PLGA-PEG-PLGA温敏水凝胶包载多柔比星脂质体用于治疗小鼠骨肉瘤的研究  

Liposomal Doxorubicin Loaded PLGA-PEG-PLGA for the Treatment of Osteosarcoma

作　　者：梁国辉[1] 马琨[1] 谢艳[1] 范永春[2] 赵呈雷[2] LIANG Guo-hui;MA Kun;XIE Yan;FAN Yong-chun;ZHAO Cheng-lei(Luoyang Orthopedic-Traumatological Hospital of Henan Province,Luoyang 471002,China;Jiangsu Province Academy of Traditional Chinese medicine,Nanjing 210028,China)

机构地区：[1]河南省洛阳正骨医院,河南洛阳471002 [2]江苏省中医药研究院,南京210028

出　　处：《中国药学杂志》2022年第14期1179-1185,共7页Chinese Pharmaceutical Journal

基　　金：河南省中医药科学研究专项课题(2019ZY1035)。

摘　　要：目的 制备聚乳酸乙醇酸-聚乙二醇-聚乳酸乙醇酸共聚物(PLGA-PEG-PLGA)水凝胶包载的多柔比星(Doxorubicin,DOX)脂质体的复合载体,并考察其体外性质和抑瘤效果。方法 采用水化薄膜法制备DOX脂质体,考察其粒径分布和包封率,再利用PLGA-PEG-PLGA水凝胶包载制备得到的DOX脂质体得到DOX-Lip-Gel复合载体,考察其体外释放、黏性测试以及对荷瘤小鼠的治疗效果。结果 制备得到的DOX-Lip的粒径约为(89.3±4.7) nm,包封率约为(85.3±2.6)%,PLGA-PEG-PLGA水凝胶在25℃处于溶液状态,而在37℃时可凝固成胶,黏性测试结果表明水凝胶的相变温度约为30℃。并且水凝胶聚合物具有良好的生物相容性,在体内可以缓慢的降解。与对照组相比,DOX-Lip-Gel可以缓慢的释放药物,且释放期长达200 h。体内抑瘤实验表明DOX-Lip-Gel具有更好的抗肿瘤效果。结论 制备得到的DOX-Lip-Gel对荷瘤小鼠进行瘤周给药,对抑制骨肉瘤在小鼠体内的增长具有显著的抑制作用。OBJECTIVE To prepare the hybrid system of liposomal doxorubicin(DOX-Lip) loaded thermogel(DOX-Lip-Gel) and investigate the in vitro properties and antitumor effect.METHODS Doxorubicin liposomes were prepared by hydration membrane method.Their particle size distribution and entrapment efficiency were investigated.And the in vitro release,viscosity measurement and the anti-tumor efficiency of DOX-Lip-Gel were also investigated.RESULTS The DOX-Lip was prepared with the particle size of(89.3±4.7) nm and the drug entrapment efficiency of(85.3±2.6)%,the liposomes loaded hydrogel was in a sol state at 25 ℃ and converted into the gel state at 37 ℃ with the phase transition temperature of 30 ℃ and could degrade gradually during the time in vivo.The DOX release out of DOX-Lip-Gel could be in a sustained manner up to 200 h with no burst release.An orthotopic osteosarcoma model was adopted and the results revealed that DOX-Lip-Gel had the better antitumor efficiency.CONCLUSION DOX-Lip-Gel could significantly inhibit the growth of osteosarcoma in mice orthotopic model.

关 键 词：骨肉瘤 水凝胶 脂质体 复合载体 多柔比星 

分 类 号：R944[医药卫生—药剂学] R965[医药卫生—药学]