Gout is a pathological condition caused by monosodium urate crystal deposition in tissues. Allopurinol, the first-line therapy, inhibits xanthine oxidase but may be ineffective due to reduced conversion to oxypurinol (OXY). Current delivery routes for OXY, including oral and intravenous routes, have drawbacks such as poor solubility and patient discomfort. This study developed a delivery system integrating thermosensitive gel (TRG) containing OXY with polymeric solid microneedles (PSMNs). Molecular docking demonstrated high-affinity binding interactions between OXY and Pluronic (−2.5). The TRG, formulated with Pluronic F127 and F68, was assessed for gelation temperature, pH, spreadability, and bioadhesive strength. PSMN, made from poly(vinyl alcohol) and polyvinylpyrrolidone K-30 with citric acid, was evaluated for mechanical strength and skin penetration. In vitro hemolysis activity, drug release, and ex vivo permeation studies were conducted. Molecular docking results showed stable binding with an affinity of −2.5 between the ligands of OXY and Pluronic. The TRG formulation exhibited promising characteristics for transdermal drug delivery. PSMN demonstrated good mechanical strength and was able to penetrate up to 504 μm. Hemolysis testing showed that PSMN and TSG were safe with a hemolysis ratio of less than 5%. In vitro drug release studies showed a high OXY release of 2.24 ± 0.26 mg with the highest concentration of Pluronic F68, displaying a sustained release profile. Ex vivo permeation studies showed a significant difference (p < 0.05) between OXY permeation without and with PSMN combination. PSMN increased OXY permeation by 79−81% compared to permeation without PSMN. This study successfully developed a TRG formulation combined with PSMN to enhance transdermal delivery of OXY. These results suggest a promising new route for OXY delivery, potentially offering a more efficient and user-friendly treatment for chronic gout. Further in vivo studies are needed to evaluate the efficacy, pharmacokinetics, pharmacodynamics, drug interactions, and toxicity for further clinical applications.
