Abstract
We propose a polymeric nanovehicles (PNVs)-based enhanced transdermal delivery platform. A technical advance can be found in that delivery efficiency is significantly enhanced by effective adhesion of PNVs to the cell membrane, which is characterized noninvasively by using a confocal laser scanning microscopy (CLSM)-based skin visualization technique. To this end, the PNVs with a soft core phase 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 softness of PNVs 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 transactivating transcriptional activator (TAT)-decorated soft 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, CLSM-based noninvasive visualization of a fluorescent drug probe in the skin showed that the adhesiveness and softness of the PNVs contributed directly to the enhancement of transdermal delivery.
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