Preparation and comparison of binary and ternary inclusion complexes of aripiprazole using L-arginine/lysine and MßCD/HPßCD by using different molar ratios.

Aripiprazole (ARI), an antipsychotic having low solubility and stability. To overcome this, formation of binary and ternary using inclusion complexes of Methyl-ß-cyclodextrin (MßCD) /Hydroxy propyl beta cyclodextrin (HPßCD) and L-Arginine (ARG)/ Lysine (LYS) are analyzed by dissolution testing and phase stability study along with their complexation efficacy and solubility constants made by physical mixing. Inclusion complexes with ARG were better than LYS and prepared by solvent evaporation and lyophilization method as well. They are characterized by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (AT-FTIR), X-ray powder diffractometry (XRD), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM) and Thermal gravimetric analysis (TGA). The bond shifting in AT-FTIR confirmed the molecular interactions between host and guest molecules. The SEM images also confirmed a complete change of drug morphology in case of ternary inclusion complexes prepared by lyophilization method for both the polymers. ARI: MßCD: ARG when used in the specific molar ratio of 1:1:0.27 by prepared by lyophilization method has 18 times best solubility while ARI:HPßCD:ARG was 7 times best solubility than pure drug making MßCD a better choice than HPßCD. Change in the molar ratio will cause loss of stability or solubility. Solvent evaporation gave significant level of solubility but less stability.

Adenosine Encapsulation and Characterization through Layer-by-Layer Assembly of Hydroxypropyl-ß-Cyclodextrin and Whey Protein Isolate as Wall Materials.

Adenosine, as a water-soluble active substance, has various pharmacological effects. This study proposes a layer-by-layer assembly method of composite wall materials, using hydroxypropyl-ß-cyclodextrin as the inner wall and whey protein isolate as the outer wall, to encapsulate adenosine within the core material, aiming to enhance adenosine microcapsules' stability through intermolecular interactions. By combining isothermal titration calorimetry with molecular modeling analysis, it was determined that the core material and the inner wall and the inner wall and the outer wall interact through intermolecular forces. Adenosine and hydroxypropyl-ß-cyclodextrin form an optimal 1:1 complex through hydrophobic interactions, while hydroxypropyl-ß-cyclodextrin and whey protein isolate interact through hydrogen bonds. The embedding rate of AD/Hp-ß-CD/WPI microcapsules was 36.80%, and the 24 h retention rate under the release behavior test was 76.09%. The method of preparing adenosine microcapsules using composite wall materials is environmentally friendly and shows broad application prospects in storage and delivery systems with sustained release properties.

Solving the puzzle of 2-hydroxypropyl ß-cyclodextrin: Detailed assignment of the substituent distribution by NMR spectroscopy.

2-Hydroxypropyl-ß-cyclodextrin (HPBCD) is one of the most important cyclodextrin derivatives, finding extensive applications in the pharmaceutical sector. Beyond its role as an excipient, HPBCD achieved orphan drug status in 2015 for Niemann-Pick type C disease treatment, prompting research into its therapeutic potential for various disorders. However, the acceptance of HPBCD as an active pharmaceutical ingredient may be impeded by its complex nature. Indeed, HPBCD is not a single entity with a well-defined structure, instead, it is a complex mixture of isomers varying in substituent positions and the degree of hydroxypropylation, posing several challenges for unambiguous characterization. Pharmacopoeias' methods only address the average hydroxypropylation extent, lacking a rapid approach to characterize the substituent positions on the CD scaffold. Recognizing that the distribution of substituents significantly influences the complexation ability and overall activity of the derivative, primarily by altering cavity dimensions, we present a straightforward and non-destructive method based on liquid state NMR spectroscopy to analyze the positions of the hydroxypropyl sidechains. This method relies on a single set of routine experiments to establish quantitative assignment and it provides a simple yet effective tool to disclose the substitution pattern of this complex material, utilizing easily accessible (400 MHz NMR) instrumentation.

Silibinin solubilization: combined effect of co-solvency and inclusion complex formation.

OBJECTIVE: Belonging to the class II drugs according to the biopharmaceutics classification system, silibinin (SLB) benefits from high permeability but suffers poor solubility that negatively affects the development of any delivery system. This research aimed to improve SLB solubility by combined use of co-solvency and complexation phenomena. METHODS: Solubility studies were performed using the phase solubility analysis according to the shake-flask method in the presence of ethanol and 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as a co-solvent and inclusion complexing agent, respectively. SLB release studies from chitosan nanoparticles were carried out in double-wall, diffusion cells using the optimized drug release medium. RESULTS: SLB solubility was mathematically optimized constraining to using the lowest concentrations of ethanol and HP-ß-CD. SLB solubility increased linearly with the increase of HP-ß-CD concentration. The solubility in PBS-ethanol mixtures followed a log-linear model. SLB solubility in the presence of the ethanol co-solvent and HP-ß-CD complexing agent was optimized by adopting a genetic algorithm suggesting the phosphate buffer saline solution supplemented by 6%v/v ethanol and 8 mM HP-ß-CD as an optimized medium. The optimized solution was examined to study SLB release from chitosan nanoparticles (4.5 ± 0.2% drug loading) at 37 °C under static conditions. The sigmoidal release profile of SLB from the particles indicated a combination of erosion and diffusion mechanisms governing drug release from the nanoparticles. CONCLUSION: SLB solubility in a buffered solution supplemented by ethanol co-solvent and HP-ß-CD complexing agent is a function of free drug present in the semi-aqueous media, the drug-ligand binary complex, and the drug/ligand/co-solvent ternary complex.

Regulating Tumor-Associated Macrophage Polarization by Cyclodextrin-Modified PLGA Nanoparticles Loaded with R848 for Treating Colon Cancer.

Purpose: This study aimed to develop a novel and feasible modification strategy to improve the solubility and antitumor activity of resiquimod (R848) by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-ß-CD). Methods: R848-loaded PLGA nanoparticles modified with 2-HP-ß-CD (CD@R848@NPs) were synthesized using an enhanced emulsification solvent-evaporation technique. The nanoparticles were then characterized in vitro by several methods, such as scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, particle size analysis, and zeta potential analysis. Then, the nanoparticles were loaded with IR-780 dye and imaged using an in vivo imaging device to evaluate their biodistribution. Additionally, the antitumor efficacy and underlying mechanism of CD@R848@NPs in combination with an anti-TNFR2 antibody were investigated using an MC-38 colon adenocarcinoma model in vivo. Results: The average size of the CD@R848@NPs was 376 ± 30 nm, and the surface charge was 21 ± 1 mV. Through this design, the targeting ability of 2-HP-ß-CD can be leveraged and R848 is delivered to tumor-supporting M2-like macrophages in an efficient and specific manner. Moreover, we used an anti-TNFR2 antibody to reduce the proportion of Tregs. Compared with plain PLGA nanoparticles or R848, CD@R848@NPs increased penetration in tumor tissues, dramatically reprogrammed M1-like macrophages, removed tumors and prolonged patient survival. Conclusion: The new nanocapsule system is a promising strategy for targeting tumor, reprogramming tumor -associated macrophages, and enhancement immunotherapy.

On Interactions of Sulfamerazine with Cyclodextrins from Coupled Diffusometry and Toxicity Tests.

This scientific study employs the Taylor dispersion technique for diffusion measurements to investigate the interaction between sulfamerazine (NaSMR) and macromolecular cyclodextrins (ß-CD and HP-ß-CD). The results reveal that the presence of ß-CD influences the diffusion of the solution component, NaSMR, indicating a counterflow of this drug due to solute interaction. However, diffusion data indicate no inclusion of NaSMR within the sterically hindered HP-ß-CD cavity. Additionally, toxicity tests were conducted, including pollen germination (Actinidia deliciosa) and growth curve assays in BY-2 cells. The pollen germination tests demonstrate a reduction in sulfamerazine toxicity, suggesting potential applications for this antimicrobial agent with diminished adverse effects. This comprehensive investigation contributes to a deeper understanding of sulfamerazine-cyclodextrin interactions and their implications for pharmaceutical and biological systems.

Dextrin-assisted gel electromembrane extraction of chiral drugs: Improving the extraction efficiency and investigation of enantioselectivity of extraction.

The present study investigates the use of dextrins (maltodextrin, ß-cyclodextrin, and hydroxypropyl-ß-cyclodextrin) to improve the efficiency of the agarose-based gel electromembrane extraction technique for extracting chiral basic drugs (citalopram, hydroxyzine, and cetirizine). Additionally, it examines the enantioselectivity of the extraction process for these drugs. To achieve these, dextrins were incorporated into either the sample solution, the membrane, or the acceptor solution, and then the extraction procedure was performed. Enantiomers were separated and analyzed using a capillary electrophoresis device equipped with a UV detector. The results obtained under the optimal extraction conditions (sample solution pH: 4.0, acceptor solution pH: 2.0, gel membrane pH: 3.0, agarose concentration: 3 % w/v, stirring rate: 1000 rpm, gel thickness: 4.4 mm, extraction voltage: 62.3 V, and extraction time: 32.1 min) indicated that incorporating dextrins into either the sample solution, membrane or the acceptor solution enhances extraction efficiency by 17.3-23.1 %. The most significant increase was observed when hydroxypropyl-ß-cyclodextrin was added to the acceptor solution. The findings indicated that the inclusion of hydroxypropyl-ß-cyclodextrin in the sample solution resulted in an enantioselective extraction, yielding an enantiomeric excess of 6.42-7.14 %. The proposed method showed a linear range of 5.0-2000 ng/mL for enantiomers of model drugs. The limit of detection and limit of quantification for all enantiomers were found to be < 4.5 ng/mL and <15.0 ng/mL, respectively. Intra- and inter-day RSDs (n = 4) were less than 10.8 %, and the relative errors were less than 3.2 % for all the enantiomers. Finally, the developed method was successfully applied to determine concentrations of enantiomers in a urine sample with relative recoveries of 96.8-99.2 %, indicating good reliability of the developed method.

Novel nano-encapsulated limonene: Utilization of drug-in-cyclodextrin-in-liposome formulation to improve the stability and enhance the antioxidant activity.

Drug-in-cyclodextrin-in-liposome (DCL) combines advantages of cyclodextrin and liposome. Here, DCL formulation was successfully prepared to encapsulate limonene (Lim), whose characterization revealed that particle size was 147.5 ± 1.3 nm and zeta potential was -48.7 ± 0.8 mV. And the complexation mechanism of Lim/HP-ß-CD inclusion complex (the intermediate of DCL) was analyzed by molecular dynamics simulation, showing that Lim was entrapped into the cavity of HP-ß-CD through electrostatic and hydrophobic interaction with a molar ratio of 1:1. Notably, DCL formulation not only reduced Lim volatilization in 25℃, but also enhanced the free radical (DPPH· and ABTS·+) scavenging ability of Lim. In summary, Lim-DCL formulation improved the stability and enhanced the antioxidant activity of Lim. DCL nanocarrier system is suitable to preserve volatile and hydrophobic compounds, enlarging their application in pharmaceutics industries.

A novel cationic ß-cyclodextrin decorated with a choline-like pendant exhibits Iodophor, Mucoadhesive and bactericidal properties.

Iodine is a vital microelement and a powerful antiseptic with a rapid and broad spectrum of action. The development of iodophor compounds to improve the solubility and stability of iodine is still challenging. Here, we report the synthesis of a novel cationic ß-cyclodextrin bearing a choline-like pendant (ß-CD-Chol) designed to complex and deliver iodine to bacterial cells. The characterization of ß-CD-Chol and the investigation of the inclusion complex with iodine were performed by NMR spectroscopy, mass spectrometry, UV-vis spectrophotometry, isothermal titration calorimetry, and dynamic light scattering. The functionalization with the positively charged unit conferred improved water-solubility, mucoadhesivity, and iodine complexation efficiency to the ß-CD scaffold. The water-soluble ß-CD-Chol/iodine complex efficiently formed both in solution and by solid-vapor reaction. The solid complex exhibited a significant stability for months. Iodine release from the inclusion complex was satisfactory and the bactericidal activity was proved against a Staphylococcus epidermidis strain. The absence of cytotoxicity tested on human keratinocytes and the improved mucoadhesivity make ß-CD-Chol a promising drug delivery system and an appealing iodophor candidate for iodine-based antisepsis including mucosa disinfection.

Functionalization of cotton nonwoven with cyclodextrin/lawsone inclusion complex nanofibrous coating for antibacterial wound dressing.

Functionalizing cotton to induce biological activity is a viable approach for developing wound dressing. This study explores the development of cotton-based wound dressing through coating with biologically active nanofibers. Bioactive compounds like lawsone offer dual benefits of wound healing and infection prevention, however, their limited solubility and viability hinder their applications. To address this, Hydroxypropyl-beta-cyclodextrin (HP-ß-CD) and Hydroxypropyl-gamma-cyclodextrin (HP-γ-CD) were employed. Inclusion complexations of CD/lawsone were achieved at 2:1 and 4:1 M ratios, followed by the fabrication of CD/lawsone nanofibrous systems via electrospinning. Phase solubility studies indicated a twofold increase in lawsone water-solubility with HP-ß-CD. Electrospinning yielded smooth and uniform nanofibers with an average diameter of ∼300-700 nm. The results showed that while specific crystalline peaks of lawsone are apparent in the samples with a 2:1 M ratio, they disappeared in 4:1, indicating complete complexation. The nanofibers exhibited ∼100 % loading efficiency of lawsone and its rapid release upon dissolution. Notably, antibacterial assays demonstrated the complete elimination of Escherichia coli and Staphylococcus aureus colonies. The CD/lawsone nanofibers also showed suitable antioxidant activity ranging from 50 % to 70 %. This integrated approach effectively enhances lawsone's solubility through CD complexation and offers promise for bilayer cotton-based wound dressings.

Enhancement of the solubility and oral bioavailability of altrenogest through complexation with hydroxypropyl-ß-cyclodextrin.

Altrenogest (ALT), a synthetic progestogen, serves a critical role in estrus synchronization among animals like gilts and mares. However, its practical application in animal husbandry is hampered due to its poor solubility and limited oral bioavailability. To address this challenge, a solvent evaporation method was employed to create an inclusion complex of ALT with hydroxypropyl-ß-cyclodextrin (ALT/HP-ß-CD). The formation of this inclusion complex was confirmed by scanning electron microscopy, power X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and docking calculations. In addition, we further conducted pharmacokinetic investigation involving gilts, comparing ALT/HP-ß-CD inclusion complex to an ALT oral solution. The physicochemical characterization results unveiled a transformation of ALT's crystal morphology into an amorphous state, with ALT effectively entering the cavity of HP-ß-CD. Compared with ALT, the solubility of ALT/HP-ß-CD inclusion complex increased by 1026.51-fold, and its dissolution rate demonstrated significant improvement. Pharmacokinetic assessments further revealed that the oral bioavailability of ALT/HP-ß-CD inclusion complex surpassed that of the ALT oral solution, with a relative bioavailability of 114.08 %. In conclusion, complexation with HP-ß-CD represents a highly effective approach to improve both the solubility and oral bioavailability of ALT.

Mechanistic insight of α-mangostin encapsulation in 2-hydroxypropyl-ß-cyclodextrin for solubility enhancement.

α-Mangostin is the most abundant compound contained in the mangostin (Garcinia mangostana L.) plant which have been developed and proven to have many promising pharmacological effects. However, the low water solubility of α-mangostin causes limitations in its development in clinical purpose. To increase the solubility of a compound, a method currently being developed is to make drug inclusion complexes using cyclodextrins. This research aimed to use in silico techniques namely molecular docking study and molecular dynamics simulation to explore the molecular mechanism and stability of the encapsulation of α-mangostin using cyclodextrins. Two types of cyclodextrins were used including ß-cyclodextrin and 2-hydroxypropyl-ß-cyclodextrin docked against α-mangostin. From the molecular docking results, it shows that the α-mangostin complex with 2-hydroxypropyl-ß-cyclodextrin provides the lowest binding energy value of -7.99 Kcal/mol compared to ß-cyclodextrin value of -6.14 Kcal/mol. The α-mangostin complex with 2-hydroxypropyl-ß-cyclodextrin also showed good stability based on molecular dynamics simulation during 100 ns. From molecular motion, RDF, Rg, SASA, density, total energy analyzes, this complex shows increased solubility in water and provided good stability. This indicates that the encapsulation of α-mangostin with 2-hydroxypropyl-ß-cyclodextrin can increase the solubility of the α-mangostin.Communicated by Ramaswamy H. Sarma.

PCL/Yam Polysaccharide nanofibrous membranes loaded with self-assembled HP-ß-CD/ECG inclusion complexes for food packaging.

In this study, Polycaprolactone (PCL)/Yam Polysaccharide (YP) fiber membranes loaded the ultrasound-mediated assembly of 2-Hydroxypropyl-ß-cyclodextrin (HP-ß-CD)/Epicatechin gallate (ECG) inclusion complexes were prepared by electrospinning technology for food packaging. Morphology, infrared spectroscopy and X-ray diffraction results showed that the inclusion complexes were successfully assembled. With the addition of inclusion complexes, the average diameter of the fibers increased from 2480.96 to 10179.12 nm, the crystallinity decreased, the thermal stability improved, the hydrophilicity enhanced, and the water vapor permeability enhanced. Meanwhile, thermogravimetry and differential scanning calorimetry results showed that the inclusion complexes formed hydrogen bonds between the fibers, which improved the thermal stability, but the mechanical behavior suffered a certain loss. In addition, the fiber membrane could continuously release ECG within 240 h, which showed excellent antibacterial effects both in vitro and in vivo. These results indicated that the fiber film developed based on electrospinning had a broad application prospect in food packaging.

Effects of Encapsulation of Caesalpinia sappan L. with Cyclodextrins for Bovine Mastitis.

The main components of Caesalpinia sappan L. (CS) are brazilin and brazilein, which show high potential in pharmacologic applications. However, these have been drastically limited by the poor water solubility and stability. The present study investigates the formation of inclusion complexes F1, F2, and F3 between CS and ß-cyclodextrin (ßCD), hydroxypropyl-ß-cyclodextrin (HPßCD), and methyl-ß-cyclodextrin (MßCD), respectively. These complexes were characterized by Fourier transform infrared spectroscopy (FT-IR). The results showed that the highest encapsulation efficiency and loading capacity of CS extract were 44.24% and 9.67%, respectively. The solubility and stability of CS extract were significantly increased through complexation in phase solubility and stability studies. The complexes F1-F3 showed mainly significant antibacterial activities on gram-positive bacteria pathogens causing mastitis. Moreover, the expression levels of COX-2 and iNOS were significantly decreased in LPS-induced inflammatory cells at concentrations of 50 and 100 µg/mL. In addition, treatment of complex F3 (CS/MßCD) in bovine endothelial cells remarkably increased the chemokine gene expression of CXCL3 and CXCL8, which were responsible for immune cell recruitment (9.92 to 11.17 and 8.23 to 9.51-fold relative to that of the LPS-treated group, respectively). This study provides a complete characterization of inclusion complexes between CS extract and ßCD, HPßCD, and MßCD for the first time, highlighting the impact of complex formation on the pharmacologic activities of bovine mastitis.

Unraveling the Interaction of Diflunisal with Cyclodextrin and Lysozyme by Fluorescence Spectroscopy.

Understanding the interaction between the drug:carrier complex and protein is essential for the development of a new drug-delivery system. However, the majority of reports are based on an understanding of interactions between the drug and protein. Here, we present our findings on the interaction of the anti-inflammatory drug diflunisal with the drug carrier cyclodextrin (CD) and the protein lysozyme, utilizing steady-state and time-resolved fluorescence spectroscopy. Our findings reveal a different pattern of molecular interaction between the inclusion complex of ß-CD (ß-CD) or hydroxypropyl-ß-CD (HP-ß-CD) (as the host) and diflunisal (as the guest) in the presence of protein lysozyme. The quantum yield for the 1:2 guest:host complex is twice that of the 1:1 guest:host complex, indicating a more stable hydrophobic microenvironment created in the 1:2 complex. Consequently, the nonradiative decay pathway is significantly reduced. The interaction is characterized by ultrafast solvation dynamics and time-resolved fluorescence resonance energy transfer. The solvation dynamics of the lysozyme becomes 10% faster under the condition of binding with the drug, indicating a negligible change in the polar environment after binding. In addition, the fluorescence lifetime of diflunisal (acceptor) is increased by 50% in the presence of the lysozyme (donor), which indicates that the drug molecule is bound to the binding pocket on the surface of the protein, and the average distance between active tryptophan in the hydrophobic region and diflunisal is calculated to be approximately 50 Å. Excitation and emission matrix spectroscopy reveals that the tryptophan emission increases 3-5 times in the presence of both diflunisal and CD. This indicates that the tryptophan of lysozyme may be present in a more hydrophobic environment in the presence of both diflunisal and CD. Our observations on the interaction of diflunisal with ß-CD and lysozyme are well supported by molecular dynamics simulation. Results from this study may have an impact on the development of a better drug-delivery system in the future. It also reveals a fundamental molecular mechanism of interaction of the drug-carrier complex with the protein.

Solubility and Pharmacokinetic Profile Improvement of Griseofulvin through Supercritical Carbon Dioxide-Assisted Complexation with HP-γ-Cyclodextrin.

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.

Change in the Kinetic Regime of Aggregation of Yeast Alcohol Dehydrogenase in the Presence of 2-Hydroxypropyl-ß-cyclodextrin.

Chemical chaperones are low-molecular-weight compounds that suppress protein aggregation. They can influence different stages of the aggregation process-the stage of protein denaturation, the nucleation stage and the stage of aggregate growth-and this may lead to a change in the aggregation kinetic regime. Here, the possibility of changing the kinetic regime in the presence of a chemical chaperone 2-hydroxypropyl-ß-cyclodextrin (2-HP-ß-CD) was investigated for a test system based on the thermally induced aggregation of yeast alcohol dehydrogenase (yADH) at 56 °C. According to differential scanning calorimetry data, 2-HP-ß-CD did not affect the stage of the protein molecule unfolding. Dynamic light scattering data indicated changes in the aggregation kinetics of yADH during the nucleation and aggregate growth stages in the presence of the chaperone. The analysis of kinetic curves showed that the order of aggregation with respect to protein (nc), calculated for the stage of aggregate growth, changed from nc = 1 to nc = 2 with the addition of 100 mM 2-HP-ß-CD. The mechanism of 2-HP-ß-CD action on the yADH thermal aggregation leading to a change in its kinetic regime of aggregation is discussed.

Nanofibers of Glycyrrhizin/Hydroxypropyl-ß-Cyclodextrin Inclusion Complex: Enhanced Solubility Profile and Anti-inflammatory Effect of Glycyrrhizin.

Despite having a wide range of therapeutic advantages, glycyrrhizin (GL) has few commercial applications due to its poor aqueous solubility. In this study, we combined the benefits of hydroxypropyl ß-cyclodextrin (HP-ßCD) supramolecular inclusion complexes and electrospun nanofibers to improve the solubility and therapeutic potential of GL. A molecular inclusion complex containing GL and HP-ßCD was prepared by lyophilization at a 1:2 molar ratio. GL and hydroxypropyl ß-cyclodextrin inclusion complexes were also incorporated into hyaluronic acid (HA) nanofibers. Prepared NF was analyzed for physical, chemical, thermal, and pharmaceutical properties. Additionally, a rat model of carrageenan-induced hind paw edema and macrophage cell lines was used to evaluate the anti-inflammatory activity of GL-HP-ßCD NF. The DSC and XRD analyses clearly showed the amorphous state of GL in nanofibers. In comparison to pure GL, GL-HP-ßCD NF displayed improved release (46.6 ± 2.16% in 5 min) and dissolution profiles (water dissolvability ≤ 6 s). Phase solubility results showed a four-fold increase in GL solubility in GL-HP-ßCD NF. In vitro experiments on cell lines showed that inflammatory markers like IL-1ß, TNF-α, and IL-6 were significantly lower in GL-HP-ßCD NF compared to pure GL (p < 0.01 and p < 0.05). According to in vivo results, the prepared nanofiber exhibits a better anti-inflammatory effect than pure GL (63.4% inhibition vs 53.7% inhibition). The findings presented here suggested that GL-HP-ßCD NF could serve as a useful strategy for improving the therapeutic effects of GL.

Encapsulation and Biological Activity of Hesperetin Derivatives with HP-ß-CD.

The encapsulation of insoluble compounds can help improve their solubility and activity. The effects of cyclodextrin encapsulation on hesperetin's derivatives (HHSB, HIN, and HTSC) and the physicochemical properties of the formed complexes were determined using various analytical techniques. The antioxidant (DPPH•, ABTS•+ scavenging, and Fe2+-chelating ability), cytotoxic, and antibacterial activities were also investigated. The inclusion systems were prepared using mechanical and co-evaporation methods using a molar ratio compound: HP-ß-CD = 1:1. The identification of solid systems confirmed the formation of two inclusion complexes at hesperetin (CV) and HHSB (mech). The identification of systems of hesperetin and its derivatives with HP-ß-CD in solutions at pHs 3.6, 6.5, and 8.5 and at various temperatures (25, 37 and 60 °C) confirmed the effect of cyclodextrin on their solubility. In the DPPH• and ABTS•+ assay, pure compounds were characterized by higher antioxidant activity than the complexes. In the FRAP study, all hesperetin and HHSB complexes and HTSC-HP-ß-CD (mech) were characterized by higher values of antioxidant activity than pure compounds. The results obtained from cytotoxic activity tests show that for most of the systems tested, cytotoxicity increased with the concentration of the chemical, with the exception of HP-ß-CD. All systems inhibited Escherichia coli and Staphylococcus aureus.

Effect of Cyclodextrin Complex Formation on Solubility Changes of Each Drug Due to Intermolecular Interactions between Acidic NSAIDs and Basic H2 Blockers.

One of the solubilization of poorly water-soluble drugs is the use of cyclodextrin (CD)-based inclusion complexes. On the other hand, few studies have investigated how CD functions on the solubility of drugs in the presence of multiple drugs that interact with each other. In this study, we used indomethacin (IND) and diclofenac (DIC) as acidic drugs, famotidine (FAM) and cimetidine (CIM) as basic drugs, and imidazole (IMZ), histidine (HIS), and arginine (ARG) as compounds structurally similar to basic drugs. We attempted to clarify the effect of ß-CD on the solubility change of each drug in the presence of multiple drugs. IND and DIC formed a eutectic mixture in the presence of CIM, IMZ, and ARG, which greatly increased the intrinsic solubility of the drugs as well as their affinity for ß-CD. Furthermore, the addition of high concentrations of ß-CD to the DIC-FAM combination, which causes a decrease in solubility due to the interaction, improved the solubility of FAM, which was decreased in the presence of DIC. These results indicate that ß-CD synergistically improves the solubility of drugs in drug-drug combinations, where the solubility is improved, whereas it effectively improves the dissolution rate of drugs in situations where the solubility is reduced by drug-drug interactions, such as FAM-DIC. This indicates that ß-CD can be used to improve the physicochemical properties of drugs, even when they are administered in combination with drugs that interact with each other.