. Moreover, the effect of the paraben complexation on the critical aggregation concentration (cac) of γCD in aqueous solutions was determined. It was found that the longer the paraben alkyl chain was the more influence it had on the γCD cac. In pharmaceutical formulations the mixture of parabens (i.e. binary, ternary and quaternary) has been used to maximize antimicrobial effect. It is important to determine how mixtures of parabens affect the solubility of γCD and its cac values upon formation of inclusion complexes. Competition of the different parabens for a space in the γCD central cavity was evaluated by comparing the γCD cac values obtained in presence of the individual parabens and their mixtures.

Antibacterial electrospun zein nanofibrous web encapsulating thymol/cyclodextrin-inclusion complex for food packaging

Thymol (THY)/γ-Cyclodextrin(γ-CD) inclusion complex (IC) encapsulated electrospun zein nanofibrous webs (zein-THY/γ-CD-IC-NF) were fabricated as a food packaging material. The formation of THY/γ-CD-IC (1:1 and 2:1) was proved by experimental (X-ray diffraction (XRD), thermal gravimetric analysis (TGA), 1H NMR) and computational techniques. THY/γ-CD-IC (2:1) exhibited higher preservation rate and stability than THY/γ-CD-IC (1:1). It is worth mentioning that zein-THY/γ-CD-IC-NF (2:1) preserved much more THY as observed in TGA and stability of THY/γ-CD-IC (2:1) was higher, as shown by a modelling study. Therefore, much more THY was released from zein-THY/γ-CD-IC-NF (2:1) than zein-THY-NF and zein-THY/γ-CD-IC-NF (1:1). Similarly, antibacterial activity of zein-THY/γ-CD-IC-NF (2:1) was higher than zein-THY-NF and zein-THY/γ-CD-IC-NF (1:1). It was demonstrated that zein-THY/γ-CD-IC-NF (2:1) was most effective in inhibiting the growth of bacteria on meat samples. These webs show potential application as an antibacterial food packaging material.

Polymerization of Ternary Inclusion Complexes of Interacting Monomer Pairs with γ-Cyclodextrin

The formation of ternary inclusion complexes of γ-cyclodextrin (γ-CD) with two different pairs of interacting monomers (4-vinylpyridine (4VP) with styrenesulfonate (SS), which can interact through attractive Coulombic interactions, and styrene (S) with 2,3,4,5,6-pentafluorostyrene (PFS), which interact through quadrupole interactions) is studied. Ternary inclusion complexes are formed for both monomer pairs, but 4VP and SS are included in the complexes in approximately the same ratio as is present in solution, whereas S and PFS are preferentially included as a pair. The influence of the ternary inclusion complexation on the copolymerization was studied. For the copolymerization of 4VP with SS no significant influence was found, whereas an enhanced tendency toward alternating copolymerization was found for the copolymerization of S and PFS in the presence of γ-CD, which is ascribed to the preferential heteroinclusion of the monomers in the γ-CD cavity.

Self-healing anticorrosion coating containing 2-mercaptobenzothiazole and 2-mercaptobenzimidazole nanocapsules

γ-cyclodextrin (γ-CD) inclusion complex containing 2-mercaptobenzothiazole (MBT) or 2-mercaptobenzimidazole (MBI) as guest was prepared by precipitation method at two conditions (at room temperature and under sonic energy). Supramolecular nanocontainers were characterized by 1H-NMR, XRD, SEM, DSC and FTIR, which proves the formation of the inclusion complex where the benzyl part of MBT or MBI has been encapsulated by the hydrophobic cavity of γ-CD. Differences between 1H-NMR, FTIR and XRD spectra of physical mixtures and inclusion complex indicated formation of MBT/γ-CD and MBI/γ-CD supramolecular nanocontainers in solid phase.

Self-assembled supramolecular hydrogel based on PCL-PEG-PCL triblock copolymer and γ-cyclodextrin inclusion complex for sustained delivery of dexamethasone.

In this study, thermosensitive, water-soluble, and biodegradable triblock copolymer PCL600-PEG6000-PCL600 was used to form supramolecular hydrogel (SMGel) by inclusion complexation with γ-cyclodextrin (γ-CD). The prepared SMGel was investigated as a carrier for sustained release of dexamethasone. The triblock copolymer PCL-PEG-PCL [where PCL = polycaprolactone, PEG = poly(ethylene glycol)] was synthesized by the ring-opening polymerization method using microwave irradiation. The polymerization reaction and the copolymer structures were evaluated by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). SMGel was prepared in aqueous solution by blending an aqueous γ-CD solution with aqueous solution of PCL-PEG-PCL triblock copolymer at room temperature. The sol-to-gel transition time was measured at various concentrations of copolymer and γ-CD. As-prepared SMGel was used to prepare a sustained, controllable drug delivery system of dexamethasone sodium phosphate. The SMGel was also characterized in terms of rheological, morphological, and structural properties. Results obtained from proton nuclear magnetic resonance ( 1H-NMR) and GPC demonstrated that microwave irradiation is a simple and reliable method for synthesis of PEG-PCL copolymer. The SMGel with excellent syringability was prepared by mixing of 20% wt γ-CD and 10% wt of copolymer within 4 s. The SMGel containing 10% wt copolymer, 20% wt γ-CD, and 0.5% or 0.1% wt dexamethasone released approximately 100% and 45% of drug over up to 23 days, respectively. It could be concluded that SMGel based on self-assembly of inclusion complexes between PCL-PEG-PCL copolymer and γ-CD could be used as a basis for injectable drug delivery systems that provide sustained and controlled release of macromolecular drugs such as dexamethasone.

Tunable double-stranded inclusion complexes of γ-cyclodextrin threaded onto non-modified poly(ethylene glycol)

The formation of double-stranded inclusion complexes (ICs) between γ-cyclodextrin (γ-CD) and non-modified poly(ethylene glycol) (PEG) was reported to be of trace yield, while in the present work, tunable inclusion complexes between γ-CD and non-modified PEG were successfully prepared by choosing suitable γ-CD concentrations and PEG molecular weights. The obtained γ-CD/PEG ICs showed double-stranded structure whose yield, appearance, and forming rate were significantly affected by PEG molecular weight and temperature as revealed by means of optical microscopy, XRD, DSC, 1H NMR, and ITC. This improved understanding on how to control the formation of double-stranded inclusion complexes should be very helpful for preparation of more sophisticated molecular machines.

Electron Injection and Energy-Transfer Properties of Spiropyran–Cyclodextrin Complexes Coated onto Metal Oxide Nanoparticles: Toward Photochromic Light Harvesting

The photochromic and spectroscopic properties of spiropyran−γ-cyclodextrin inclusion complexes coated onto the surface of zirconia and titania nanoparticles (NPs) are examined. After ultraviolet (UV) irradiation, the colorless spiropyran (SP) isomer contained within the cyclodextrin (CD) is converted to the colored merocyanine (MC) isomer, which absorbs light in the 400–600 nm region. A significant increase in the excited-state lifetime for MC-CD on zirconia NPs (τMC = 1.32 ns) is observed compared to MC in solution (τMC = 0.21 ns), indicating that MC → SP photoisomerisation is hindered by the surrounding CD. Excitation of MC-CD on titania NPs results in electron injection into the titania conduction band with a quantum yield of 0.70. Excitation of MC-CD on zirconia NPs when a squaraine-based dye sensitizer is also attached to the NP surface results in energy transfer to the dye sensitizer with a quantum yield of 0.65. The prolonged excited-state lifetime of the encapsulated MC-CD is responsible for the h...

Effect of γ-Cyclodextrin Inclusion Complex on the Absorption of R-α-Lipoic Acid in Rats.

R-α-lipoic acid (RLA) is an endogenous organic acid, and works as a cofactor for mitochondrial enzymes and as a kind of antioxidant. Inclusion complexes of RLA with α-, β- or γ-cyclodextrins (CD) were prepared and orally administered as a suspension to rats. Among them, RLA/γ-CD showed the highest plasma exposure, and its area under the plasma concentration-time curve (AUC) of RLA was 2.2 times higher than that after oral administration of non-inclusion RLA. On the other hand, the AUC after oral administration of non-inclusion RLA and RLA/γ-CD to pylorus-ligated rats did not differ. However, the AUC after intraduodenal administration of RLA/γ-CD was 5.1 times higher than that of non-inclusion RLA, and was almost comparable to the AUC after intraduodenal administration of RLA-Na solution. Furthermore, the AUC after intraduodenal administration of RLA/γ-CD was not affected by biliary ligation or co-administration of an amylase inhibitor. These findings demonstrated that RLA was absorbed from the small intestine effectively when orally administered as a γ-CD inclusion complex, which could be easily dissolved in the lumen of the intestine. In conclusion, γ-CD inclusion complex is an appropriate formulation for supplying RLA as a drug or nutritional supplement with respect to absorption.

Antipyrine–gamma cyclodextrin inclusion complex: Molecular modeling, preparation, characterization and cytotoxicity studies

Molecular docking, semi-empirical and molecular dynamics studies were conducted for α, β and γ-cyclodextrin-associated inclusion complexes of antipyrine. The results of molecular modeling were systematically analyzed to determine the stability of inclusion complexes. In preliminary computational screening, β and γ-cyclodextrin inclusion complexes of antipyrine were found to be more stable as compared to α-cyclodextrin based on docking score and binding free energies. Further, inclusion complex of antipyrine with γ-cyclodextrin was prepared by freeze drying method. Formation of the inclusion complex was investigated by solid state characterization techniques such as thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy. The changes observed in decomposition temperature, diffractogram, vibrational frequencies and morphological appearance confirmed the formation of inclusion complex. In addition, results from 1H NMR and 2D NOESY studies supported the inclusion phenomenon. The results obtained from computational studies were found to be in consistent with experimental data to ascertain the encapsulation of antipyrine into γ-cyclodextrin. The inclusion complex was found to be non-toxic toward MDCK-1 cell lines. Thus, this approach may be helpful in the formulation of drug molecules using cyclodextrins.