title: Nanopolymeric micelle effect on the transdermal permeability, the bioavailability and gene expression of plasmid.
abstract: 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.
authors.affiliation: College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yaw-Chong
authors.initials: YC
authors.lastname: Tong
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Yu
authors.forename: Shwu-Fen
authors.initials: SF
authors.lastname: Chang
authors.forename: Jiahorng
authors.initials: J
authors.lastname: Liaw
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D055598:Chemical Phenomena; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006207:Half-Life; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D049329:Nanostructures / Q000737:chemistry*; D010957:Plasmids / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D011409:Propylene Glycols / Q000737:chemistry*; D011994:Recombinant Proteins / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D012869:Skin Absorption; D013047:Specific Pathogen-Free Organisms; D014018:Tissue Distribution; D019076:Transgenes
chemical_list: D008823:Micelles; C116176:PEO-PPO-PEO; D011409:Propylene Glycols; D011994:Recombinant Proteins; D011092:Polyethylene Glycols