全反式维甲酸-聚酸酐长效缓释剂研制及可行性分析

目的：以可生物降解高分子材料聚酸酐(Polyanhydrides，PAD) 作载体，包埋全反式维甲酸（ATRA）,研制长效缓释微球ATRA-PAD肿瘤治疗剂。建立高效液相色谱法(HPLC)测定体系,以检测缓释治疗剂中ATRA含量，探讨体内外ATRA经时缓释变化规律。方法：采用乳剂一扩散溶剂挥发法制备维甲酸长效缓释微球ATRA-PAD肿瘤治疗剂，扫描电镜检测微球外观及微球粒径，HPLC检测微球载药量、包封率及体内外释药量。结果：所制治疗剂微球光滑圆整，大小均一，平均粒径：(154．42?6.76) nm，载药率：(16.52?1.45)％，包封率：(87.84?.79)％；体外释放实验证明该微球治疗剂可持续释放ATRA约50天，将其肌肉注射到大耳白兔体内，可稳定缓释ATRA近约45天。结论：ATRA-PAD治疗剂制备工艺合理，载药量及包封率均较高，体内外释药释药平稳并且具有明显的长效缓释作用。

All-trans retinoic acid - polyanhydride long-acting release development and feasibility analysis

Objective: biodegradable Polyanhydrides (PAD) as carrier, encapsulated all-trans retinoic acid (ATRA), development of long-acting sustained-release microspheres ATRA-PAD therapeutic agent. The establishment of high performance liquid chromatography (HPLC) system for the determination to detect slow-release treatment agent ATRA levels of ATRA in vivo release by the changes of time. Methods: The proliferation of emulsion solvent evaporation a long-acting sustained-release microspheres retinoic acid ATRA-PAD therapeutic agent, scanning electron microscopy microspheres appearance and microsphere size, HPLC detection of microsphere drug loading, encapsulation efficiency and body volume of internal and external release. Results: The therapeutic system of microspheres had smooth uniform size, the average particle size: (154.42 ?26.76) nm, drug loading: (16.52 ?1.45)%, encapsulation efficiency: (87.84 ?4.79)%; release in vitro experiments indicate that the sustainable release of therapeutic agents ATRA ball about 50 days, to intramuscular injection to rabbits in vivo, ATRA may be nearly stable release of about 45 days. Conclusion: ATRA-PAD reasonable therapeutic preparation, drug loading and encapsulation efficiency were high, smooth drug release in vivo drug release and has obvious long-term sustained action.