紫杉醇纳米粒子制备及血管内局部灌注后的组织分布

目的 制备紫杉醇纳米粒子,并考察其在实验兔体内经DispatchTM球囊灌注后组织分布情况.方法 以生物可降解材料聚乳酸聚乙醇酸共聚物(PLGA)为原料,采用超声乳化-溶剂挥发法制备载紫杉醇纳米粒子.对纳米粒子的粒径、形态、药物含量和体内外释放进行测定.通过新西兰兔腹主动脉局部给药模型考察紫杉醇纳米粒子球囊灌注后组织分布情况.结果 制备的紫杉醇纳米粒子的平均粒径约为246 nm,包封率为93.25％,紫杉醇含量19.06％.体外可维持恒定释放30d以上.新西兰兔体内经腹主动脉实现DispatchTM球囊灌注,观察药物可在靶部位体内贮留长达21d.结论 紫杉醇PLGA纳米粒子作为一种局部药物传递系统,经球囊灌注在动物模型体内提高局部药物浓度,延长药物作用时间,可实现缓释靶向治疗.

Preparation and biodistribution of paclitaxel-loaded nanoparticles after intravascular infusion

Objective To prepare paclitaxel-loaded nanoparticles （NPs）, and to observe drug biodis- tribution after intravascular infusion of the NPs using a DispatchTM catheter into New Zealand rabbit abdominal aorta models. Methods Paclitaxel -loaded NPs were prepared by uhrasonication/emulsificcation/solvent evaporation technique using biodegradable poly （lactic-co-glycolic acid）（PLGA） as drug carrier. NP size and morphology was assessed by submicro-laser defractometer and scanning electron microscopy. In vitro release of paclitaxel from the NPs was performed by shaking in PBS at 37 ℃. The NPs was delivered into New Zealand rabbit abdominal aorta using a DispatchTM catheter. Results The diameter of paclitaxel NPs was around 246 nm with very narrow size distribution. The NPs showed good spherical shape with smooth uniform surface. Paclitaxel loading in the NPs was about 19.06% with encapsulation efficiency about 93.25%. The NPs maintained a sustained in vitro drug release for 30 days in PBS. After in vivo NP infusion, paclitaxel was detected in the vascular tissue around the infusion site and it retained in the site for 21 days. Conclusion PLGA nanoparticles as local drug delivery carrier showed great potential to maintain a high local drug concentration and prolonged drug resident time in animal model in vivo.