载药纳米载体联合光敏剂的淋巴靶向性研究

Lymphatic target of nanometer with photodynamic therapy

目的:探讨纳米载体(PBCA-NP)联合光敏剂(HMME)应用于家兔腹腔淋巴结组织的淋巴靶向性研究。方法:制备血卟啉单甲醚-聚氰基丙烯酸正丁酯纳米载体(HMME-PBCA-NP)并检测纳米粒的理化性质和体外释放情况;将家兔随机分为两组,分别给予腹腔注射相同剂量HMME-DMSO和HMME-PBCA-NP溶液,检测血浆中HMME含量得到血卟啉单甲醚的药物代谢动力学参数,于不同时间点处死家兔,检测不同组织中的HMME含量,得到血卟啉单甲醚的组织药物分布。结果:成功制备出HMME-PBCA-NP纳米胶束,粒径为160nm左右,包封率为87.9%,载药量为13.4%;与单纯血卟啉单甲醚溶液组相比,纳米组家兔血清及组织到达药物峰浓度时间均向后推迟(6h vs 3h);腹腔注射不同剂型药物6h后,药物浓度在家兔肠系膜淋巴组织中的差值达到最大[(1.2884±0.04695)μg/ml vs(0.0438±0.00558)μg/ml],肉眼观察,纳米载体组家兔肠系膜淋巴结明显肿大。结论:纳米粒经过腹腔注射具有缓释作用;载药纳米载体经过腹腔注射途径具有淋巴靶向性作用。

Objective： To investigate the lymphatic targeting to rabbit celiac lymph node tissue using poly（ n-butylcyanoacrylate） nanoparticle（ PBCA-NP） with photosensitizer hematoporphyrin monomethyl ether（ HMME） by intraperitoneal injection. Methods： The HMME-PBCA-NP was prepared,and its physical and chemical properties were tested. Rabbits were randomly divided into two groups; animals in group A received intraperitoneal injection HMME-dimethyl sulfoxide（ DMSO） solution,whereas rabbits in group B received intraperitoneal injection in the same dose of HMME-PBCA-NP solution. The pharmacodynamic characteristics and biodistribution of different groups were evaluated by the HPLC technology. Results：HMME-PBCA-NP was formed successfully.The particle size was 160±13.7nm.The envelopment rate was 87.9%,and the drug-loading rate was 13.4%.Compared with the HMME-DMSO group,the HMME-PBCA- NP group exhibited delayed time of the peak drug concentration of plasma and tissue samples in rabbits（ 6h versus 3h）. In rabbit mesenteric lymphatic organization,the drug concentrations of experimental group B were higher than those of group A.After abdominal cavity injection for 6 h,the maximum difference of the HMME content in lymph node appeared（ 1.2884±0.04695μg /ml versus 0.0438±0.00558μg /ml）.The rabbit mesenteric lymph nodes enlarged obviously after the drug administration in group B.Conclusion： Nanotechnology has an enhanced permeability and retention（ EPR） effect,and the drug-loading nanoparticle carrier system presents a lymphatic targeting effect.