ProT-Patch: A Smart Coated Polymeric Microneedle Enables Noninvasive Protein Delivery and Reprogramming of Epidermal Skin Identity

High Resolution Image Download MS PowerPoint Slide Microneedles have emerged as transformative devices for noninvasive drug delivery through skin; however, reported platforms suffer poor skin penetration, dosage inaccuracy, and/or complex fabrication. Herein, we develop and validate a smart pH-responsive polymeric microneedle (proT-patch) for efficient drug delivery to the basal epidermal layer of the skin. The microneedle base offers high stiffness, while a variable needle height design eludes the “bed of nails” effect. With its stimuli-responsiveness, the microneedle coating enables drug release under specific pH conditions, enhancing dosage accuracy and minimizing biowaste. The performance of proT-patch is validated using ex vivo human skin by delivering Wnt5a, which switches on Keratin-9 expression, and is not expressed in nonplantar skin. Administering Wnt5a-loaded proT-patch to skin enhanced Keratin-9 expression in basal epidermal keratinocytes compared to topical and unloaded controls. With its facile fabrication, versatility, and exceptional performance, proT-patch shows immense potential as a next-generation, noninvasive tool for therapeutics, cosmetics, and vaccine delivery.