摘要
目的制备一种包载多西他赛的聚乳酸羟基乙酸-聚乙二醇-聚乳酸羟基乙酸(PLGA-PEG-PLGA)三嵌段共聚物纳米胶束,并考察其相关性能。方法采用开环聚合法合成共聚物,直接溶解法制备载多西他赛共聚物纳米胶束,荧光光谱法测定临界胶束浓度,高效液相色谱检测载药胶束的包封率与载药率,透析法测定载药胶束体外释放情况,扫描电镜观察纳米胶束的形态,激光粒径仪测量共聚物纳米胶束粒径及分布,改良寇氏法测定载药胶束的半数致死量。结果直接溶解法制备的共聚物纳米胶束的临界胶束浓度为4.5×10-3 g/L,多西他赛与共聚物投料比为1∶20制备的载多西他赛共聚物纳米胶束的包封率为98.20%,载药率达4.68%,在体外平稳释放时间约3 d。扫描电子显微镜观察载多西他赛共聚物纳米胶束呈类圆形,分散良好,平均粒径为30.8 nm,多元分散系数0.42。载多西他赛共聚物纳米胶束静脉注射小鼠的半数致死量为273.5 mg/kg。结论采用直接溶解法可制备一种载多西他赛的PLGA-PEG-PLGA三嵌段共聚物纳米胶束,包封率高,体外释药平稳,毒副作用小,具有潜在的临床应用价值。
Objective To investigate the preparation and characterization of docetaxel-loaded block copolymer micelles.Methods The tri-block copolymer poly（lactic-co-glycolic acid）-poly（ethylene glycol）-poly（lactic-co-glycolic acid）（PLGA-PEG-PLGA） was synthesized by ring-opening polymerization process,and the docetaxel-loaded micelles were prepared using direct dissolution method.The critical micelle concentration was measured by pyrenemonomer fluorescence probe technology;the encapsulation efficiency,loading rate,and in vitro release were determined by high-performance liquid chromatography（HPLC）.The morphology and size of micelles were observed with scanning electron microscope and laser light particle size detector,respectively.The 50 % lethal dose of docetaxel-loaded micelles in mice was calculated by modified Kaber method.Results The critical micelle concentration was 4.5 × 10-3 g/L.The prepared docetaxel-loaded micelles had a spherical geometry with a median size of 30.8 nm,and the micelles possessed an eligible loading rate and encapsulation efficiency of 4.68 % and 98.20 % respectively as detected by HPLC.The in vitro release profile of docetaxel from micelles showed the continuous drug release of 3 days.The 50 % lethal dose of docetaxel-loaded micelle in mice was increased to 273.5 mg/kg,which was about 6 times higher than that of docetaxel.Conclusion It is demonstrated that the prepared docetaxel-loaded block copolymer micelles possess high drug encapsulation efficiency,stable in vitro drug release and low systemic toxicity,which has potential clinical value.
出处
《生物医学工程与临床》
CAS
2011年第2期99-102,共4页
Biomedical Engineering and Clinical Medicine
基金
福建省自然科学基金(2009J05066)
关键词
多西他赛
聚合物
胶束
缓释材料
纳米粒子
聚乳酸羟基乙酸
聚乙二醇
docetaxel
copolymer
micelle
sustained-release material
nanoparticles
poly（lactic-co-glycolic acid）
poly（ethylene glycol）
