Non-viral eNOS gene delivery and transfection with stents for the treatment of restenosis.
BACKGROUND
In this study, we have examined local non-viral gene delivery, transfection, and therapeutic efficacy of endothelial nitric oxide synthase (eNOS) encoding plasmid DNA administered using coated stents in a rabbit iliac artery restenosis model.


METHODS
Lipopolyplexes (LPPs) with eNOS expressing plasmid DNA were immobilized on stainless steel stents using poly(D,L-lactide-co-glycolide) (PLGA) and type B gelatin coatings. The gene-eluting stents were implanted bilaterally in the denuded iliac arteries and eNOS transfection and therapeutic efficacy were examined 14 days after implantation.


RESULTS
The results show that non-viral lipopolyplex-coated stents can efficiently tranfect eNOS locally in the arterial lumen assessed by PCR and ELISA. Human eNOS ELISA levels were significantly raised 24 hours after transfection compared to controls (125 pg eNOS compared to <50 pg for all controls including naked DNA). Local eNOS production suppressed smooth muscle cell proliferation and promoted re-endothelialization of the artery showing a significant reduction in restenosis of 1.75 neointima/media ratio for stents with lipoplexes encoding eNOS compared with 2.3 neointima/media ratio for stents with lipoplexes encosing an empty vector.


CONCLUSIONS
These results support the hypothesis that a potent non-viral gene vector encoding for eNOS coated onto a stent can inhibit restenosis through inhibition of smooth muscle cell growth and promotion of a healthy endothelium.
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; D023903:Coronary Restenosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005780:Gelatin / Q000737:chemistry; D006801:Humans; D007083:Iliac Artery / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011108:Polymers / Q000737:chemistry; D011817:Rabbits; D012449:Safety; D015607:Stents; D014162:Transfection / Q000379:methods*; D019076:Transgenes / Q000235:genetics
D011108:Polymers; C507253:poly(beta-amino ester); D005780:Gelatin; D004247:DNA; D052250:Nitric Oxide Synthase Type III