Nguyen Hiep X, Kipping Thomas, Banga Ajay K
Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA.
Faculty of Pharmacy, Phenikaa University, Yen Nghia, Ha Dong, Hanoi 12116, Vietnam.
Pharmaceutics. 2024 Jun 22;16(7):845. doi: 10.3390/pharmaceutics16070845.
This research presents the efficacy of polymeric microneedles in improving the transdermal permeation of methotrexate across human skin. These microneedles were fabricated from PLGA Expansorb 50-2A and 50-8A and subjected to comprehensive characterization via scanning electron microscopy, Fourier-transform infrared spectroscopy, and mechanical analysis. We developed and assessed a methotrexate hydrogel for physicochemical and rheological properties. Dye binding, histological examinations, and assessments of skin integrity demonstrated the effective microporation of the skin by PLGA microneedles. We measured the dimensions of microchannels in the skin using scanning electron microscopy, pore uniformity analysis, and confocal microscopy. The skin permeation and disposition of methotrexate were researched in vitro. PLGA 50-8A microneedles appeared significantly longer, sharper, and more mechanically uniform than PLGA 50-2A needles. PLGA 50-8A needles generated substantially more microchannels, as well as deeper, larger, and more uniform channels in the skin than PLGA 50-2A needles. Microneedle insertion substantially reduced skin electrical resistance, accompanied by an elevation in transepidermal water loss values. PLGA 50-8A microneedle treatment provided a significantly higher cumulative delivery, flux, diffusion coefficient, permeability coefficient, and predicted steady-state plasma concentration; however, there was a shorter lag time than for PLGA 50-2A needles, base-treated, and untreated groups ( < 0.05). Conclusively, skin microporation using polymeric microneedles significantly improved the transdermal delivery of methotrexate.
本研究展示了聚合物微针在改善甲氨蝶呤经皮渗透人皮肤方面的功效。这些微针由PLGA Expansorb 50 - 2A和50 - 8A制成，并通过扫描电子显微镜、傅里叶变换红外光谱和力学分析进行了全面表征。我们开发并评估了一种用于理化和流变学性质研究的甲氨蝶呤水凝胶。染料结合、组织学检查以及皮肤完整性评估表明PLGA微针可有效使皮肤形成微孔。我们使用扫描电子显微镜、孔隙均匀性分析和共聚焦显微镜测量了皮肤中微通道的尺寸。对甲氨蝶呤的皮肤渗透和分布进行了体外研究。PLGA 50 - 8A微针比PLGA 50 - 2A微针明显更长、更尖锐且力学性能更均匀。与PLGA 50 - 2A微针相比，PLGA 50 - 8A微针在皮肤中产生的微通道更多，且通道更深、更大且更均匀。微针插入显著降低了皮肤电阻，同时经皮水分流失值升高。PLGA 50 - 8A微针治疗提供了显著更高的累积释放量、通量、扩散系数、渗透系数和预测的稳态血浆浓度；然而，其滞后时间比PLGA 50 - 2A微针组、基础治疗组和未治疗组更短（<0.05）。总之，使用聚合物微针对皮肤进行微孔化显著改善了甲氨蝶呤的经皮递送。
