心血管内局部定位药物缓释体系的实验研究

Studies on Intravascular Local Drug Delivery Systems

本研究探讨了载药纳米微球(NP)作为血管内靶向定位药物控释载体的可行性,通过最佳配方和导入条件的筛选为临床研究提供了基础.用聚乳酸-乙醇酸共聚物(PLGA)制备了包载抗细胞增生药物细胞松驰素B的生物降解性纳米微球.用狗为实验动物研究了正常血液循环条件下,纳米微球在血管内的吸收和定位的可能性和最佳条件.结果表明载药纳米微球可穿透结缔组织并被靶部位的血管壁吸收,可以用介入方法将NP导入血管内病灶部位,并使其在血管局部组织内缓慢释放药物,从而维持长期局部有效药物浓度,可达到有效地治疗心血管再狭窄及其他血管疾病的目的.

Biodegradable nanoparticles (NP) could prove to be a promising dosage form for the local therapy of restenosis. In this paper,studies were carried out to understand the determinants of optimal uptake of nanoparticals by the arterial wall. Nps containing an antiproliferative agent Cy-tochalasin B were formulated from oil - water emulsion formulations ,using biodegradable polymers such as poly (lactic acid-co-glycolic acid) (PLGA). The NPS were solid sphere of 60-220nm with drug loading around 15%(w/w). No free drug crystals outside the nanoparticle body were observed by scanning electron microscopy. A new acutedog model for assessing NP uptake for the in-tra-arterial localization of therapeutic agents for inhibition of restenosis has been characterized. In general. infusions of nanoparticle suspension (15sec) resulted in 20-fold higher NP uptake levels in targeted arteries than nontargeted site. Higher concentration of NP suspension favored higher NP arterial uptake. These results support the view that nanoparticles along with optimized infusion conditions could enhance arterial wall drug concenrtations of agents to treat restenosis.