用于肿瘤光动力治疗的血卟啉单甲醚微纳米载药系统的研制

Micro-nano Particle System Loaded with HMME for Tumor Photodynamic Therapy

目的：用侧基含羧基的聚-L-丙交酯-co-3-羧甲基-吗啉-2,5-二酮（P-LLA-co-Asp）两亲性共聚物为载体,制备含血卟啉单甲醚（HMME）和微纳米粒子,初步考察不同共聚组成聚合物制得的微纳米粒性能及体外释放行为,探讨HMME微纳米粒的靶向光动力治疗可行性。方法：用不同共聚组成比的P-LLA-co-Asp,采用改进的溶剂挥发法制备含HMME的微纳米粒子,表征微纳米粒子的粒径大小及分布、表面形态,检测HMME在微纳米粒形成前后荧光激发性能及其激发三线态寿命,考察微纳米粒子体外释放行为的差异。结果：制得了粒径均匀,分布较窄,范围在400~700nm,表面平整光滑的含HMME微纳米粒子;共聚物制得微纳米粒中载药量和包封率明显高于PL-LA均聚物,并随材料亲水性共聚组成（Asp）的增加而增加;微纳米粒体系中HMME结构及其荧光激发性能没有改变,能够被激发成三线态,并具有相应的寿命时间;共聚物形成微纳米粒的HMME释放速率低于PLLA均聚物释放速率。结论：①不同的共聚组成对微纳米粒子的性能和释放行为有很大的影响,推测可能是由于HMME与共聚物的羧基之间形成了氢键的相互作用有关。②该共聚物体系作为HMME的微纳米粒子载体,保持了其作为光敏剂的结构和性能,有望应用对该微纳米粒子进一步进行肿瘤的靶向光动力治疗的研究。

Objective： To explore the feasibility of hematoporphyrin monomethyl ether（HMME） used in tumor target photodynamic therapy（PDT）, and the micro-nano particles of poly（K-lactide-co-3-carboxymethyl-morpho-line-2,5-dione）（P-LLA-co-Asp） loaded with HMME were prepared and characterized. Methods： P-LLA-co-Asp micro-nano particles loaded with HMME were prepared by using improved solvent evaporation method（O/W）. Particle size and size distribution and surface morphology were characterized. The fluorescence excitation property and triplet state longevity of HMME loaded in micro-nano particles were compared with unloaded HMME. The differences of in vitro HMME release behavior from micro-nano particles prepared with different molar ratio of P-LLA-co-Asp were also evaluated. Results： HMME loaded micro-nano particles at the range of 400-700nm with regular size and narrow size distribution and smooth surface were obtained. The drug loading and loading efficiency of HMME in P-LLA-co-Asp particles were enhanced obviously than poly-l-lactide（PLLA）, and the more the aspartic acid（Asp） content was, the higher the drug loading and loading efficiency was showed. The structure of HMME and its properties as photosensitizer were not destroyed in the process of particle formation. The HMME in the particles can be excited to triplet state with proper longevity time. The release behaviors of HMME were influenced by the molar ratio of LLA and Asp. Conclusion： ①The property and release behavior of micro-nano particles are affected apparently by the molar ratio of LLA and Asp. ②The photosencitizer property and structure are maintained of HMME in the micro-nano particle system, so it is worthy to make further study on the HMME micro-nano particle system used in tumor target PDT.