Β-cyclodextrin Complexes Research Articles

The mechanochemical and supercritical fluid synthesis of β-cyclodextrin-hesperidin inclusion complex: A comparison green chemistry versus lyophilization

Hesperidin is a rutinoside of flavanone type with relevant therapeutic properties but poor water solubility which limits its therapeutic applicability. However, cyclodextrins (CDs) have been successfully used as drug carriers to enhance the solubility of several drugs, to improve their bioavailability, and therapeutic efficacy. We report herein the formation of inclusion complexes of β-cyclodextrin and hesperidin through the green approaches mechanochemistry and supercritical fluid and compare these results versus the classical lyophilization method. The resulting stoichiometries and the specific interactions of the complexes were analyzed by NMR, UV, and mass spectrometry. The β-cyclodextrin and hesperidin inclusion complex (IC) successfully obtained through green methodologies demonstrated superior levels of flavonoid content. In terms of solubility, the mechanochemistry inclusion complex showed the best improvement in solubility. We demonstrate herein that the use of green methodologies such as supercritical fluids and mechanochemistry are useful alternatives to the conventional method of lyophilization, to improve the solubility of β-cyclodextrin IC.

Alginate-based edible coating with magnoliae essential oil/β-cyclodextrin inclusion complex for Kyoho grape preservation

To prolong the shelf life of Kyoho grapes at room temperature, an edible coating composed of sodium alginate (SA) containing an inclusion complex of Magnoliae essential oil (MEO) and β-cyclodextrin (β-CD) (SA/MEO@β-CD coating) was developed. Initially, the inclusion complex of MEO with β-CD was developed to enhance its thermal stability. MEO@β-CD was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). In addition, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) results show that β-CD can improve the thermal stability of MEO. The entrapment efficiency and loading efficiency were 82.56% and 8.8%. MEO@β-CD was added to the SA coating for preserving Kyoho grapes, while monitoring the enzyme activity, total bacterial count, and sensory characteristics of the grapes. Compared to the uncoated group, the SA/MEO@β-CD coated group exhibited a significant reduction in total color difference, decay rate, weight loss rate, enzyme activity, and total number of bacterial colonies, while also slowing the decline in hardness and total soluble solids. The effect of the SA/MEO@β-CD1 group was highly effective. Conclusively, the SA/MEO@β-CD coating preserves Kyoho grapes by reducing lipid oxidation and inhibiting microbial growth, demonstrating its potential as an advanced edible packaging solution for grape preservation.

Development and Assessment of Loratadine Fast-Disintegrating Tablets via β-Cyclodextrin Complexation with Superdisintegrants

ABSTRACT: This study aimed to enhance the solubility and consequent bioavailability of Loratadine, a widely used medication for seasonal allergic rhinitis and chronic idiopathic urticaria. The approach involved complexation with β-cyclodextrin to improve solubility and the formulation of fast-disintegrating tablets via the sublimation method. Crosspovidone acted as a superdisintegrant, while camphor served as a sublimating agent. Methodology: Pre-compression parameters were assessed to ensure adequate flow properties, while post-compression parameters were evaluated against IP acceptable limits for variations in hardness, weight, wetting time, friability, drug release, and disintegration time, drug content, FTIR, and DSC. Dissolution studies were conducted in 0.1N HCL, and statistical analysis employed a central composite design for optimization. Results: Formulation B14 emerged as the optimized batch, demonstrating favourable characteristics including wetting time, in vitro drug release, drug content, and disintegration time. Analysis of stability conducted in accordance with ICH guidelines affirmed the formulations' stability. Conclusion: The developed fast-disintegrating tablet formulation of Loratadine exhibited enhanced solubility, potentially translating to improved bioavailability. These advancements suggest increase efficacy and improved patient compliance in the management of allergic rhinitis and urticaria.

Preparation of trimethoprim/methyl β-cyclodextrin complexes, in vitro and in vivo pharmacokinetic study, and evaluation of antibacterial activity in combination with the complex of sulfamethoxazole/methyl β-cyclodextrin

Through cyclodextrin selection from phase solubility study, complexation method screening, and complexation condition optimization by using single and orthogonal strategy, the complexes of trimethoprim with methyl β-cyclodextrin, HP β-cyclodextrin and HP-γ-cyclodextrin with the best solubility increasing so far were prepared and confirmed by FTIR, DSC and proton NMR spectra. The in vitro pharmacokinetic study showed that trimethoprim was 80 %–90 % released in three complexes in 20 min., and in their dog's in vivo pharmacokinetic study, the Cmax was increased from 0.22 µg/mL to 0.85 µg/mL, 0.7 µg/mL and 0.72 µg/mL, the AUC0∼40 was increased from 2.35 µg*h/mL to 3.94 µg*h/mL, 5.06 µg*h/mL and 6.73 µg*h/mL, the LC was shorten from 2.17 L/kg/h to 0.89 L/kg/h, 0.56 L/kg/h and 1.07 L/kg/h for the complexes with methyl β-cyclodextrin, HP β-cyclodextrin and HP-γ-cyclodextrin respectively. After combination with sulfamethoxazole cyclodextrin complex, the antibacterial activity of the complex of trimethoprim with methyl β-cyclodextrin was increased significantly compared with the pure drug alone, indicated that this complex can be used as new potent antibacterial agent.

Colloidal nanoparticles of a β-cyclodextrin/L-Tryptophan inclusion complex for use as Pickering emulsion stabilizers

Inclusion complexes of β-cyclodextrin (β-CD) and tryptophan (Trp) were synthesized using an antisolvent approach, and fully characterized. Scanning electron microscope images proved the formation of the β-CD/Trp nanoparticles (NP) and the powder X-ray diffraction pattern indicated the formation of a crystalline channel-like structure for the β-CD/Trp NPs (NPs). The NPs of a β-CD/Trp inclusion complex were used as a natural stabilizer at the oil/water interface of a Pickering emulsion. Pickering emulsions with an oil to water ratio of 1:1 (v:v) were obtained under high-speed homogenization and different mass ratios of the β-CD to Trp (1:0, 1:0.1, 1:0.25, 1:0.5, 1:1), and at different pH levels (3, 5, 7, 9). At pH 9, when the β-CD:Trp mass ratio was 1:0.1, the β-CD/Trp NPs were hydrophilic, and the oil-in-water Pickering emulsions stabilized by those nanoparticles showed the highest storage stability: 180 days at room temperature. In contrast, when the emulsions were prepared at pH 5 with the weight ratios of either 1:0.1 or 1:1, β-CD:Trp, the nanoparticles were hydrophobic and could be used to stabilize water-in-oil Pickering emulsions.

Photochromism, Thermochromism, and Electrochromism in Solid-State Host-Guest Inclusion Complexes of β-Cyclodextrin with Dialkylcarboxyl-Substituted Viologens.

Multi-stimuli-responsive chromic materials have immense potential for utilization. Herein, two supramolecular inclusion complexes were prepared by self-assembly of β-cyclodextrin (β-CD) with dialkylcarboxyl-substituted viologens, N,N'-di(3-carboxy-propyl)-4,4'-bipyridinium dichloride (CPV·Cl2) and N,N'-di(6-carboxy-hexyl)-4,4'-bipyridinium dibromide (CHV·Br2). The self-assembled inclusion complexes CPV2+@β-CD and CHV2+@β-CD2 in the solid-state exhibited naked-eye photochromism, thermochromism, and electrochromism in response to multiple external stimuli including light, temperature, and electric field, respectively. Solid-state UV-vis diffuse reflectance and electron spin resonance (ESR) spectroscopy revealed that the observed photochromism, thermochromism and electrochromism are attributed to the formation of viologen free radicals induced by electron transfer under external stimuli. The excellent stimuli-response chromic properties of the title inclusion complexes support their practical utility in visual display, multiple anticounterfeiting, and multilevel information encryption.

Development of itraconazole ocular delivery system using β-cyclodextrin complexation incorporated into dissolving microneedles for potential improvement treatment of fungal keratitis

Itraconazole (ITZ) is one of the broad-spectrum antifungal agents for treating fungal keratitis. In clinical use, ITZ has problems related to its poor solubility in water, which results in low bioavailability when administered orally. To resolve the issue, we formulated ITZ into the inclusion complex (ITZ-IC) system using β-cyclodextrin (β-CD), which can potentially increase the solubility and bioavailability of ITZ. The molecular docking study has confirmed that the binding energy of ITZ with the β-CD was −5.0 kcal/mol, indicating a stable conformation of the prepared inclusion complex. Moreover, this system demonstrated that the inclusion complex could significantly increase the solubility of ITZ up to 4-fold compared to the pure drug. Furthermore, an ocular drug delivery system was developed through dissolving microneedle (DMN) using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) as polymeric substances. The evaluation results of DMN inclusion complexes (ITZ-IC-DMN) showed excellent mechanical strength and insertion ability. In addition, ITZ-IC-DMN can dissolve rapidly upon application. The ex vivo permeation study revealed that 75.71% (equivalent to 3.79 ± 0.21 mg) of ITZ was permeated through the porcine cornea after 24 h. Essentially, ITZ-IC-DMN exhibited no signs of irritation in the HET-CAM study, indicating its safety for application. In conclusion, this study has successfully developed an inclusion complex formulation containing ITZ using β-CD in the DMN system. This approach holds promise for enhancing the solubility and bioavailability of ITZ through ocular administration.

7-Phenylheptanoic Acid-Hydroxypropyl β-Cyclodextrin Complex Slows the Progression of Renal Failure in Adenine-Induced Chronic Kidney Disease Mice.

The characteristic accumulation of circulating uremic toxins, such as indoxyl sulfate (IS), in chronic kidney disease (CKD) further exacerbates the disease progression. The gut microbiota, particularly gut bacterial-specific enzymes, represents a selective and attractive target for suppressing uremic toxin production and slowing the progression of renal failure. This study investigates the role of 4-phenylbutyrate (PB) and structurally related compounds, which are speculated to possess renoprotective properties in suppressing IS production and slowing or reversing renal failure in CKD. In vitro enzyme kinetic studies showed that 7-phenylheptanoic acid (PH), a PB homologue, suppresses the tryptophan indole lyase (TIL)-catalyzed decomposition of tryptophan to indole, the precursor of IS. A hydroxypropyl β-cyclodextrin (HPβCD) inclusion complex formulation of PH was prepared to enhance its biopharmaceutical properties and to facilitate in vivo evaluation. Prophylactic oral administration of the PH-HPβCD complex formulation reduced circulating IS and attenuated the deterioration of renal function and tubulointerstitial fibrosis in adenine-induced CKD mice. Additionally, treatment of moderately advanced adenine-induced CKD mice with the formulation ameliorated renal failure, although tissue fibrosis was not improved. These findings suggest that PH-HPβCD can slow the progression of renal failure and may have implications for preventing or managing CKD, particularly in early-stage disease.

Inclusion complex of 2-phenylethanol in β-cyclodextrin: Preparation, characterization, computational study and evaluation of antinociceptive activity

In the present research, we employed advanced technologies, developing new investigations aiming to obtain simple and inexpensive molecules to reduce pain sensation. For the first time, the inclusion complex of 2-phenylethanol (2-PE) and β-cyclodextrin (β-CD) was achieved (using a spray drying) and characterized using spectroscopic, thermal, and computational methods. Additionally, the system was evaluated for its antinociceptive abilities. Evidence of inclusion complex formation was provided based on various techniques, such as X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR), and then deduced by pharmacological experiments, which showed significant changes compared to the initial components.

Formation of Inclusion Complexes of 2-Hydroxypropyl β-Cyclodextrin with 2-Hydroxychalcone: Experimental and Theoretical Study

The formation of inclusion complexes of 2-hydroxypropyl-β-cyclodextrin (HP β-CD) with 2-hydroxychalcone (2HOCH) in solution and solid state was investigated using UV–Visible, fluorescence, Fourier transform-infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscope (SEM) techniques. The results obtained confirmed that 2HOCH formed the stable inclusion complex with HP β-CD. Moreover, the spectral data and Benesi–Hildebrand plots results indicated that the stoichiometry of the inclusion complex was 1:1. Theoretically, the structure of the inclusion complexes and the physical parameters such as complexation energy, highest occupied molecular orbital–lowest unoccupied molecular orbital, and energy gap were obtained using the DFT/B3LYP/6-311G method. It was found that the complexation energy for orientation B was lower than that for orientation A as evidenced by the theoretical calculations. Moreover, the carbonyl group of molecules was located outside of the cyclodextrin cavity while the hydroxyl group was located inside the cavity. The antioxidant capacity and antibacterial responses of the inclusion complexes and, for comparison, the parent compounds were also carried out.

Quality by Design Enabled β-Cyclodextrin Complexes of Lisinopril by Kneading Method: Improved Solubility and Bioavailability

Background: The primary intent of the study is to formulate the inclusion complex of lisinopril with the varied compositions of polymers like β-cyclodextrin for the enhancement of oral drug solubility and bioavailability using QbD approach. Methods: The application of Box-behnken design to determine the optimized run from the prepared inclusion complexes. The physical kneading technique with β-cyclodextrin at varied amounts was used to create the inclusion complex of lisinopril. Results: The FT-IR analysis study confirmed the selected drug, polymers, and other excipients showed no physical interactions. The prepared inclusion complexes' particle sizes and encapsulation efficiency were between 802 to 3259μm, 19.22 to 93.28%. The optimized formulation batch (F5) showed 90.16% in vitro drug release at 24h compared to the pure drug. From the in vivo study, the pharmacokinetic parameters for the optimized formulation (F5) were found to be Cmax of 94.336 ng/ml, Tmax of 12h, and AUC 94.336 ng.h/ml, Kel of 0.0395h-1 and t1/2 of 12h. After three months, stability studies for the optimized formulation batch indicate no change in drug entrapment efficiency and other parameters. Conclusion: The β-cyclodextrin inclusion complex of lisinopril exhibited a 2-fold increase in the oral bioavailability of the model drug, which will be the novel drug-delivery strategy for the treatment of hypertension.

17-β-Estradiol—β-Cyclodextrin complex as an aqueous solution: Structural and physicochemical characterization supported by MM and QM calculations

17-β-estradiol (EST) is an Active Pharmaceutical Ingredient characterized by a low water solubility. Complexation with β-cyclodextrin (βCD) enhances its bioavailability, hence such complex is an interesting research object from pharmaceutical point of view. However, basic facts like description of complex's structure and definition of its molar ratio, were debatable already for decades. This work for the first time justifies the EST:βCD molar ratio as 1:2 using the HRMS (high-resolution mass spectrometry) and phase solubility studies. The latter are used to define complex stability constant, as well. The structure and stability is analyzed using a variety of computational approaches: Quantum Mechanics (QM) based methods (DFT, semiempirical approaches) and MD/MMGBSA approach. In case of the QM, for the first time in the computational analysis of cyclodextrin complexes, a thorough benchmarking test is presented. Different computational parameters (solvent model, presence/absence of dispersion correction etc.) are used. Obtained results are compared with the experimental data.

Preparation and characterization of ternary polysaccharide hydrogels based on carboxymethyl cellulose, carboxymethyl chitosan, and carboxymethyl β-cyclodextrin

A series of ternary polysaccharide hydrogels were facile prepared by incorporating carboxymethyl cellulose (CMC) into the carboxymethyl chitosan/carboxymethyl β-cyclodextrin (CMCS/CMCD) complex solution based on multiple physical interactions. Structure properties of the CMC/CMCS/CMCD hydrogels were revealed by FTIR, XRD, SEM, and TG. The rheological and texture properties, temperature/pH-response behaviors, biocompatablity, and antimicrobial activity of the hydrogels were determined in detail. These results showed that the existence of electron force and hydrogen bond among three components leading to formation of the hydrogels, displaying good mechanical characteristic, stable solid-like rheological properties, controllable swelling and degradation behaviors, and excellent biocompatibility. Additionally, the swelling kinetics can be well described by the Schott's pseudo second order model. Moreover, the hydrogels loaded with cinnamic acid (CA) exhibited good antimicrobial activity against both Staphylococcus aureus and Escherichia coli, and the antimicrobial activity was related to the composition of the prepared hydrogels. The novel ternary polysaccharide hydrogels may have good application prospects in food and bio-medicine.

Solid Forms and β-Cyclodextrin Complexation of Oxymetholone and Crystal Structure of Metribolone

Solid Forms and β-Cyclodextrin Complexation of Oxymetholone and Crystal Structure of Metribolone

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.

Investigation of Optimum Production Conditions and the Stability of β-Cyclodextrin-Perfluorocarbon Nanocone Clusters for Histotripsy Applications.

Nanocone clusters (NCCs) have been developed as clusters with inclusion complexes of FDA-approved β-cyclodextrin (βCD) and perfluorocarbons (PFC) (i.e., perfluoropentane (PFP) and perfluorohexane (PFH)) and have shown promise in nanoparticle-mediated histotripsy (NMH) applications owing to their lowered cavitation threshold, ease of production, and fluorocarbon quantification. However, there is still a lack of information on the best conditions of the synthesis of NCCs as a product that can have a maximum determinable fluorocarbon content and maintain the stability of the NCC during synthesis and when used as histotripsy agents or exposed to physiological conditions. These concerns about the stability of the clusters and the best possible formulation are investigated in the current work. The cluster formation potential was tested taking into consideration the nature of both PFCs and βCD by employing different synthesis conditions in terms of solution and environmental parameters such as concentration of solvent, stoichiometry between βCD and PFCs, temperature, pH, solvent type, etc. The best route of synthesis was then translated into various batch sizes and investigated in terms of the PFC loading and yield. These studies revealed that preparing NCCs in double-distilled water in an ice bath at the optimized solution concentration gave the highest yields and optimal PFC loading, as determined from gas chromatography. Furthermore, the stability of the clusters with different stoichiometries was scrutinized in varying concentrations, mechanical disruption times, pH levels, and temperature conditions, showing effects on each cluster's particle size in dynamic light scattering, visualized in transmission electron microscopy, and cavitation behavior in agarose gel tissue phantoms. These studies revealed stable clusters for all formulations, with PFH-containing NCCs emerging to be the most stable in terms of their cluster size and bubble formation potential in histotripsy. Finally, the shelf life of these clusters was investigated using DLS, which revealed a stable cluster. In conclusion, NCCs have shown high stability in terms of both synthesis, which can be replicated in gram-level production, and the cluster itself, which can be exposed to harsher conditions and still form stable bubbles in histotripsy.

Combining BNCT with carbonic anhydrase inhibition for mesothelioma treatment: Synthesis, in vitro, in vivo studies of ureidosulfamido carboranes

Mesothelioma is a malignant neoplasm of mesothelial cells caused by exposure to asbestos. The average survival time after diagnosis is usually nine/twelve months. A multi-therapeutic approach is therefore required to treat and prevent recurrence. Boronated derivatives containing a carborane cage, a sulfamido group and an ureido functionality (CA-USF) have been designed, synthesised and tested, in order to couple Boron Neutron Capture Therapy (BNCT) and the inhibition of Carbonic Anhydrases (CAs), which are overexpressed in many tumours. In vitro studies showed greater inhibition than the reference drug acetazolamide (AZ). To increase solubility in aqueous media, CA-USFs were used as inclusion complexes of hydroxypropyl β-cyclodextrin (HP-β-CD) in all the inhibition and cell experiments. BNCT experiments carried out on AB22 (murine mesothelioma) cell lines showed a marked inhibition of cell proliferation by CA-USFs, and in one case a complete inhibition of proliferation twenty days after neutron irradiation. Finally, in vivo neutron irradiation experiments on a mouse model of mesothelioma demonstrated the efficiency of combining CA IX inhibition and BNCT treatment. Indeed, a greater reduction in tumour mass was observed in treated mice compared to untreated mice, with a significant higher effect when combined with BNCT. For in vivo experiments CA-USFs were administered as inclusion complexes of higher molecular weight β-CD polymers thus increasing the selective extravasation into tumour tissue and reducing clearance. In this way, boron uptake was maximised and CA-USFs demonstrated to be in vivo well tolerated at a therapeutic dose. The therapeutic strategy herein described could be expanded to other cancers with increased CA IX activity, such as melanoma, glioma, and breast cancer.

Customizable orodispersible films: Inkjet printing and data matrix encoding for personalized hydrocortisone dosing

The aim of this study was to exploit the versatility of inkjet printing to develop flexible doses of drug-loaded orodispersible films that encoded information in a data matrix pattern, and to introduce a specialised data matrix-generator software specifically focused on the healthcare sector. Pharma-inks (drug-loaded inks) containing hydrocortisone (HC) were developed and characterised based on their rheological properties and drug content. Different strategies were investigated to improve HC solubility: formation of β-cyclodextrin complexes, Soluplus® based micelles, and the use of co-solvent systems. The software automatically adapted the data matrix size and identified the number of layers for printing. HC content deposited in each film layer was measured, and it was found that the proportion of co-solvent used directly affected the drug solubility and simultaneously played a role in the modification of the viscosity and surface tension of the inks. The formation of β-cyclodextrin complexes improved the drug quantity deposited in each layer. On the contrary, micelle-based inks were not suitable for printing. Orodispersible films containing flexible and low doses of personalised HC were successfully prepared, and the development of a code generator software oriented to medical use provided an additional, innovative, and revolutionary advantage to personalised medicine safety and accessibility.

Synthesis, characterization, and antioxidant efficiency of CoCu/(βCDhis) complex

This report describes the synthesis of a bimetallic cobalt-copper complex of histidine-containing β-cyclodextrin (βCDhis) capable of efficiently scavenging superoxide radicals and peroxide anions. A blue-violet CoCu/(βCDhis) complex was prepared in mole ratios of 0.165:0.25:1:1 of Co:Cu:his:βCD in water and characterized using UV–vis, TGA-DTA, EDX, powder XRD and FT-IR analytical techniques. TGA analysis and XRD patterns showed that histidine was incorporated within the β-cyclodextrin ring. UV–Vis and FT-IR spectroscopy confirmed that the histidine CO group interacts with copper and cobalt metals. The results of antioxidant activity tests showed that CoCu/(βCDhis) complex has the highest catalase (88 %), and peroxidase activity (87 %) per 0.005 g of the complex. The imidazole group in histidine increases the solubility of the synthesized complexes and the ability to scavenge hydroxyl radicals, therefore histidine enhances their antioxidant potential.

Comparative Analysis of the Structure and Pharmacological Properties of Some Piperidines and Host-Guest Complexes of β-Cyclodextrin.

Pain and anesthesia are a problem for all physicians. Scientists from different countries are constantly searching for new anesthetic agents and methods of general anesthesia. In anesthesiology, the role and importance of local anesthesia always remain topical. In the present work, a comparative analysis of the results of pharmacological studies on models of the conduction and terminal anesthesia, as well as acute toxicity studies of the inclusion complex of 1-methyl-4-ethynyl-4-hydroxypiperidine (MEP) with β-cyclodextrin, was carried out. A virtual screening and comparative analysis of pharmacological activity were also performed on a number of the prepared piperidine derivatives and their host-guest complexes of β-cyclodextrin to identify the structure-activity relationship. Various programs were used to study biological activity in silico. For comparative analysis of chemical and pharmacological properties, data from previous works were used. For some piperidine derivatives, new dosage forms were prepared as beta-cyclodextrin host-guest complexes. Some compounds were recognized as promising local anesthetics. Pharmacological studies have shown that KFCD-7 is more active than reference drugs in terms of local anesthetic activity and acute toxicity but is less active than host-guest complexes, based on other piperidines. This fact is in good agreement with the predicted results of biological activity.