In vitro and in vivo studies of local arterial gene delivery and transfection using lipopolyplexes-embedded stents.
Gene-eluting stents can have profound impact in the treatment of coronary restenosis, especially when the encoded protein can re-endothelialize the arterial lumen. In this study, we have examined gene delivery in vitro and in vivo using poly(beta-amino ester) (PbAE) precondensed plasmid DNA-containing cationic liposomes or lipopolyplexes (LPP) immobilized on stainless steel meshes and stents using gelatin coatings. In vitro studies using LPP-immobilized on 50 mm round meshes using type A and B gelatin coatings showed that LPP were efficiently internalized in human aortic smooth muscle cells (SMC) over time, leading to green fluorescent protein (GFP) expression. Type B gelatin coating was found to be more effective in intracellular delivery and transgene expression efficiency and, as such, was used for stent coating. In vivo studies, carried out in iliac artery restenosis model in New Zealand white rabbits, also showed GFP expression in arterial tissues after 24 h of implantation. Based on these encouraging preliminary results, LPP-based formulations can serve as a safe and effective nonviral gene delivery system for effective treatment of coronary restenosis.
Brito
Luis A
LA
Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Chandrasekhar
Saradha
S
Little
Steven R
SR
Amiji
Mansoor M
MM
D000818:Animals; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D004247:DNA / Q000235:genetics; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005780:Gelatin / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007083:Iliac Artery / Q000187:drug effects / Q000378:metabolism*; D008081:Liposomes / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D010316:Particle Size; D010957:Plasmids / Q000235:genetics; D011108:Polymers / Q000494:pharmacology*; D011817:Rabbits; D013193:Stainless Steel / Q000494:pharmacology; D015607:Stents; D013499:Surface Properties / Q000187:drug effects; D014162:Transfection / Q000379:methods*
D020099:Coated Materials, Biocompatible; D008081:Liposomes; D011108:Polymers; C507253:poly(beta-amino ester); D013193:Stainless Steel; D049452:Green Fluorescent Proteins; D005780:Gelatin; D004247:DNA; D016650:Fluorescein-5-isothiocyanate