Development and In Vitro - In Vivo Evaluation of Composite Hydrogel-Forming Microneedles Containing Diclofenac Sodium with Box-Behnken Design Using SLA 3D-Printed Microneedle Molds

Abstract

With developing manufacturing technologies, the use of 3D printers in microneedle production is becoming widespread. In recent years, microneedles have gained considerable popularity as dermal drug delivery systems. Hydrogel-forming microneedles (HFMs), a variant of microneedles, demonstrate distinctive features such as a high loading capacity, controlled drug release, and enhanced drug absorption. In this study, the molds, created using a Stereolithography (SLA) 3D printer, were utilized to create composite HFMs containing diclofenac sodium. Using an experimental design approach (Box–Behnken Design), the effects of different polymers on the in vitro performance of the developed HFMs, as well as the impact of polymer mixtures on microneedle formation were investigated. The skin penetration and drug release properties of the proposed formulations were assessed. Ex vivo studies were conducted on formulations to determine drug penetration and accumulation in tissue, and the MTT testing revealed non-cytotoxicity. Subsequently, in in vivo studies, the efficacy of the optimal formulation was assessed for the treatment of xylene-induced ear edema by contrasting it to the conventional dosage form. As a result, it was observed that HFMs could provide high amounts of drug accumulation in the skin tissue.