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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。方法: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。采用乳剂-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,用激光散射粒度测定仪进行粒径检测,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±26.76)μm,载药率:(16.52±1.45)%,包封率:(87.84±4.79)%;体外释放试验证明该微球治疗剂可持续释放ATRA约50 d,将其采用肌内注射法注入到大耳白兔体内,可稳定缓释ATRA近约45 d。结论:ATRA-PAD治疗剂体内外释药释药平稳,并且具有明显的长效缓释作用。
OBJECTIVE: To prepare a long-acting sustained-release microspheres ATRA-PAD tumor therapeutic agent by using polyanhydrides (PAD) as a carrier and embedding all-trans retinoic acid (ATRA). Methods: A high performance liquid chromatography (HPLC) system was established to detect the content of ATRA in sustained-release therapeutic agents and to study the regularity of ATRA in vitro and in vivo. ATRA-PAD tumor therapeutic agent was prepared by emulsion-diffusion solvent evaporation method. The particle size was measured by laser scattering particle size analyzer. The drug loading, entrapment efficiency and drug release in vitro and in vivo the amount. Results: The prepared microspheres were smooth and uniform with average size of (154.42 ± 26.76) μm and drug loading rate of (16.52 ± 1.45)% and encapsulation efficiency of (87.84 ± 4.79)%, respectively. Experiments show that the microspheres therapeutic agent sustained release of ATRA for about 50 d, the use of intramuscular injection into the large white rabbits, sustained and stable release of ATRA nearly 45 d. CONCLUSION: ATRA-PAD has a stable and sustained drug release both in vitro and in vivo and has a long-term sustained release effect.