Development of a functionalized polymer for stent coating in the arterial delivery of small interfering RNA.
In patients receiving drug eluting stents, there is a growing concern about both the long-term toxicity/degradability of the polymers used for the coating, and the nature of the therapeutic agents. We hypothesized that the use of a functionalized biocompatible polymer for a stent coating could be appropriate for local arterial therapy. A cationized pullulan hydrogel was thus prepared to cover bare metal stents that could be further loaded with small interfering RNA (siRNA) targeted at MMP2 for gene silencing in vascular cells. The efficient coverage of the stent struts by a smooth polymeric layer, which can withstand the crimping of the stent on a balloon-catheter and its deployment, was demonstrated by fluorescence microscopy, scanning electron microscopy, and atomic force microscopy. The release of siRNA from the stents was modulated by the presence of the cationic groups, as compared to noncationized pullulan hydrogel. In vivo implantation of coated stents was successful and cationized pullulan-based hydrogels loaded with siRNA in rabbit balloon-injured carotid arteries induced an uptake of siRNA into the arterial wall and a decrease of pro-MMP2 activity. These results suggest that cationized pullulan-based hydrogel could be used as a new biocompatible and biodegradable stent coating for local gene therapy in the arterial wall.
San Juan
Aurélie
A
Inserm, U698, Bio-ingénierie Cardiovasculaire, Université Paris 7, Paris, France.
Bala
Madiha
M
Hlawaty
Hanna
H
Portes
Patrick
P
Vranckx
Roger
R
Feldman
Laurent J
LJ
Letourneur
Didier
D
D000818:Animals; D002339:Carotid Arteries / Q000502:physiology / Q000601:surgery*; D020099:Coated Materials, Biocompatible / Q000008:administration & dosage* / Q000138:chemical synthesis*; D055808:Drug Discovery / Q000379:methods; D054855:Drug-Eluting Stents; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D011817:Rabbits
D020099:Coated Materials, Biocompatible; D011108:Polymers; D034741:RNA, Small Interfering