Penetration of Topically Applied Polymeric Nanoparticles across the Epidermis of Thick skin

The natural barrier function of the epidermal skin layer 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 mechano-physical strategies on SC of thick skin for transdermal nanoparticle penetration. We characterize and compare two mechano-physical strategies, namely tape-stripping and microneedle abrasion, for epidermal disruption in both thick and thin skin. Furthermore, we examine the impact of SC disruption in thick and thin skin on the penetration of topically applied 100 nm sized polystyrene nanoparticles using an ex-vivo model. Our findings show that tape-stripping reduced the overall thickness of SC in thick skin by 87%, from 67.4 {+/-} 17.3 {micro}m to 8.2 {+/-} 8.5 {micro}m, whereas it reduced thin skin SC by only 38%, from 9.9 {+/-} 0.6 {micro}m to 6.2 {+/-} 3.2 {micro}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.