Yadav Tejpal, Yadav Hemant Kumar Singh, Gilhotra Ritu
Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, Jaipur, Rajasthan, 302017, India.
Department of Pharmaceutical Sciences, Indira Gandhi University, Meerpur, Rewari, Haryana, 122502, India.
Immunol Res. 2025 May 14;73(1):81. doi: 10.1007/s12026-025-09635-4.
Psoriasis is a chronic autoimmune skin disorder characterized by keratinocyte hyperproliferation, inflammation, and angiogenesis, significantly impacting patients' quality of life. Current therapeutic strategies, including topical corticosteroids, phototherapy, and systemic biologics, often present limitations such as adverse effects, high costs, and inadequate skin penetration. Transdermal drug delivery offers a promising alternative by enhancing localized drug bioavailability and minimizing systemic side effects. In this study, we investigated the antipsoriatic potential of pemetrexed disodium, a multitargeted antifolate agent, formulated as a transdermal patch in an imiquimod-induced psoriasis mouse model. The patches were prepared using a solvent evaporation technique and optimized for controlled drug release. Mice treated with pemetrexed-loaded transdermal patches exhibited significant dose-dependent reductions in psoriasis severity, as evidenced by improvements in Psoriasis Area and Severity Index (PASI) scores, histopathological analysis, and suppression of inflammatory cytokines (TNF-α, IL-6) assessed via qRT-PCR and ELISA. The highest concentration (0.16 mg/cm) demonstrated the most pronounced therapeutic effects, comparable to the standard ketoconazole treatment. These findings highlight the potential of pemetrexed disodium-loaded transdermal patches as an innovative, targeted therapy for psoriasis, warranting further clinical investigations.
银屑病是一种慢性自身免疫性皮肤病，其特征为角质形成细胞过度增殖、炎症和血管生成，严重影响患者的生活质量。目前的治疗策略，包括局部使用皮质类固醇、光疗和全身性生物制剂，常常存在诸如副作用、高成本和皮肤渗透性不足等局限性。经皮给药通过提高局部药物生物利用度并将全身副作用降至最低，提供了一种有前景的替代方法。在本研究中，我们在咪喹莫特诱导的银屑病小鼠模型中，研究了培美曲塞二钠（一种多靶点抗叶酸剂）制成的经皮贴剂的抗银屑病潜力。这些贴剂采用溶剂蒸发技术制备，并针对药物的控释进行了优化。用载有培美曲塞的经皮贴剂治疗的小鼠，银屑病严重程度出现了显著的剂量依赖性降低，这通过银屑病面积和严重程度指数（PASI）评分的改善、组织病理学分析以及通过qRT-PCR和ELISA评估的炎性细胞因子（TNF-α、IL-6）的抑制得以证明。最高浓度（0.16mg/cm）显示出最显著的治疗效果，与标准酮康唑治疗相当。这些发现突出了载有培美曲塞二钠的经皮贴剂作为银屑病创新靶向治疗方法的潜力，值得进一步进行临床研究。
