, Volume 24, Issue 5, pp 955-962
Date: 20 Mar 2007

Modified Paclitaxel-loaded Nanoparticles for Inhibition of Hyperplasia in a Rabbit Arterial Balloon Injury Model

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Purpose

This study tested the possibility of localized intravascular infusion of positive charged paclitaxel-loaded nanoparticles (NPs) to better prevent neointimal formation in a rabbit carotid artery injury model.

Materials and Methods

NPs were prepared by oil–water emulsion/solvent evaporation technique using biodegradable poly (lactide-co-glycolide) (PLGA). A cationic surfactant, didodecyldimethylammonium bromide (DMAB), was absorbed on the NP surface by electrostatic attraction between positive and negative charges. NPs were characterized in such aspects as size, surface morphology, surface charges as well as in vitro drug release profile. Balloon injured rabbit carotid arteries were treated with single infusion of paclitaxel-loaded NP suspension and observed for 28 days. The inhibitory effects of NPs on neointima formation were evaluated as end-point.

Results

NPs showed spherical shape with a diameter ranging from 200 to 500 nm. Negatively charged PLGA NPs shifted to positive after the DMAB modification. The in vitro drug release profile showed a biphasic release pattern. Morphometric analyses on the retrieved artery samples revealed that the inhibitory effect of intima proliferation was dose-dependent. At a concentration of 30 mg ml−1, NP infusion completely inhibited intima proliferation in a rabbit vascular injury model.

Conclusions

Paclitaxel-loaded NPs with DMAB modification were proven an effective means of inhibiting proliferative response to vascular injury in a rabbit model.