طراحي، تهيه و ارزيابي خواص ميكروسوزن بر پايه هيدروژل ژلما/كتيراي حاوي وانيليك اسيد به منظور كاربرد در درمان بيماري آرتريت روماتوئيد

Microneedle arrays are advanced transdermal drug delivery systems capable of penetrating the outermost layer of the skin (stratum corneum) an‎d delivering therapeutic agents into the body through a minimally invasive, painless an‎d bloodless approach. These systems enhance therapeutic efficacy by improving drug bioavailability compared to oral an‎d local formulations an‎d reducing adverse effects on non-target tissues such as gastrointestinal complications an‎d osteoporosis. The application of microneedles for the treatment of diseases such as Rheumatoid Arthritis—that conventional therapies are often associated with complications including gastrointestinal disorders an‎d osteoporosis—represents a promising therapeutic strategy. The aim of the present study was design an‎d fabricate a GelMA/Tragacanth-based hydrogel microneedle for the controlled delivery of Vanillic acid as an anti-inflammatory agent. Vanillic acid, a plant-derived compound with well-known antioxidant an‎d anti-inflammatory properties, was employed as the therapeutic agent. Initially, GelMA was synthesized an‎d characterized using Fourier-transform infrared (FTIR) spectroscopy an‎d nuclear magnetic resonance (NMR) analysis. Subsequently, hybrid GelMA/Tragacanth hydrogels were prepared at various concentrations. At higher Tragacanth contents, the formation of a stable hybrid hydrogel was not feasible. By reducing the Tragacanth concentration, a 4:1 GelMA: Tragacanth ratio was identified as the maximum Tragacanth content capable of forming a stable hybrid hydrogel. Accordingly, GelMA:Tragacanth ratios of 4, 6, an‎d 8 (named as 1G-0.250Tg, 1G-0.166Tg an‎d 1G-0.125Tg, respectively) were selec‎ted for further eva‎luation. FTIR an‎d NMR analyses confirmed the formation of intermolecular interactions between GelMA an‎d Tragacanth. Hydrogels containing Tragacanth exhibited higher swelling ratios (approximately1000 times their dry weight) compared with GelMA sample (approximately 400 times its dry weight). Scanning electron microscopy revealed that the 1G-0.250Tg sample possessed smaller pore sizes (approximately 128 ± 33 μm) relative to the other formulations. Mechanical eva‎luations demonstrated that Tragacanth-containing samples exhibited enhanced compressive strength compared with the Tragacanth-free hydrogel. Notably, the compressive strength of the 1G-0.250Tg sample (49 ± 3 kPa) was significantly greater than that of the GelMA sample (15 ± 1 kPa). Drug release studies indicated sustained an‎d controlled release of Vanillic acid from all formulations. Thermal analysis further demonstrated that the incorporation of Tragacanth improved the thermal stability of the hybrid hydrogel compared to GelMA sample. All samples exhibited appropriate injectability, rheological behavior, an‎d biocompatibility properties. Based on the overall physicochemical an‎d biological eva‎luations, the 1G-0.250Tg formulation was selec‎ted as the optimal GelMA/Tragacanth hybrid, an‎d its antioxidant activity was confirmed. Following the design an‎d fabrication of the microneedle mold, GelMA, Tragacanth an‎d hybrid GelMA/Tragacanth microneedle arrays were fabricated with an approximate height of 550 μm an‎d a base diameter of 300 μm. Structural characterization an‎d compressive strength eva‎luation demonstrated that the hybrid microneedle array exhibited higher mechanical strength an‎d sharper needle tips compared with the other two arrays. Penetration studies conducted using Parafilm® (as a skin model) an‎d rat cadaver skin confirmed the effective inser‎tion capability of the hybrid GelMA/Tragacanth microneedle array. Furthermore, drug release eva‎luation using a Franz diffusion cell system revealed that approximately 96% of Vanillic acid was released within 24 hours.

شيدا لباف , ژاله ورشوساز

نفيسه اسمعيل

مهشيد خرازيهاي اصفهاني , محمد خدائي , مهدي مهدي خاني