Preparation Of Inclusion Complexes Research Articles

The Antitumoral Effect In Ovo of a New Inclusion Complex from Dimethoxycurcumin with Magnesium and Beta-Cyclodextrin.

Breast cancer is one of the leading causes of death in the female population because of the resistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubility and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxycurcumin magnesium complex (DiMeOC-Mg, (4)) with beta-cyclodextrin (DiMeOC-Mg-BCD, (5)) in the stoichiometric relationship 1:1. This new inclusion complex's solubility in aqueous media phosphate buffer saline (PBS) was improved by a factor of 6x over the free metal complex (4). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3) expression levels on MD Anderson metastasis breast-231 cancer (MDA-MB-231) cell lines. Results of an antitumor assay in an in ovo model showed up to 30% inhibition of tumor growth for breast cancer (MDA-MB-231) when using (5) (0.650 mg/kg dose) and 17.29% inhibition with the free homoleptic metal complex (1.5 mg/kg dose, (4)). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new compound (5) exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.

Preparation of an inclusion complex of nickel-based β-cyclodextrin: Characterization and accelerating the osteoarthritis articular cartilage repair

Abstract Osteoarthritis is caused by the cartilage destruction of the bones of the joint surfaces and structures that produce synovium fluid. Osteoarthritis treatment includes the use of surgical methods and non-surgical or maintenance treatments including knee orthoses, medical insoles with external edges, use of physiotherapy techniques, exercise, weight loss in obese people, and teaching the principles of joint care. The main goal of treatment in osteoarthritis of the knee is to ameliorate physical function, decrease pain, and reduce the progression of the disease, through correcting the knee alignment and reducing the varus torque. Previous studies have indicated that medicinal plants and herbal nanoparticles (NPs) have the best anti-inflammatory effects. β-Cyclodextrin is a cyclic carbohydrate molecule that is used as a host to prepare inclusion complexes. In this study, the synthesis of nickel NPs is based on β-cyclodextrin (NiBCD NPs) for accelerating the osteoarthritis articular cartilage repair. The FT-IR and XRD techniques confirmed the formula of NiO for the NiBCD NPs. The FE-SEM imaging shows a non-spherical structure for NiBCD NPs with a size of less than 100 nm. In EDX, the signals at the energy levels of 8.3, 7.5, and 0.87 keV are assigned for the electron migration of Ni Kβ, Ni Kα, and Ni Lα. Furthermore, the signals for the elements of oxygen and carbon of BCD appeared at 0.52 and 0.28 keV. The effectiveness of NiBCD NPs in promoting chondrogenesis was examined in orthopedic experiments using primary cultured chondrocytes. Subsequently, we determined the functional restoration following NiBCD NPs’ transplantation in a knee osteoarthritis articular cartilage injury model. We conducted histological, PCR, and Western blot assays. In the immunological analysis, the levels of MMPs, IL-1β, TNF-α, and p-p65 expression were found to be reduced by NiBCD NPs. This reduction may be attributed to the regulation of cellular redox homeostasis through Nrf2. Furthermore, our findings demonstrated the positive impact of NiBCD NPs on stimulating chondrogenesis in vitro. Notably, the NiBCD NPs’ application accelerated the recovery of injury-induced dysfunction. Additionally, the presence of NiBCD NPs at the injury site suppressed abnormal fibrosis and angiogenesis. The histological assay revealed the chondrocytes’ proliferation and increased cartilage matrix synthesis in the NiBCD NPs’ presence.

Inclusion Complexes of Litsea cubeba (Lour.) Pers Essential Oil into β-Cyclodextrin: Preparation, Physicochemical Characterization, Cytotoxicity and Antifungal Activity.

The uses of natural compounds, such as essential oils (EOs), are limited due to their instability to light, oxygen and temperature, factors that affect their application. Therefore, improving stability becomes necessary. The objective of this study was to prepare inclusion complexes of Litsea cubeba essential oil (LCEO) with β-cyclodextrin (β-CD) using physical mixing (PM), kneading (KN) and co-precipitation (CP) methods and to evaluate the efficiency of the complexes and their physicochemical properties using ATR-FTIR, FT-Raman, DSC and TG. The study also assessed cytotoxicity against human colorectal and cervical cancer cells and antifungal activity against Aspergillus flavus and Fusarium verticillioides. The complexation efficiency results presented significant evidence of LCEO:β-CD inclusion complex formation, with KN (83%) and CP (73%) being the best methods used in this study. All tested LCEO:β-CD inclusion complexes exhibited toxicity to HT-29 cells. Although the cytotoxic effect was less pronounced in HeLa tumor cells, LCEO-KN was more active against Hela than non-tumor cells. LCEO-KN and LCEO-CP inclusion complexes were efficient against both toxigenic fungi, A. flavus and F. verticillioides. Therefore, the molecular inclusion of LCEO into β-CD was successful, as well as the preliminary biological results, evidencing that the β-CD inclusion process may be a viable alternative to facilitate and increase future applications of this EO as therapeutic medication, food additive and natural antifungal agent.

Characterization, Preparation, and Promotion of Plant Growth of 1,3-Diphenylurea/β-Cyclodextrin Derivatives Inclusion Complexes.

The study aimed to prepare inclusion complexes of 1,3-diphenylurea (DPU) with β-cyclodextrin (βCD) and 2-hydroxypropyl-β-cyclodextrin (HP-βCD) using a three-dimensional ground mixture (3DGM). Their physicochemical properties, intermolecular interactions, solubilities, and plant growth-promoting activities were investigated on broccoli sprouts. Phase-solubility diagrams indicated the stability constant (Ks) and complexation efficiency (CE) of βCD/DPU were found to be K1/1 = 250 M-1, CE = 2.48× 10-3. The Ks and CEs of HP-βCD/DPU were found to be K1/1 = 427 M-1, CE = 3.93 × 10-3 and K2/1 = 196 M-1, CE = 1.93 × 10-3 respectively. The powder X-ray diffraction results of 3DGM (βCD/DPU = 2/1, HP-βCD/DPU = 2/1) showed that the diffraction peaks originating from the DPU and βCD disappeared, indicating a halo pattern. Differential scanning calorimetry results showed an endothermic peak at 244 °C derived from the melting point of DPU, but the endothermic peak disappeared in the 3DGM (βCD/DPU = 2/1, HP-βCD/DPU = 2/1). Near-infrared absorption spectra showed peak shifts in 3DGM (βCD/DPU and HP-βCD/DPU) at the -CH and -NH groups of DPU and the -OH groups of βCDs and free water. In the dissolution test (after 5 min), the concentration of intact DPU was 0.083 μg/mL. However, the dissolution concentrations of DPU in the 3DGM (βCD/DPU = 1/1), 3DGM (βCD/DPU = 2/1), 3DGM (HP-βCD/DPU = 1/1), and 3DGM (HP-βCD/DPU = 2/1) were 3.27, 3.64, 5.70, and 7.03 μg/mL, respectively, indicating higher solubility than that of the intact DPU. Further, 1H-1H NOESY NMR spectroscopic measurements showed cross-peaks between H-A (7.32 ppm) and H-B (7.12 ppm) of DPU and H-6 (3.79 ppm) in the βCD cavity of the 3DGM (βCD/DPU = 2/1). A cross-peak was also observed among DPU H-A (7.32 ppm), H-B (7.11 ppm), and H-6 (3.78 ppm) in the βCD cavity. The results of the broccoli sprout cultivation experiment showed that 3DGM (βCD/DPU = 1/1), 3DGM (βCD/DPU = 2/1), 3DGM (HP-βCD/DPU = 1/1), and 3DGM (HP-βCD/DPU = 2/1) increased the stem thickness compared with that of the control group (DPU). These results indicated that the βCD/DPU and HP-βCD/DPU inclusion complexes were formed by the three-dimensional mixing and milling method, which enhanced the solubility and plant growth-promoting effects.

Formulation of multicomponent inclusion complex of cyclodextrin-amino acid with Chrysin: Physicochemical characterization, cell viability and apoptosis assessment in human primary glioblastoma cell line

Chrysin (CR) is a water-insoluble drug reported for different therapeutic effects. The microwave irradiation method was used in this study to create a multicomponent inclusion complex (CR-MC) containing CR (drug) and carrier hydroxyl propyl beta cyclodextrin (HP β CD) and L-arginine (LA). The prepared inclusion complex (CR-MC) was evaluated for dissolution study and results were compared with chrysin physical mixture (CR-PM). Further, the samples were assessed for infra-red (IR), nuclear magnetic resonance (NMR), differential scanning calorimeter (DSC), scanning electron microscope (SEM) and molecular docking. Finally, the cell viability, reactive oxygen species and flow cytometer studies were also assessed to check the potential of the prepared inclusion complex on the human primary glioblastoma cell line (U87-MG cell). The phase solubility findings revealed a stability constant (773 mol L−1) as well as a complexation efficiency of 0.027. The dissolution study displayed a significant increase in CR release from CR-MC (99.03 ± 0.39%) > CR-PM (70.58 ± 1.16%) > pure CR (35.29 ± 1.55%). NMR and IR spectral data revealed no interaction between CR and carriers. SEM and DSC study results revealed the conversion into amorphous form. The molecular docking results illustrated a high docking score, which supports the findings of complex formation. The cell viability, reactive oxygen species, and flow cytometry studies results showed enhanced activity from CR-MC against the tested human primary glioblastoma cell line. From the results it has been observed that chrysin solubility significantly increased after complexation and there in vitro activity also enhanced against cancer cell line.

Preparation of inclusion complex between ellagic acid and hydroxypropyl-β-cyclodextrin

In recent years, the research and discovery of antioxidants of natural origin, such as those found plants, have increased dramatically. Ellagic acid is a bioactive compound found in many fruits and vegetables, which carries many biological activities, such as antioxidant, anti-inflammatory, anti-cancer and antibacterial activities. However, the low solubility of ellagic acid in water decreases its practical application. In this study, a complex of ellagic acid with hydroxypropyl-cyclodextrin was synthesized in the water-ethanol solvent. The results showed that the solvent with a volume content of EtOH of 20% was the most suitable for complex formation, with complexation yield of 46%. The complex was characterized by FTIR, DSC methods. The infrared spectrum of the complex is similar to that of HP-β-CD, however, the intensity and position of some oscillations in the complex have changed significantly, compared to spectra of EA and HP-β-CD. The sharp adsorbance band at 3475 cm-1 of the O-H bond of EA was not observed in the spectrum of the complex, indicating that the O-H group participated in the bonding and covered by the hollow cavity of the HP-β-CD molecules. The DSC curve of the complex shows that the melting points of EA and HPβCD in the complex are declined in terms of temperature and intensity. This is evidence that there is a complex interaction between EA and HPβCD. The complexation improved the solubility and antioxidant activity of EA. Especifically, the solubility of EA was increased by 3.2 times compared to raw EA; EC50 value of EA was reduced from 5.3x10-5 to 4.9x10-5mol. L-1 after complexation.

Ellagic Acid Inclusion Complex-Loaded Hydrogels as an Efficient Controlled Release System: Design, Fabrication and In Vitro Evaluation.

Oxidants play a crucial role in the development of oxidative stress, which is linked to disease progression. Ellagic acid is an effective antioxidant with applications in the treatment and prevention of several diseases, since it neutralizes free radicals and reduces oxidative stress. However, it has limited application due to its poor solubility and oral bioavailability. Since ellagic acid is hydrophobic, it is difficult to load it directly into hydrogels for controlled release applications. Therefore, the purpose of this study was to first prepare inclusion complexes of ellagic acid (EA) with hydroxypropyl-β-cyclodextrin and then load them into carbopol-934-grafted-2-acrylamido-2-methyl-1-propane sulfonic acid (CP-g-AMPS) hydrogels for orally controlled drug delivery. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) were used to validate ellagic acid inclusion complexes and hydrogels. There was slightly higher swelling and drug release at pH 1.2 (42.20% and 92.13%) than at pH 7.4 (31.61% and 77.28%), respectively. Hydrogels had high porosity (88.90%) and biodegradation (9.2% per week in phosphate-buffered saline). Hydrogels were tested for their antioxidant properties in vitro against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Additionally, the antibacterial activity of hydrogels was demonstrated against Gram-positive bacterial strains (Staphylococcus aureus and Escherichia coli) and Gram-negative bacterial strains (Pseudomonas aeruginosa).

Preparation and characterization of inclusion complex of Myristica fragrans Houtt. (nutmeg) essential oil with 2-hydroxypropyl-β-cyclodextrin

Nutmeg essential oil (NEO) is a natural condimentwith versatile biological activities. However, the application of NEO in food has several limitations due to its poor stability and low aqueous solubility. To overcome the shortcomings, this paper focused on the preparation of the inclusion complex (IC) of NEO with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) by the coprecipitation method. The optimal condition was inclusion temperature 36 ℃, time 247 min, stirring speed 520 r/min, and wall-core ratio 12:1, resulting in a recovery of 80.63%. The formation of IC was verified by various methods such as scanning electron microscopy, Fourier transform infrared spectroscopy and nuclear magnetic resonance. The improvement of thermal stability, antioxidant, and nitrite scavenging activities of NEO after encapsulation was proven. Moreover, the controlled release of NEO from IC can be implemented by regulating the temperature and relative humidity. Overall, NEO/HP-β-CD IC has great application potential in food industries.

Synthesis and characterization of copolymers of β-cyclodextrin derivatives

Cyclodextrins (CDs) are cyclic oligosaccharides made up of d-glucose units connected by 1,4-glucosidic linkages. β-CD is a cyclical starch derivative containing seven glucopyranose units. β-CD derivatives have characteristic property of larger surface area, robust mechanical strength, high surface to volume ratio, electrical and optical properties for analyte determination, good dispersion, easy removal of the template, surface modification, functionalization and handling capacity. In this work, an attempt is made to prepare succinyl-β-CD-acrylamide (S-β-CD-AA) copolymer and β-CD-malic anhydride (β-CD-MAH) copolymer. For the synthesis of S-β-CD-AA, S-β-CD derivative is prepared and further, acrylamide (AA) along with cross-linker undergoes free radical copolymerization for the formation of gel like product. The degree of succinylation (DS) of β-CD derivative is estimated. S-β-CD-AA copolymer showed potential swelling, and deswelling characteristic. Another copolymer is prepared from β-CD malic anhydride derivative. Further, the derivative is treated with cellulose and ethylene diamine tetra acetate (EDTA) to form β-CD-MAH copolymer. The two derivatives are characterized by several techniques. Thermal stability of these copolymers is estimated with the help of thermogravimetric analysis. The basic characterization of the presence of functional groups is done using UV–visible spectroscopy, and infrared spectroscopy. The elemental analysis helped to estimate C, H, N, S in the synthesized compounds. The surface morphology characterization is done with the help of scanning electron microscopy. X-ray diffraction analysis helped in determination of crystal structure of β-CD-MAH. β-CD derivatives prepared may be potential candidate to prepare inclusion complex, in drug delivery, drug loading and several similar applications.

Evaluation on the inclusion behavior of β-cyclodextrins with lycorine and its hydrochloride

Lycorine (Lyc) and its hydrochloride (Lyc∙HCl) as effective drugs can fight against many diseases including novel coronavirus (COVID-19) based on their antiviral and antitumor mechanism. Beta-cyclodextrin (β-CD) is considered a promising carrier in improving its efficacy while minimizing cytotoxicity due to the good spatial compatibility with Lyc. However, the detailed mechanism of inclusion interaction still remains to be further evaluated. In this paper, six inclusion complexes based on β-CDs, Lyc and Lyc∙HCl were processed through ultrasound in the mixed solvent of ethanol and water, and their inclusion behavior was characterized after lyophilization. It was found that the inclusion complexes based on sulfobutyl-beta-cyclodextrin (SBE-β-CD) and Lyc∙HCl had the best encapsulation effect among prepared inclusion complexes, which may be attributed to the electrostatic interaction between sulfonic group of SBE-β-CD and quaternary amino group of Lyc∙HCl. Moreover, the complexes based on SBE-β-CD displayed pH-sensitive drug release property, good solubilization, stability and blood compatibility, indicating their potential as suitable drug carriers for Lyc and Lyc∙HCl.

Ιnclusion Complexes of Magnesium Phthalocyanine with Cyclodextrins as Potential Photosensitizing Agents.

In this work, the preparation of inclusion complexes, (ICs) using magnesium phthalocyanine (MgPc) and various cyclodextrins (β-CD, γ-CD, HP-β-CD, Me-β-CD), using the kneading method is presented. Dynamic light scattering (DLS) indicated that the particles in dispersion possessed mean size values between 564 to 748 nm. The structural characterization of the ICs by infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy provides evidence of the formation of the ICs. The release study of the MgPc from the different complexes was conducted at pH 7.4 and 37 °C, and indicated that a rapid release ("burst effect") of ~70% of the phthalocyanine occurred in the first 20 min. The kinetic model that best describes the release profile is the Korsmeyer-Peppas. The photodynamic therapy studies against the squamous carcinoma A431 cell line indicated a potent photosensitizing activity of MgPc (33% cell viability after irradiation for 3 min with 18 mW/cm2), while the ICs also presented significant activity. Among the different ICs, the γ-CD-MgPc IC exhibited the highest photokilling capacity under the same conditions (cell viability 26%). Finally, intracellular localization studies indicated the enhanced cellular uptake of MgPc after incubation of the cells with the γ-CD-MgPc complex for 4 h compared to MgPc in its free form.

Complexation between the Antioxidant Pterostilbene and Derivatized Cyclodextrins in the Solid State and in Aqueous Solution.

Inadequate aqueous solubilities of bioactive compounds hinder their ability to be developed for medicinal applications. The potent antioxidant pterostilbene (PTB) is a case in point. The aim of this study was to use a series of modified water-soluble cyclodextrins (CDs), namely, hydroxypropyl β-CD (HPβCD), dimethylated β-CD (DIMEB), randomly methylated β-CD (RAMEB), and sulfobutyl ether β-CD sodium salt (SBECD) to prepare inclusion complexes of PTB via various solid, semi-solid, and solution-based treatments. Putative CD-PTB products generated by solid-state co-grinding, kneading, irradiation with microwaves, and the evaporative treatment of CD-PTB solutions were considered to have potential for future applications. Primary analytical methods for examining CD-PTB products included differential scanning calorimetry and Fourier transform infrared spectroscopy to detect the occurrence of binary complex formation. Phase solubility analysis was used to probe CD-PTB complexation in an aqueous solution. Complexation was evident in both the solid-state and in solution. Complex association constants (K1:1) in an aqueous solution spanned the approximate range of 15,000 to 55,000 M-1; the values increased with the CDs in the order HPβCD < DIMEB < RAMEB < SBECD. Significant PTB solubility enhancement factors were recorded at 100 mM CD concentrations, the most accurately determined values being in the range 700-fold to 1250-fold.

Formulation of nitrendipine/hydroxypropyl-β-cyclodextrin inclusion complex as a drug delivery system to enhance the solubility and bioavailability by supercritical fluid technology

In this study, the solution enhanced dispersion by supercritical fluids (SEDS) technology was applied to prepare inclusion complex with hydroxypropyl-β-cyclodextrin (HP-β-CD) as carrier to enhance the oral bioavailability of nitrendipine (NT). The obtained particles were characterized by XRD, SEM, FT-IR, DSC, MS and NMR, which demonstrated the formation of inclusion complex in supercritical CO2. The phase solubility tests revealed that the complexation of NT with HP-β-CD was established in a 1:1 stoichiometry. The effects of different operating parameters, including the solvent, temperature, pressure, molar ratio, and concentration, on the particle size and dissolution were investigated in detail. The results proved that the SEDS technology markedly improved the solubility and dissolution of NT compared with pure NT and physical mixture. This study provides a theoretical basis for obtaining an inclusion complex with high solubility and low toxicity using SEDS technology.

Enhanced L-asparaginase stability through immobilization in supramolecular nanogels of PEG-grafted poly HPMA with bis(α-cyclodextrin)

This paper presents the fabrication of a biocompatible supramolecular nanogel containing immobilized L-asparaginase (ASNase), an anti-leukemic therapeutic agent, to improve the enzyme’s physicochemical stability. The ASNase-conjugated random copolymer of N-(2-Hydroxypropyl)methacrylamide (HPMA) and polyethylene glycol (PEG) acrylate was simply combined with inter-molecularly crosslinked α-cyclodextrin (bisCD) in physiologic condition to prepare inclusion complex nanogels. The introduction of bisCD led to the formation of discrete, homogenous, and spherical nanogels with a mean projected diameter of 148 nm for the best formulation of ASNase bioconjugate in terms of polymer succination ratio and polymer:protein ratio. The Michaelis-Menten constant (Km) for immobilized ASNase was 1.6-fold lower than the free form, indicating a higher affinity for the asparagine substrate. The ASNase immobilization significantly extended the pH stability range. In addition, when compared to the free enzyme, ASNase-bisCD nanogel exhibited superior stability against elevated temperature, freeze-thaw cycles, and proteolysis. Overall, the immobilization of ASNase in bisCD nanogels yields a novel stabilized preparation with promising biomedical applications.

Oral supplementation of solvent-free kynurenic acid/cyclodextrin nanosponges complexes increased its bioavailability

Many nutraceuticals present problems due to their poor water solubility or stability, which prevents the final bioactivity achievement. For that reason, the oral administration of KYNA complexed with HPβ-CD and βNS-CDI nanosponges was evaluated in mice. The solvent-free technology was used to prepare the complexes in a complete comparison between kneading in ball milling and classical inclusion complex preparation. The solvent-free ones showed higher strength and efficiency with ball milling, considerably reducing time. A 50 mg KYNA/kg/day dosage was orally administered in formulations showing a higher bioavailability when the nutraceutical was complexed with βNS-CDI compared to HPβ-CD and free KYNA, respectively. Several antioxidant statuses demonstrated a higher global antioxidant level perfectly related to bioavailability. Finally, the formulation of KYNA reduced the temporal oxidative stress damage in the kidney and liver, making βNS-CDI the best formulation. These results suggest an important future application of cyclodextrin-based nanosponges for the oral delivery of nutraceuticals and their stabilization.

Gliclazide in Binary and Ternary Systems Improves Physicochemical Properties, Bioactivity, and Antioxidant Activity

The poor solubility of the antidiabetic drug gliclazide (Glc) is due to its hydrophobic nature. This research is aimed at improving Glc's solubility and drug release profile, as well as at investigating additional benefits such as bioactivity and antioxidant activity, by forming binary complexes with HPβCD at different w/w ratios (1 : 1, 1 : 2.5, 1 : 4, and 1 : 9) and ternary complexes with HPβCD and Tryp at 1 : 1 : 1, 1 : 1 : 0.27, 1 : 2.5 : 0.27, 1 : 3.6 : 3.6, 1 : 4 : 1, and 1 : 9 : 1, respectively. Complexes were prepared by the physical mixing (PM) and solvent evaporation (SE) methods. The prepared inclusion complexes were meticulously characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectra. To verify our findings, the inclusion complexes were evaluated by equilibrium solubility, in vitro drug release profile, kinetic models, and antidiabetic and antioxidant activities in animal models. Our results demonstrated that the solubility and drug release profile were found to be enhanced through binary as well as ternary complexes. Notably, ternary complexes with a ratio of 1 : 9 : 1 showed the highest solubility and drug release profile compared to all other preparations. Data on antioxidant activity indicated that the ternary complex had the higher total antioxidant status (TAS), superoxide dismutase (SOD), and catalase (CAT) activity than the binary complex and Glc alone, in contrast to the diabetic group. In vivo antidiabetic activity data revealed a high percentage reduction in the blood glucose level by ternary complexes (49-52%) compared to the binary complexes (45-46%; p ≤ 0.05). HPβCD and Tryp provide a new platform for overcoming the challenges associated with poorly soluble Glc by providing greater complexing and solubilizing capabilities and imparting ancillary benefits to improve the drug's antidiabetic and antioxidant activities.

Encapsulation of Benzyl Isothiocyanate with β-Cyclodextrin Using Ultrasonication: Preparation, Characterization, and Antibacterial Assay.

Benzyl isothiocyanate (BITC) is widely utilized in multiple biomedical fields, due to its significant antibacterial properties and low toxicity. However, poor water solubility and pungent odor has limited its application in the food industry. In this study, we first prepared inclusion complexes of BITC in GLU-β-CD and HP-β-CD using ultrasound, which is able to overcome the hindrance of poor water solubility and high volatility. Then, the BITC-β-CD inclusion complexes were characterized by using high-performance liquid chromatography (HPLC), nuclear magnetic resonance hydrogen spectra (1H-NMR), infrared absorption spectra (IR), and differential scanning calorimetry (DSC) to confirm their stability. Further, the evaluation of antibacterial and antitumor effects of the BITC-β-CD inclusion complexes showed that they had great bactericidal activity against both Escherichia coli and Staphylococcus aureus cells, and also inhibited the growth of HepG2 cells in vitro. In addition, our results indicated that BITC-β-CD complexes were able to inhibit the growth of S. aureus in broccoli juice and extend the shelf life of broccoli juice, demonstrating the potential of β-cyclodextrin to improve the stability and controlled release of BITC. Taken together, our results show that BITC-β-CD complexes have good potential for application in the food industry.

Formulation and Evaluation of Rosuvastatin Calcium Immediate Release Tablets Using Beta Cyclodextrin

In order to treat Hyperlipidaemia, Rosuvastatin, a Dyslipidaemia drug, inhibits the HMG-CoA reductase enzyme. However, the calcium form of Rosuvastatin (RST) has low bioavailability, undesirable dissolving characteristics, and issues with absorption. Thus objective of the study is to increase the solubility and dissolution rate of Rosuvastatin calcium a poorly water-soluble 3-hydroxy 3-methyl glutaryl CoA (HMG-CoA) Reductase inhibitor through inclusion Complexation with β-cyclodextrin (β-CD). Therefore, the goal of the current study was to create a Rosuvastatin tablet formulation for oral dissolution. Rosuvastatin immediate tablets were developed using the direct compression showed good results, the prepared inclusion complex with β-CD by kneading method exhibited greatest enhancement in solubility and fastest dissolution (97.363) % RST release in 15 min. The inclusion complex contains RST: β-CD (1:1) and (1:2) was formulated into tablets using super disintegrants like Sodium starch glycolate, Cross povidone and Croscarmellose. All the mentioned batches were prepared and granules were evaluated for pre-compression parameters such as bulk density, tapped density and compressibility index. Tablets were evaluated for weight variation, thickness, hardness, friability; disintegration time and were found to be within the limits. In vitro dissolutions were carried out in 0.05M phosphate buffer with a pH of 6.8. The prepared tablet was evaluated for various post compression parameters like hardness, friability, weight variation, thickness, and in-vitro dissolution.

Hydroxypropyl-β-Cyclodextrin for Delivery of Sinapic Acid via Inclusion Complex Prepared by Solvent Evaporation Method

The goal of this study was to increase the aqueous solubility and dissolution rate of sinapic acid (SA) by formulating binary inclusion complex (BIC) of SA with hydroxypropyl-β-cyclodextrin (HPβCD) using solvent evaporation (SE) technology. The phase solubility and dissolution studies were conducted to determine the solubility and in vitro release rate of SA. In addition, the prepared inclusion complex was characterized for solid state characterization using techniques such as DSC, PXRD, SEM, and FTIR. Moreover, the prepared SA-BIC was evaluated for its antioxidant activity. Results revealed that the SA solubility can be shown to improve with a change in HPβCD concentration. About 2.59 times higher solubility of SA in water was noticed in the presence of HPβCD (10 mM). Dissolution study demonstrated that the 34.11 ± 4.51% of SA was released from binary physical mixture (BPM), while the maximum release of 46.27 ± 2.79% of SA was observed for SA-BIC prepared by SE method. The prepared SA-BIC demonstrated distinctive properties when compared to pure SA, which was demonstrated by different analytical methods, such as DSC, PXRD, SEM, and FTIR, as evidence of SA inclusion into HPβCD cavity. Further, it was observed that SA-BIC displayed stronger DPPH radical scavenging activity than SA. In conclusion, SE technology considerably enhanced the complexity of SA with HPβCD, and these observations could help to heighten the SA solubility, which may lead to a better bioavailability.

Preparation, characterization, and antifungal property of the inclusion complex of Litsea cubeba essential oil/hydroxypropyl-β-cyclodextrin and its application in preservation of Shatang mandarin.

To explore the potential application of plant essential oil in the postharvest preservation of fruits, the inclusion complex (IC) of Litsea cubeba essential oil (LCEO) with hydroxypropyl-β-cyclodextrin (HPβCD), prepared by the saturated aqueous solution method, was studied. LCEO/HPβCD-IC was characterized by fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), particle size distribution, and thermogravimetric-differential scanning calorimetry (TG-DSC) analysis. The formation of LCEO/HPβCD-IC was confirmed, and the volume average particle diameter was 24.376µm. Due to the inclusion of HPβCD, the volatility of LCEO was significantly reduced and the thermal stability was significantly improved. In addition, the antifungal activities of the LCEO ICs were compared, and LCEO/HPβCD-IC was more effective against the citrus postharvest pathogens (P. italicum and G. citri-aurantii). The effects of the LCEO ICs on the postharvest quality of Shatang mandarin were studied. Compared with the control group (CK) and LCEO/βCD-IC group, the LCEO/HPβCD-IC group showed a significant delay in the decrease of good fruit rate, hardness, total soluble solids (TSSs), and Vitamin C (Vc) content, with a lower weight loss rate of Shatang mandarin. Therefore, LCEO/HPβCD-IC is expected to be used as a green preservative for the storage and preservation of citrus fruits. PRACTICAL APPLICATION: In this study, LCEO was encapsulated in HPβCD by the saturated aqueous solution method and the prepared inclusion complex was characterized. The effects of LCEO/HPβCD-IC and LCEO/βCD-IC on postharvest preservation of Shatang mandarin were compared. This work offers valuable insights into the postharvest preservation of citrus fruit by essential oil inclusion complexes.