Anti-inflammatory potential of orally administrated bioflavonoid-robinin, active sub-stance of original drug Flaroninum™ (FL), was investigated in the combination with methotrexate (MTX) and in monotherapy in rats suffering from adjuvant-induced arthritis (AA). Robinin (kaempferol-3-O-robinoside-7-O-rhamnoside) was isolated from the aerial parts of Astragalus falcatus Lam. The monotherapy with robinin was not efficient in alleviating symptoms of AA. The combination of MTX with robinin was similarly active as MTX alone in reducing the hind paw volume and change of body weight during the whole experiment. The combination, however, reduced plasma levels of Interleukin-17Aand activity of gamma-glutamyl transferase in joint more efficiently then MTX alone. Our results demonstrate that the novel combination of robinin and MTX mildly improved the reduction of inflammation in experimental arthritis.

Bentonite clays are broadly employed in the design of varied drug delivery systems due to their characteristic feature such as adsorption, swelling ability and biocompatibility. Combination polymers with clay particles considerably improve mechanical and physical properties, drug - encapsulation efficiency and controlled release behavior of hybrids comparing with the starting components. One of the priority research areas at the I. Kutateladze Institute of Pharmacochemistry is extension the usage potential of Georgian bentonite clay in pharmacy, medicine, veterinary and cosmetics. Numerous semisolid dosage forms and dry ointments were proposed by the Institute on the bases of preparation Tikha Ascane, obtained from the clay of Askana Deposit (Ozurgeti region of Georgia). The aim of this study was to examine the suitability of Tikha Ascane as a substrate for the obtaining hybrid material with Sodium alginate (SA) and develop and characterize drug loaded clay/ polymer hydrogel. Optimized formulation for Tikha Ascane/SA hybrids was selected and Nitrofurazone (NFZ) as a model drug was incorporated. The samples were characterized by examining FTIR spectra, morphology, viscosity, pH, homogeneity and appearance. Content of NFZ in hydrogel was determined by HPLC. FTIR analysis revealed that Tikha Ascane and SA act as a simply physical mixture. Infrared spectra showed that NFZ did not bind strongly to the hybrid material. Microscopic analyses allowed verification of homogeneity of samples. Optimal clay / polymer composites contained Tikha Ascane - SA at the ration of 1:3 (w/w) and 0.2 % w/w incorporated NFZ. From this work it is cleared that Georgian bentonite clay preparation - Tikha Ascane can be successfully used as a substrate for clay / polymer hybrid material; formulated complex exhibits promising characteristics that allows considering it as a potential drug delivery system. Further studies are on-going for the preparation of TA hybrid material with different polymers. ბენტონიტური თიხები ფართოდ გამოიყენება წამლის მიწოდების სისტემების დიზაინში მათთვის დამახასიათებელი ისეთი უნიკალური თვისებების გამო, როგორიცაა ადსორბირებისა და გაჯირჯვების უნარი, ბიოთავსებადობა. პოლიმერების კომბინაცია თიხის ნაწილაკებთან საგრძნობლად აუმჯობესებს მათ მექანიკურ და ფიზიკურ თვისებებს, წამლის ინკაფსულაციის ხარისხს და კონტროლირებადი გამოთავისუფლების უნარს. ი. ქუთათელაძის ფარმაკოქიმიის ინსტიტუტის კვლევის ერთ-ერთი პრიორიტეტული მიმართულებაა ქართული ბენტონიტური თიხის გამოყენების პოტენციალის გაფართოება ფარმაციაში, მედიცინაში, ვეტერინარიასა და კოსმეტოლოგიაში. ასკანას საბადოს თიხისგან (ოზურგეთის რაიონი, საქართველო) მიღებულ...

Vinca alkaloids are used extensively in the treatment of various diseases and despite their usefulness, drug resistance, attributed to a number of mechanisms associated with the multidrug-resistance phenotype including overexpression of P-glycoprotein (P-gp), remains a serious clinical problem. To identify the possible role of P-gp on the intestinal permeability of anti-arrhythmic crude alkaloids (Vingerbine) from Vinca herbaceae, Caco-2 cells were used in this study. The four Vingerbine constituent alkaloids were analyzed by high performance liquid chromatography (HPLC). Transport parameters, permeability coefficients and percent transports were calculated. Vingerbine constituent alkaloids displayed the identical tendency but with dissimilar degree of modulation in absorptive transport direction. Vincarine and Herbadine demonstrated higher-level intestinal transcellular efflux; the co-presence of verapamil, the absorptive transport of alkaloids increased, while the secretory decreased. No asymmetric permeation was observed for Herbamine and Vincamajine. The study suggests the involvement for multidrug resistance-associated proteins (MRPs) in the intestinal transcellular efflux of Vincarine and Herbadine. The further studies will be focused upon the screening appropriate nanomedicine-based strategies to combat MDR and thus improve intestinal absorption of anti-arrhythmic alkaloids.

Present study investigated the possible role of P-glycoprotein in the intracellular exposure of active substance (robinin) of natural medicine Flaroninum™ and effect of robinin on the cellular accumulation of mitoxantrone in either BCRP-overexpressing and BCRP-negative cells. Robinin - kaempferol-3-O-b-D-robinoside-7-O-α-L-rhamnopyranoside, has been obtained from over ground parts of Astragalus falcatus Lam., growing in Georgia. The compound possesses hypoazotemic and diuretic activities and is proposed for the complex therapy of kidney diseases. P-gp-overexpressing and P-gp-negative human breast cancer cells (MCF7) were used to examine the absorption character of kaempferol and robinin with or without of verapamil (P-gp inhibitor). Flavonoids concentrations were determined by LC/MS/MS. Robinin transport was P-gp-dependent and verapamil significantly increased the extent of uptake of robinin in cells, which is attributed in part to P-gp-inhibition by verapamil. When comparing the intracellular accumulation of aglycone with kaempferol-3-O-b-D-robinoside-7-O-α-L-rhamnopyranoside, we found that kaempferol uptake was greater than robinin. Since some glycosylated forms of flavonoids have been demonstrated to significantly suppress breast cancer resistance protein (BCRP/ABCG2), we hypothesized that kaempferol-3-O-b-D-robinoside-7-O-α-L-rhamnopyranoside may act as a BCRP-inhibitor. Mitoxantrone accumulation studies were performed in BCRP-overexpressing and BCRP-negative MCF7 cells using flow cytometric analysis. Robinin (5 and 50 mM) had no significant impacts on the BCRP-mediated mitoxantrone transport; on the contrary, the aglycone kaempferol produced increased accumulation of mitoxantrone. From these results, we suggest that the active component of natural hypoazotemic medicine Flaroninum™, robinin, may be a substrate of P-gp and its efflux outside of the cells mediated P-gp may contribute to its decreased intracellular concentration.

This study aimed to evaluate the influence of glutathione-based systems—poly(acrylic acid)-glutathione (PAA-GSH), chitosan-glutathione (ch.GSH), and free glutathione (GSH)—on the intestinal permeability of vingerbine alkaloids. The transepithelial transport of herbamine, herbadine, and vincarine was investigated using the Caco-2 cell monolayer model. Apical-to-basolateral and basolateral-to-apical fluxes were measured in the presence of PAA-GSH, ch.GSH, or free GSH to assess their effects on absorptive permeability and efflux-related processes. PAA-GSH significantly enhanced apical-to-basolateral transport, increasing permeability by 3.4-, 2.59-, and 1.52-fold for herbamine, herbadine, and vincarine, respectively, consistent with thiol-mediated reversible modulation of epithelial tight junctions. In contrast, ch.GSH reduced absorptive transport (1.28-, 1.67-, and 1.51-fold) and markedly decreased basolateral efflux, suggesting polymer–drug complex formation and reduced availability of free drug. Free GSH showed minimal influence on alkaloid permeability. These findings demonstrate that polymer architecture critically determines the intestinal transport behavior of vingerbine alkaloids. PAA-GSH acts as an effective permeation enhancer and represents a promising carrier for improving the intestinal delivery of tested compounds. Future studies will focus on developing optimized delivery systems for this anti-arrhythmic agent.

This study focuses on developing a polymer?clay hybrid system using a Georgian bentonite clay (Tikha-Ascane, TA) and Carbopol (CA) as a carrier for an essential oil (EO) derived from Matricaria chamomilla L. cultivated in East Georgia. EO was extracted via hydro distillation and characterized using GC?MS and FTIR techniques. The CA?TA and CA?TA?EO formulations were evaluated for key physicochemical parameters including pH, viscosity, rheology, spreadability, compatibility, moisture loss, uniformity and stability. The EO yield was 0.3 % from air-dried plant material. The main components were bisabolol oxide A (38.2 %), ?-bisabolol oxide B (12.91 %), (cis)-?-farnesene (11.8 %), ?-bisabolol (8.83 %), spathulenol (2.27 %), chamazulene (1.99 %), cis-ene-ynedicycloether (6.51 %) and ?-copaene (0.38 %). These results suggest that the local chamomile chemotype is rich in bisabolol oxide A. The optimized hydrogel formulation was homogeneous, stable and demonstrated favorable rheological properties, making it suitable for topical application. Chromatographic analysis confirmed the successful incorporation of the EO into the gel, which achieved an encapsulation efficiency of 58.34 %. Overall, the study confirms the compatibility of Georgian bentonite clay with the CA polymer, forming an effective matrix for volatile oil delivery in semisolid dosage forms.