Targeted gene delivery to skin cells in vivo: a comparative study of liposomes and polymers as delivery vehicles.
Liposomes are microscopic lipid membrane vesicles that provide a current strategy for topical, dermal delivery of biologically active molecules. They have been successfully used for the delivery of various low and high molecular weight molecules into the skin, and as an alternative to virus-mediated delivery systems, have opened the field of dermal gene therapy. The present study was undertaken on 6-day-old rat pups to determine in vivo the efficacy of several liposome and nonliposome formulations, including phospholipid liposomes and their cationic or pegylated variants, nonionic liposomes and their cationic variant, PINC polymer (Protective, Interactive, Noncondensing polymers), and a propylene glycol:alcohol:water mixture (delivery vehicle for minoxidil) in delivering beta-galactosidase and luciferase reporter genes into skin cells. Based upon our observations of the expression of beta-galactosidase and luciferase reporter genes in skin cells, we report here that nonionic liposomes are the most efficient vehicle for transdermal delivery followed by nonionic/cationic and phospholipid (pegylated) liposomes. The propylene glycol:ethanol:water mixture and the PINC polymer were relatively inefficient in the delivery of beta-galactosidase or luciferase DNAs. This simple, noninvasive technique of using nonionic liposomes to deliver biomolecules provides an efficient delivery strategy for gene therapy and drug delivery to the dermal organ site.
Raghavachari
Nalini
N
McArdle Laboratory for Cancer Research, University of Wisconsin, 1400 University Avenue, Madison, WI 53706, USA.
Fahl
William E
WE
D000287:Administration, Topical; D000818:Animals; D000831:Animals, Newborn; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D005079:Excipients; D005260:Female; D018859:Hair Follicle / Q000502:physiology; D007700:Kinetics; D008081:Liposomes; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D014677:Pharmaceutical Vehicles; D010743:Phospholipids / Q000737:chemistry; D010957:Plasmids / Q000235:genetics; D011092:Polyethylene Glycols; D011108:Polymers; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000166:cytology*; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D005079:Excipients; D008081:Liposomes; D014677:Pharmaceutical Vehicles; D010743:Phospholipids; D011108:Polymers; D011092:Polyethylene Glycols; D004247:DNA; D008156:Luciferases; D001616:beta-Galactosidase