Modified paclitaxel-loaded nanoparticles for inhibition of hyperplasia in a rabbit arterial balloon injury model.
OBJECTIVE
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.


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.
Mei
Lin
L
The Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin, 300192, China.
Sun
Hongfan
H
Jin
Xu
X
Zhu
Dunwan
D
Sun
Rui
R
Zhang
Minfang
M
Song
Cunxian
C
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D020212:Carotid Artery Injuries / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D002404:Catheterization / Q000009:adverse effects* / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D006965:Hyperplasia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D010316:Particle Size; D011098:Polyglactin 910 / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011817:Rabbits; D012995:Solubility; D013997:Time Factors; D016896:Treatment Outcome; D017539:Tunica Intima / Q000187:drug effects / Q000293:injuries / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; D011098:Polyglactin 910; D011142:Polyvinyl Alcohol; D017239:Paclitaxel