Liposomal surface coatings of metal stents for efficient non-viral gene delivery to the injured vasculature

• Published in: Journal of controlled release Vol. 167; no. 2; pp. 109 - 119
• Main Authors: Ganly, Sandra, Hynes, Sean O., Sharif, Faisal, Aied, Ahmed, Barron, Valerie, McCullagh, Karl, McMahon, Jill, McHugh, Peter, Crowley, Jim, Wang, Wenxin, O'Brien, Timothy, Greiser, Udo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 28-04-2013
• Subjects: Animals; beta-Galactosidase - genetics; Cells, Cultured; Cercopithecus aethiops; Chromium Alloys; DNA - administration & dosage; DNA - chemistry; Green Fluorescent Proteins - genetics; Humans; Iliac Artery - injuries; Iliac Artery - metabolism; Lipid; Lipids - chemistry; Lipoplexes; Liposomes; Male; Myocytes, Smooth Muscle; Non-viral gene therapy; Plasmids; Rabbits; Stainless Steel; Stent; Stents; Surface Properties; Transfection - methods; Vasculature; Vero Cells; Stent; Non-viral gene therapy; Lipid; Vasculature; Lipoplexes
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2013.01.036

Despite the widespread use of drug eluting stents (DES), in-stent restenosis (ISR), delayed arterial healing and thrombosis remain important clinical complications. Gene-eluting stents (GES) represent a potential strategy for the prevention of ISR by delivering a therapeutic gene via a vector from the stent surface to the vessel wall. To this end, a model in vitro system was established to examine whether cationic liposomes could be used for gene delivery to human artery cells. Three different formulations were compared (DOTMA/DOPE, DDAB/DOPE or DDAB/POPC/Chol) to examine the effects of different cationic and neutral lipids on the transfection efficiency of lipoplex-coatings of metal surfaces. Upon completion of the characterization and optimization of the materials for gene delivery in vitro, these coatings were examined on a range of stents and deployed in a rabbit iliac artery injury model in vivo. Maximal transfection efficiencies for all coatings were observed on day 28, followed by declining, but persisting gene expression 42days after stent placement, thereby, presenting liposomal coatings for gene eluting stents as treatment options for clinical complications associated with stenting procedures.
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