Application of membrane-based dendrimer/DNA complexes for solid phase transfection in vitro and in vivo.
In this study a general description of the use of solid support membranes as the device for DNA delivery mediated by PAMAM dendrimers is presented. In contrast to the other DNA carriers, dendrimer/DNA complexes retain the ability to transfect after drying, which enabled coating or incorporation of complexes into poly(DL-lactide-co-glycolide) or collagen-based bioerodable membranes. These studies provide support for the use of this technology for in vitro and in vivo transfection of skin cells. Expression of luciferase or green fluorescent protein from pCF1-Luc and pEGFP1 plasmids indicated that dendrimer/DNA complexes can mediate transfection after dissociation from the solid support and/or when retained on the surface of the membranes. Modification of the membranes by incorporation of an anionic lipid, phosphatidyl glycerol (PG) at 1-5% concentrations, resulted in more efficient in situ transfection, particularly with dendrimer/DNA complexes formed at the low charge ratios (1-5). We also report data supporting the feasibility of membrane-based dendrimer/DNA complexes, particularly formed at lower than neutralizing conditions, for topical in vivo delivery of DNA to hairless mouse skin.
Bielinska
A U
AU
Department of Internal Medicine, University of Michigan Health System, Ann Arbor 48109, USA.
Yen
A
A
Wu
H L
HL
Zahos
K M
KM
Sun
R
R
Weiner
N D
ND
Baker
J R
JR
Roessler
B J
BJ
D000287:Administration, Topical; D000818:Animals; D002460:Cell Line; D004247:DNA / Q000737:chemistry*; D004337:Drug Carriers; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000737:chemistry; D008156:Luciferases / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D008567:Membranes, Artificial; D051379:Mice; D008812:Mice, Hairless; D010715:Phosphatidylglycerols / Q000737:chemistry; D010957:Plasmids; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D012867:Skin / Q000378:metabolism; D014162:Transfection
D004337:Drug Carriers; D008164:Luminescent Proteins; D008567:Membranes, Artificial; D010715:Phosphatidylglycerols; D011108:Polymers; D049452:Green Fluorescent Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004247:DNA; D008156:Luciferases