A highly robust approach to fabricate the mass-customizable mold of sharp-tipped biodegradable polymer microneedles for drug delivery.

A skin-perforable dissolving microneedle is a promising mediator for painlessly delivering active pharmaceutical compounds across the skin. All the microneedle manufacturing processes so far, however, are much sensitive to input variation and unfavorable for make-to-order approach. Here, a robust method for fabricating mass-customizable master molds is developed to prepare sharp-tipped biodegradable polymer microneedles. Our approach combines the predrying and chip casting (PCC) of an ultrathick photoresist layer with a substrateless, inclined, and rotational exposure (SIR exposure). The PCC achieves the uniform reduction of solvent across the photoresist thickness which is critically required for the formation of a sharp tip; the SIR exposure creates master molds whose geometry is easily customizable and virtually insensitive to a variation in ultraviolet (UV) exposure dose. A theoretical model for the spatiotemporal distribution of UV dose under SIR exposure is established to show the technological superiority of our method. Next, our method's applicability is proven by fabricating a set of poly(lactic-co-glycolic) acid (PLGA) microneedles and performing both porcine skin penetration test and their in vitro degradation test. Our approach is verified to be robust in manufacturing mass-customizable molds for skin-perforable dissolving microneedles and to have high compatibility with almost all existing biodegradable polymers. The findings of this study lead to both a significant growth of dissolving microneedle-mediated drug delivery and better understanding of drug release kinetics.