Water-Soluble, Enzyme-Degradable, and Hydrolyzable STAR Particles for Enhanced Drug Delivery to Skin.

Drug delivery via skin enables local delivery that targets the skin and systemic delivery that avoids limitations of oral and parenteral administration. However, this route is often constrained by the skin's natural barrier, the stratum corneum. STAR particles with microscopic needles can painlessly puncture the skin to increase skin permeability, but they have previously been made of non-biodegradable materials, such as ceramic and metal. To address potential environmental and safety concerns, we introduce biodegradable polymer STAR particles that are water-soluble (poly(vinyl alcohol), PVA), enzyme-degradable (cellulose acetate, CA), or hydrolyzable (polylactic acid, PLA). STAR particles were fabricated using femtosecond laser micromachining to achieve dimensional features and sharp tips. We characterized their mechanical properties, and confirmed their skin-puncturing ability through gentian violet staining. We also evaluated STAR particle-enhanced delivery of three model drugs in porcine skin ex vivo: tacrolimus with PVA STAR particles, methotrexate with CA STAR particles, and copper tripeptide-1 with PLA STAR particles. Skin treatment with polymer STAR particles increased intradermal drug delivery by up to 37-fold, depending on the drug type and the STAR particle material and application duration. We conclude that biodegradable polymer STAR particles can address environmental and safety concerns while enhancing drug delivery to skin.