摘要
目的利用聚己内酯(PCL)与亲水性添加剂泊洛沙姆188(F68)共混物作为载体材料与抗癌药物紫杉醇组成纳米粒缓释载药系统,并评价其在裸鼠人乳腺癌B37实体瘤模型中的抗肿瘤效果。方法采用超声乳化/溶剂挥发法制备紫杉醇PCL/F68载药纳米粒;对紫杉醇PCL/F68载药纳米粒进行表征及高压液相色谱法(HPLC)测定包封率和体外释放度;利用差示扫描热分析(DSC)法分析紫杉醇在PCL/F68载药纳米粒中的分散状态;评价紫杉醇PCL/F68载药纳米粒在裸鼠人乳腺癌B37实体瘤模型中的抗肿瘤活性。结果紫杉醇PCL/F68载药纳米粒呈现规整的球形;平均粒径为150.50nm(标准差25.41nm),多分散系数为0.18。紫杉醇PCL/F68纳米粒的载药量为18%,药物包封率为84.36%。紫杉醇PCL/F68载药纳米粒体外药物释放研究表明在50d的释放周期内累计释放量约为49%,接近零级释放(R=0.998)。体内抗肿瘤活性实验研究表明,紫杉醇PCL/F68载药纳米粒对裸鼠人乳腺癌B37实体瘤生长具有明显抑制作用。结论肿瘤局部注射紫杉醇PCL/F68载药纳米粒能够有效地抑制肿瘤的生长。
Objective To prepare paclitaxel-loaded poly（e-caprolactone） （PCL）/poloxamer 188（F68） nanoparticle, and assess its antitumor activity in a murine breast cancer model. Methods Paclitaxel-loaded PCL/F68 nanoparticles were prepared by selfsynthesized PCL/F68 compound with the oil-in water emulsion/solvents evaporation method. Characterization of the prepared nanoparticles was observed. Its encapsulation rate and in vitro release were detected by high-pressure liquid chromatography （HPLC）. The distribution pattern of paclitaxel in PCL/F68 loaded nanoparticles was analyzed by differential scanning calorimetery （DSC） method. The in vivo antitumor activity of paelitaxel-loaded PCL/F68 nanoparticles in BALB/c nude mice models bearing human breast cancer B37 xenograft was evaluated. Results Paclitaxel-loaded nanopartieles were found as spherical shape with the average particle diameter of 150.50 nm and polydispersity coefficient of 0.18. The in vitro drug release profile showed a zero order release pattern. In vivo study was demonstrated that the effect of a single intratumoral injection with paelitaxel-loaded PCL/ F68 nanoparticles administered was superior to the same equivalent paelitaxel dose in impeding tumor development than conventional paelitaxel injections administered by multiple intraperitoneal injection in a murine breast cancer model when compared with saline group. Conclusion Intratumoral delivery of paclitaxel-loaded PCL/F68 nanoparticles has proved to be an effective approach for inhibiting the tumor cell growth.
出处
《生物医学工程与临床》
CAS
2009年第6期481-485,共5页
Biomedical Engineering and Clinical Medicine
基金
天津市自然科学基金(07JCYBJC01500)
