Abstract
This investigation aimed to enhance transdermal methotrexate delivery through human skin by employing Dr. Pen microneedles and poly(d,l-lactide-co-glycolide) acid microparticles formulated from eight polymer grades (Expansorb DLG 95-4A, DLG 75-5A, DLG 50-2A, DLG 50-5A, DLG 50-8A, DLG 50-6P, DLG 50-7P, and DLL 10-15A). A comprehensive characterization of the microparticles was performed, encompassing various parameters such as size, charge, morphology, microencapsulation efficiency, yield, release kinetics, and chemical composition. The efficacy of microneedles in disrupting skin integrity was demonstrated by scanning electron microscopy, dye binding, histological examination, confocal laser microscopy, and pore size analysis. Microneedle-mediated skin microporation led to a substantial reduction in skin electrical resistance and a concomitant increase in transepidermal water loss. In vitro permeation experiments using human skin delivered microparticles into microporated skin and demonstrated a considerable difference in methotrexate delivery among the polymer groups. Microneedle treatment significantly amplified cumulative drug delivery, steady-state flux, diffusion coefficient, permeability coefficient, and drug concentration within skin layers while concurrently diminishing lag time (p < 0.05). Furthermore, a robust correlation was established between microparticle properties (cumulative release, release rate, encapsulation efficiency) and drug deposition in the skin. In conclusion, the synergistic combination of Dr. Pen microneedles and PLGA microparticles facilitated enhanced and regulated transdermal methotrexate delivery.
Published Version
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