Nanopolymeric micelle effect on the transdermal permeability, the bioavailability and gene expression of plasmid.

This study attempts to investigate the transdermal permeability, the bioavailability and gene expression of plasmid formulated with nonionic poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) polymeric micelles (PM). Dynamic light scattering (DLS) and atomic force microscopy (AFM) were used to analyze the PM formulated pCMV-Lac Z (P/PM) containing the gene for β-galactosidase (β-Gal) driven by cytomegalovirus early promoter. Franz diffusion cell was used for in vitro transdermal permeability analysis. Real-time PCR was used to quantify the permeated plasmid in vitro and in vivo. β-Gal activity assay was performed to evaluate transgene expression in vivo. The size of P/PM was ~50 nm with round shape. PM significantly enhanced the in vitro transdermal permeability of plasmid in a direction- and temperature-dependent manner. Following transdermal application of P/PM, higher area under the curve (AUC(P/PM): 98.34 h·ng/mL) and longer half-life of plasmid were detected compared with that of plasmid alone (AUC(P): 10.12 h·ng/mL). Additionally, the β-Gal activity was significantly increased in skin, stomach, brain and spinal cord at both 48 and 72 h after P/PM application and in testis and spleen at 72 h postapplication. In conclusion, PM formulation enhanced the permeation of plasmid through skin into blood circulation, increasing its absorption and the transgene expression in various tissues.