细胞穿膜肽TAT和PEG共修饰的载阿霉素脂质体的制备及工艺的优化

The preparation and optimization of doxorubicin- loaded liposomes co- modified with cell penetrating peptide TAT and PEG

目的研究细胞穿膜肽TAT和聚乙二醇(PEG)共修饰载阿霉素(DOX)脂质体的制备工艺。方法采用薄膜分散-超声法制备脂质体,主动载药法包载抗肿瘤药物DOX,以包封率、粒径为主要评价指标筛选制备工艺,并初步研究其稳定性。结果载DOX脂质体的制备工艺为:总磷脂-胆固醇(65∶35),水化溶剂为300 mmmol·L-1(NH4)2SO4缓冲液,以PBS(pH7.4)为洗脱溶剂替换外水相的硫酸铵,载药温度45℃,载药时间15 min,药脂比1∶10。所制备的载DOX脂质体性质稳定,包封率均>95%,粒径约90 nm,PDI<0.2。结论成功地制备了稳定性好、包封率高的细胞穿膜肽TAT和PEG共修饰的载DOX脂质体。

OBJECTIVE To study the preparation method of doxorubicin - loaded liposomes co - modified with cell penetrating pep- tide TAT and PEG. METHODS Co - modified liposomes were prepared by thin - film method and were used to encapsulate antican- cer drug DOX, and the best encapsulation condition was evaluated with entrapment efficiency and particle diameter. Finally, the stability of the liposomes were studied. RESULTS The best preparation procedure was screened by single factor. The screening method as followed ： the lipid film was phospholipid - cholesterol （ 65 ： 35 ） and the hydration solvent was 300 mmmol · L - 1 （ NH4 ） ： S04, and the exterior（ NH4 ）2 SO4 was then replaced by PBS, the drug loading temperature was 45 ℃ , the drug loading time was 15 min, and the ratio of drug to total lipids was 1 ： 10. The liposomes were prepared following above preparation method. The partical sizes were about 90 nm with a good size distribution profile （ PDI 〈 0. 2 ） and satisfactory encapsulation efficiency （ EE 〉 95% ）. CONCLUSION Doxorubicin - loaded liposomes co - modified with cell penetrating peptide TAT and PEG were successful prepared with good stability and high entrapment efficiency.