Abstract
Local delivery of antiproliferative drugs encapsulated in biodegradable nanoparticles (NP) has shown promise as an experimental strategy for preventing restenosis development. A novel PDGFRβ-specific tyrphostin, AGL-2043, was formulated in polylactide-based nanoparticles and was administered intraluminally to the wall of balloon-injured rat carotid and stented pig coronary arteries. The disposition and elimination kinetics within the vessel wall, as well as the antirestenotic potential of the novel drug and delivery system, were evaluated. The efficacy and the local drug elimination kinetics were affected by the size of the NP and the drug-carrier binding mode. Despite similar arterial drug levels 90min after delivery in rats, small NP were more efficacious in comparison to large NP (90 and 160nm, respectively). AGL-2043 selectively inhibited vascular SMC in a dose-dependent manner. The antiproliferative effect of nanoencapsulated tyrphostin was considerably higher than that of surface-adsorbed drug. In the pig model, intramural delivery of AGL-2043 resulted in reduced in-stent neointima formation in the coronary arteries over control despite similar degrees of wall injury. The results of this study suggest that locally delivered tyrphostin AGL-2043 formulated in biodegradable NP may be applicable for antirestenotic therapy independent of stent design or type of injury.
Original language | English |
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Pages (from-to) | 451-461 |
Number of pages | 11 |
Journal | Biomaterials |
Volume | 26 |
Issue number | 4 |
DOIs | |
State | Published - Feb 2005 |
Keywords
- Controlled drug release
- Drug delivery
- In-stent restenosis
- Intimal hyperplasia
- Local delivery
- Nanoparticles
- Neointima
- Protein tyrosine kinase blocker
- Restenosis
- Smooth muscle cell
- Stent
- Tyrphostin