多西紫杉醇胶束的制备及其肿瘤球穿透行为的研究

Preparation of docetaxel-loaded micelles and its tumor penetration behaviors

目的制备多西紫杉醇(DTX)胶束,考察DSPE-PEG2000对胶束形态,包封率,释放和肿瘤球穿透行为的影响。方法以DPPC/DSPE-PEG2000为处方组成,采用薄膜水合法制备纳米载体,通过透射电子显微镜考察DSPE-PEG2000含量对纳米载体形态的影响;筛选球状胶束处方,制备DTX胶束,微柱离心法测定包封率,粒度分析仪对粒径进行表征,透析法考察其体外释放行为;以香豆素-6(Coumarin-6,C6)代替药物,通过激光共聚焦显微镜观察其在4T1肿瘤球中的穿透行为。结果含10mol%和14 mol%DSPE-PEG2000时,形成球状胶束;含10 mol%DSPE-PEG2000的球状胶束粒径为(42.50±0.60)nm,PDI为(0.127±0.015),包封率大于95%,24 h时制剂的累积释放百分数低于30%;含10 mol%DSPE-PEG2000的C6球状胶束在肿瘤球中穿透较快。结论 DSPE-PEG2000含量会影响胶束形态,脂溶性药物的包封率以及在肿瘤球中的穿透行为。

Objective To prepare the docetaxel （DTX）-loaded micelles and to evaluate properties such as entrapment efficiency, in vitro release and penetration in 4T l tumor spheres. Methods The shape of nanoearriers containing different DSPE-PEG2000 content was observed by transmission electron microscopy. DTX-loaded mixed micelles were prepared by thin-film hydration method, and EE% was determined by the mini-column centrifugation method. The particle size and PDI of DTX-loaded mixed smicelles were measured by dynamic light scattering. The in vitro release behaviors of DTX-loaded mixed micelles were determined by the dialysis method. Besides, coumarin-6 （C6） was used as the model drug and the penetration in 4T1 tumor spheres was observed by confocal laser scanning microscope. Results Spherical micelles were formed in 10 mol% and 14 mol% DSPE- PEG2000. DTX-loaded mixed miceUes of 10 mol% DSPE-PEG2000 showed better properties, with a particle size of （42.50± 0.60） nm, PDI of （0.127 ±0.015） and EE% of more than 95%, with the 24 h accumulated release ratio in vitro less than 30%. The C6-1oaded spherical micelles penetrated faster in 4T1 tumor spheres. Conclusion The shape, EE% of lipophilic drugs and penetration in 4T1 tumor spheres are affected by DSPE-PEG2000 content.