瘤内注射用阳离子型紫杉醇乳脂体的制备及体外性质评价

Preparation and in vitro characterization of paclitaxel-loaded cationic nanoemulsomes for intratumoral drug delivery

目的:制备适于瘤内给药的阳离子型紫杉醇乳脂体(PTX-CTAB-NES),并对其理化性质及细胞毒性进行评价。方法:采用溶剂蒸发法制备PTX-CTAB-NES,利用中心复合设计优化处方,透射电镜观察形态,纳米粒径仪测定粒径分布,XRD确证PTX在载体中的分散状态,HPLC法测定其包封率、载药量,透析法研究制剂的体外释药行为,并对其细胞毒性进行评价。结果:PTX-CTAB-NES呈类球形,可见明显指纹结构,平均粒径为94.0 nm,Zeta电位为+48.3 mV,包封率、载药量分别为98.0%和3.25%,PTX在载体中以非晶型状态存在。与Taxol注射液相比,阳离子型紫杉醇乳脂体具有明显的缓释作用,对MCF-7人乳腺癌细胞的IC50降低。结论:PTX-CTAB-NES正电性强,包封率高,缓慢释放药物,细胞毒性大,是瘤内原位给药的理想载体。

Objective： To develop an appropriate nanocarrier for intratumoral drug delivery, paclitaxel loaded cationic nanoemulsomes （PTX-CTAB-NES） was prepared and investigated in vitro. Methods： PTX-CTAB- NES was prepared by solvent evaporation method. The formulation was optimized by central composite design. The morphology of PTX-CTAB-NES was observed by transmission electron microscopy （TEM）. The mean particle size and zeta potential were measured by laser particle size analyzer. The state of drug in nanoemulsomes was confirmed by X-ray diffraction （XRD）. Drug loading and encapsulation efficiency were determined by HPLC. Dialysis meth- od at 37 ~C was employed to investigate the in vitro release of PTX-CTAB-NES. In vitro cytotoxicity of PTX-CTAB- NES was evaluated in MCF-7 cells. Results： The obtained PTX-CTAB-NES was approximately spherical in shape with average particle size of 94.0 nm and zeta potential of ＋ 48.3 mV. The drug loading and encapsulation efficiency were 98.0% and 3.25% , respectively. The release of PTX-CTAB-NES was slowed down and the IC50 to MCF- 7 human breast carcinoma cells was reduced compared with taxol injection. Conclusion： PTX-CTAB-NES with high positive charge and encapsulation efficiency, slow release as well as advanced cytotoxicity would be a promising nanocarrier for intratumoral drug delivery.