Local delivery of modified paclitaxel-loaded poly(ε-caprolactone)/pluronic F68 nanoparticles for long-term inhibition of hyperplasia

Abstract

The purpose of this research is to test the possibility of localized intravascular infusion of didodecyldimethylammonium bromide (DMAB)-modified paclitaxel-loaded poly(ε-caprolactone)/Pluronic F68 (PCL/F68) nanoparticles to achieve long-term inhibition of hyperplasia in a balloon-injured rabbit carotid artery model. Paclitaxel-loaded nanoparticles were prepared by modified solvent displacement method using commercial poly(lactide-co-glycolide) (PLGA) and self-synthesized PCL/F68, respectively. DMAB was adsorbed on the nanoparticle surface by electrostatic attraction between positive and negative charges to enhance arterial retention. Nanoparticles were found to be of spherical shape with a mean size of around 300 nm and polydispersity of less than 0.150. The surface charge was changed to positive values after the DMAB modification. The in vitro drug release profile of all nanoparticle formulation showed a biphasic release pattern. Drug release from DMAB-modified PCL/F68 nanoparticles (DPNP) was significantly slower than DMAB-modified PLGA nanoparticles (PGNP). After 90 days, DPNP group showed very significant inhibition of neointimal proliferation (p < 0.01), and PGNP group yielded significant inhibition of neointimal proliferation (p < 0.05), when compared with drug-free nanoparticles group. In conclusion, local delivery of paclitaxel-loaded DMAB-modified PCL/F68 nanoparticles was proven an effective means of long-term inhibition of hyperplasia in the rabbits. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2040–2050, 2009