title: Intramural injection of biodegradable microspheres as a local drug-delivery system to inhibit neointimal thickening in a rabbit model of balloon angioplasty.
abstract: Restenosis remains the major limitation of coronary angioplasty. The objective of this study was to develop microspheres able to be delivered at the angioplasty site for long-term drug release and to test their effects in a model of balloon angioplasty. Polylactic-co-glycolide acid microspheres (5-10 microm in diameter) were prepared by using an oil-in-water emulsion-solvent evaporation method. In vitro experiments with hydrocortisone-loaded microspheres revealed a hydrocortisone release for 4 weeks. We studied the in vivo effect of injection of microspheres into the arterial wall of New Zealand White rabbits by using a perforated balloon. Deep penetration of microspheres in the arterial wall was documented immediately after angioplasty. Intimal hyperplasia was assessed in iliac arteries 4 weeks after angioplasty. The morphometric analysis was performed in four groups of animals; the first group was subjected only to conventional angioplasty (control, n = 10), whereas the other three groups after conventional angioplasty were received perforated balloon angioplasty with saline (n = 10), microspheres (n = 10), or hydrocortisone-loaded microspheres (n = 7). Intramural injection of saline did not induce greater intimal hyperplasia compared with control (0.17 +/- 0.03 vs. 0.18 +/- 0.03 mm2, respectively). Microspheres injection was associated with a trend toward a greater degree of intimal hyperplasia that did not reach statistical significance. Hydrocortisone-loaded microspheres were associated with a significant reduction in intimal hyperplasia compared with unloaded microspheres (0.16 +/- 0.02 vs. 0.26 +/- 0.03 mm2, respectively). The polylactic-co-glycolide acid microspheres are well tolerated, easily injected into the arterial wall, and the increase of intimal hyperplasia is easily inhibited by release of hydrocortisone for 4 weeks after initial injury.
authors.affiliation: University and CHRU de Lille, France.
authors.forename: F
authors.initials: F
authors.lastname: Valéro
authors.forename: M
authors.initials: M
authors.lastname: Hamon
authors.forename: C
authors.initials: C
authors.lastname: Fournier
authors.forename: T
authors.initials: T
authors.lastname: Meurice
authors.forename: B
authors.initials: B
authors.lastname: Flautre
authors.forename: E
authors.initials: E
authors.lastname: Van Belle
authors.forename: J M
authors.initials: JM
authors.lastname: Lablanche
authors.forename: B
authors.initials: B
authors.lastname: Gosselin
authors.forename: C
authors.initials: C
authors.lastname: Bauters
authors.forename: M
authors.initials: M
authors.lastname: Bertrand
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000097:blood; D001672:Biocompatible Materials; D003327:Coronary Disease / Q000517:prevention & control*; D016503:Drug Delivery Systems; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000097:blood; D006965:Hyperplasia / Q000517:prevention & control; D007083:Iliac Artery / Q000187:drug effects* / Q000473:pathology; D019344:Lactic Acid; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011817:Rabbits; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006854:Hydrocortisone