ProT-Patch:\nA Smart Coated Polymeric Microneedle Enables\nNoninvasive Protein Delivery and Reprogramming of Epidermal Skin Identity

Microneedles have\nemerged as transformative devices for\nnoninvasive\ndrug delivery through skin; however, reported platforms suffer poor\nskin penetration, dosage inaccuracy, and/or complex fabrication. Herein,\nwe develop and validate a smart pH-responsive polymeric microneedle\n(proT-patch) for efficient drug delivery to the basal epidermal layer\nof the skin. The microneedle base offers high stiffness, while a variable\nneedle height design eludes the “bed of nails” effect.\nWith its stimuli-responsiveness, the microneedle coating enables drug\nrelease under specific pH conditions, enhancing dosage accuracy and\nminimizing biowaste. The performance of proT-patch is validated using <i>ex vivo</i> human skin by delivering Wnt5a, which switches on\nKeratin-9 expression, and is not expressed in nonplantar skin. Administering\nWnt5a-loaded proT-patch to skin enhanced Keratin-9 expression in basal\nepidermal keratinocytes compared to topical and unloaded controls.\nWith its facile fabrication, versatility, and exceptional performance,\nproT-patch shows immense potential as a next-generation, noninvasive\ntool for therapeutics, cosmetics, and vaccine delivery.