[Surface-modified paclitaxel-loaded nanoparticles as local delivery system for the prevention of vessel restenosis].
The novel paclitaxel-loaded nanopaticle through surface modification with didodecylmethylammonium bromide (DMAB) was prepared and its prevenative against neointimal formation in a rabbit carotid artery injury model was tested. Paclitaxel-loaded nanoparticles were prepared from oil-water emulsions using biodegradable poly (lactic acid-co-glycolic acid) (PLGA). Specific additive for surface conjugation was added after particle formation. To enhance arterial retention using a cationic surfactant, DMAB, was used. The size and distribution, surface morphology and surface charge of the paclitaxel-loaded nanoparticles were then investigated by laser light scattering, scanning electron microscope and zeta potential analyzer. The drug encapsulation efficiency (EE) and in vitro release profile were measured by high-performance liquid chromatography (HPLC). Balloon injured rabbit carotid arteries were treated with single infusion of the paclitaxel-loaded NP suspension and observed for 28 days. The inhibitory effects of vascular smooth muscle cell migration and proliferation were evaluated as end-point. The NPs showed spherical shape with diameter ranging from 200 to 500 nm. The negatively charged PLGA NPs shifted to positive after the DMAB modification. The in vitro drug release profile showed a triphasic release pattern. 28 days later, morphologic analysis revealed that the inhibitory effect of intima proliferation is dose-dependent, and the 30 mg x mL(-1) nanoparticle concentration suspension could completely inhibit proliferation of intima. Paclitaxel-loaded nanoparticles through surface modification with DMAB provide an effective means of inhibiting proliferation response to vascular injury in the rabbit.
Mei
Lin
L
Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, The Tianjin Key Laboratory of Biomaterial Research, Tianjin 300192, China.
Song
Cun-Xian
CX
Jin
Xu
X
Che
Yong-Zhe
YZ
Jin
Zhe
Z
Sun
Hong-Fan
HF
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; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005260:Female; D006965:Hyperplasia / Q000517:prevention & control; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D053758:Nanoparticles; D036103:Nanotechnology; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D017539:Tunica Intima / Q000293:injuries / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017239:Paclitaxel