title: Palmitic acid-modified poly-L-lysine for non-viral delivery of plasmid DNA to skin fibroblasts.
abstract: Palmitic acid conjugates of poly-L-lysine (PLL-PA) were prepared, and their ability to deliver plasmid DNA into human skin fibroblasts was evaluated in vitro. The conjugates were capable of condensing a 4.7 kb plasmid DNA into 50-200 nm particles (mean +/- SD = 112 +/- 34 nm), which were slightly smaller than the particles formed by PLL (mean +/- SD = 126 +/- 51 nm). Both PLL and PLL-PA were readily taken up by the cells, but PLL-PA delivered the plasmid DNA into a higher proportion of cells. DNA delivery was found to be reduced by endocytosis inhibitor Brefeldin A, suggesting an active mechanism of particle uptake. Using enhanced green fluorescent protein (EGFP) as a reporter gene, PLL-PA was found to give the highest number of EGFP-positive cells among several carriers tested, including polyethyleneimine, Lipofectamine-2000, and an adenovirus. Although some carriers gave a higher percentage of EGFP-positive cells than PLL-PA, they were also associated with higher toxicities. We conclude that PLL-PA is a promising gene carrier for non-viral modification of human fibroblasts.
authors.affiliation: Department of Biomedical Engineering, University of Alberta, Edmonton, AB, Canada.
authors.forename: Meysam
authors.initials: M
authors.lastname: Abbasi
authors.forename: Hasan
authors.initials: H
authors.lastname: Uludag
authors.forename: Vanessa
authors.initials: V
authors.lastname: Incani
authors.forename: Cori
authors.initials: C
authors.lastname: Olson
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Lin
authors.forename: Başak Açan
authors.initials: BA
authors.lastname: Clements
authors.forename: Dorothy
authors.initials: D
authors.lastname: Rutkowski
authors.forename: Aziz
authors.initials: A
authors.lastname: Ghahary
authors.forename: Michael
authors.initials: M
authors.lastname: Weinfeld
mesh_terms: D002478:Cells, Cultured; D004247:DNA / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism*; D018014:Gene Transfer Techniques; D006801:Humans; D015394:Molecular Structure; D019308:Palmitic Acid / Q000737:chemistry* / Q000378:metabolism; D010316:Particle Size; D010957:Plasmids / Q000235:genetics; D011107:Polylysine / Q000737:chemistry* / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D013997:Time Factors
chemical_list: D004337:Drug Carriers; D011107:Polylysine; D019308:Palmitic Acid; D004247:DNA