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 #uorescent 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. Modi"cation of the membranes by incorporation of an anionic lipid, phosphatidyl glycerol (PG) at 1}5% concentrations, resulted in more e$cient 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. ( 2000 Elsevier Science Ltd. All rights reserved.