Dissolving hyaluronic acid microparticles improve skin barrier function, hydration, and elasticity in a randomized split-face clinical trial

Abstract

The stratum corneum is a major barrier to topical delivery. We developed dissolving, star-shaped hyaluronic acid (HA) microparticles designed for fingertip rolling to create transient microchannels and support topical penetration. HA microparticles were fabricated using star-shaped micromolds and evaluated for geometry, mechanical strength, and water-triggered dissolution. Ex vivo porcine skin was used to assess microchannel formation and fluorescent tracer penetration. In a randomized, assessor-blinded, split-face clinical trial, 20 healthy women aged 47–58 years applied an oil-based serum with or without HA microparticles twice daily for 4 weeks. HA microparticles showed uniform geometry, reproducible fracture force, and rapid dissolution in water. Ex vivo application generated visible microchannels and increased tracer penetration depth by approximately 3.8-fold versus the no-microparticle control. Clinically, the HA microparticle-treated side showed greater improvements than the no-microparticle control regimen at 4 weeks in the primary outcomes of TEWL and hydration, with additional exploratory improvements in elasticity, wrinkle, dermal density, pore, and pigmentation indices. No adverse events were observed. These findings suggest that dissolving star-shaped HA microparticles are a practical, device-free, and well-tolerated strategy for supporting topical penetration ex vivo and improving skin condition under the tested regimen. Trial registration: Clinical Research Information Service (CRIS), KCT0011849, registered on April 14, 2026.