磷酸壳寡糖修饰阿霉素脂质体的制备及体内外评价

Prepration and Evaluation of Phosphorylated Chitooligosaccharide Modified Doxorubicin Liposome in vitro and in vivo

本研究首次合成了磷酸壳寡糖-胆固醇接枝物(PCS-Chol),并对其结构、取代度和特性黏度等进行了考察.制备了由该接枝物所修饰的磷酸壳寡糖-阿霉素脂质体(PCS-DOX-L),考察了该脂质体的粒径、包封率、形态以及体外释放.采用MTT法评价了该制剂对MG63细胞的毒性,并进一步研究了其在荷瘤裸鼠体内的组织分布情况.结果表明,该脂质体的粒径为209.5 ± 0.5 nm,包封率为(85.4 ± 2.2)%;体外释放具有一定的pH响应性和缓释特性.MTT实验表明该脂质体对MG63细胞的毒性具有时间和浓度双依赖性.荷瘤裸鼠的体内分布实验表明,PCS-L具有一定的骨肉瘤靶向性.本研究初步证明了PCS在体内具有良好的骨靶向性,所修饰形成的PCS-L可用于骨肉瘤的靶向治疗.

Phosphorylated chitooligosaccharide-cholesterol graft polymer (PCS-Chol) is synthesized for the first time, and its structure, degree of substitution (DS) and intrinsic viscosity are characterized. The graft modified doxorubicin liposome (PCS-DOX-L) is prepared, and the characterizations, such as particle size, entrapment efficiency (EE), morphology and in vitro release, are investigated. The cytotoxicity to MG63 cells is evaluated by MTT assay and its tissue distribution in tumor-bearing nude mice is studied. The results show that the average particle size of the liposome is 209.5 ± 0.5 nm, the EE is (85.4 ± 2.2)%. The in vitro release shows PCS-DOX-L has a profile of pH responsiveness and sustained release. MTT assay shows that the liposome can inhibit the proliferation of MG63 cells in a manner of time-and concentration-dependent. In vivo experiment with tumor-bearing nude mice shows that PCS-L appears osteosarcoma-bearing bone targeting. In this study, PCS is used in drug carrier for the first time, which preliminarily proves that PCS has good bone targeting ability in vivo , and PCS-modified liposome can be used for targeted therapy of osteosarcoma.