Penetration of topically applied polymeric nanoparticles across the epidermis of thick skin from rat

The barrier function of the epidermis poses a significant challenge to nanoparticle-mediated topical delivery. A key factor in this barrier function is the thickness of the stratum corneum (SC) layer within the epidermis, which varies across different anatomical sites. The epidermis from the palms and soles, for instance, have thicker SC compared to those from other areas. Previous studies have attempted to bypass the SC layer for nanoparticle penetration by using physical disruption; however, these studies have mostly focused on non-thick skin. In this study, we investigate the role of SC-disrupting mechano-physical strategies (tape-stripping and microneedle abrasion) on thick and thin skin, in allowing transdermal penetration of topically applied nanoparticles using an ex-vivo skin model from rat. Our findings show that tape-stripping reduced the overall thickness of SC in thick skin by 87%, from 67.4 +/- 17.3 mu m to 8.2 +/- 8.5 mu m, whereas it reduced thin skin SC by only 38%, from 9.9 +/- 0.6 mu m to 6.2 +/- 3.2 mu m. Compared to non-thick skin, SC disruption in thick skin resulted in higher nanoparticle diffusion. Tape-stripping effectively reduces SC thickness of thick skin and can be potentially utilized for enhanced penetration of topically applied nanoparticles in skin conditions that affect thick skin.