Thermostable hyaluronic acid-based dissolving microneedles with high-loading capacity: design, optimization, and transdermal delivery of anti-aging ingredients.

This study developed a thermostable, high-loading dissolving microneedle (DMN) system for the transdermal delivery of anti-aging ingredients, 3-O-ethyl ascorbic acid (EAC) and acetyl hexapeptide-8 (AH-8). By using a composite matrix of hyaluronic acid (HA) and polyvinyl alcohol (PVA) in a 3:2 ratio and optimizing a two-step vacuum-assisted micromolding process, we successfully addressed key fabrication challenges, reducing drying time to 2 h and eliminating structural defects. A split-needle design further increased drug loading, reaching 40% for EAC and 20% for AH-8. The resulting DMNs showed excellent mechanical properties, skin penetration efficiency, and biocompatibility in human subjects. In vitro permeation studies using Bama miniature pig skin revealed release profiles influenced by drug-polymer interactions. Despite these differences, both compounds achieved higher cumulative transdermal delivery (EAC: 17.25%; AH-8: 11.29%) than their aqueous solutions. In a UV/D-galactose-induced photoaging mouse model, both EAC-DMNs and AH-8-DMNs significantly reduced visible signs of aging, including wrinkles, skin laxity, and erythema. They also improved skin elasticity and hydration, reversed pathological thickening, and restored oxidative balance by increasing SOD activity and lowering MDA levels. This work provides a scalable, biocompatible, and effective DMN platform, supporting its potential for clinical anti-aging applications.