Noninvasive Visualization of Enhanced Transdermal Delivery Using Skin-Adhesive Polymeric Nanovehicles

Abstract

A transdermal delivery system based on skin-adhesive deformable polymeric nanovehicles (PNVs) that provides remarkably enhanced drug delivery efficiency is reported. Core-phase deformable skin-adhesive PNVs were fabricated through co-assembly of two amphiphilic triblock copolymers, poly(ethylene oxide)-b-poly(ε-caprolactone)-b-poly(ethylene oxide) (PEO-b-PCL-b-PEO) and poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-b-PPO-b-PEO). The deformability of the PNV cores was tuned successfully, while maintaining the particle size at ~110 nm, by incorporation of PEO-b-PPO-b-PEO into the PNVs to a volume fraction of 0.3. Through an ex vivo skin penetration test, we showed that transactivator of transcription (TAT)-decorated deformable PNVs could not only exert strong adhesion to skin but also increase cellular uptake, leading to a transdermal delivery efficiency that is twice that of a hard PNV control. Moreover, noninvasive visualization of a fluorescent drug probe in the skin via confocal laser scanning microscopy analysis showed that the skin adhesiveness and deformability of the PNVs contributed directly to the enhancement of transdermal delivery.