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

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.