| |
[摘要]：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 beta-galactosidase (beta-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. beta-Gal activity assay was performed to evaluate transgene expression in vivo. The size of P/PM was similar to 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 beta-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. |
|
