摘要
目的制备人血清白蛋白(human serum albumin, HSA)修饰的盐酸伊立替康(irinotecan hydrochloride, CPT-11)聚乳酸-羟基乙酸共聚物纳米粒(HSA/PLGA/CPT-11 NPs),对处方进行优化,对制剂进行质量评价,并初步考察其体外抗肿瘤活性。方法采用乳化-溶剂蒸发法制备HSA/PLGA/CPT-11 NPs,响应面Box-Behnken Design筛选最优处方,并制成冻干粉末。采用激光粒度仪、透射电镜、傅里叶红外光谱(fourier transform infrared spectrometer, FTIR)考察该制剂冻干粉的理化性质,采用透析法考察其体外释放规律,在低温和常温条件下考察其初步稳定性,通过细胞毒性实验初步考察其体外抗肿瘤活性。结果按优化条件制备的HSA/PLGA/CPT-11 NPs冻干粉呈球形,分布均匀,平均粒径为(98.73±2.04) nm,多分散系数(polydispersity index, PDI)为(0.257±0.03),Zeta电位为(-18.30±0.14) mV,包封率为(64.61±0.29)%。FTIR结果表明,CPT-11被纳米载体包埋后形成了新的物相。体外释放结果显示HSA/PLGA/CPT-11 NPs在24 h时释药80%。初步稳定性试验结果表明HSA/PLGA/CPT-11 NPs冻干粉在4℃和25℃条件下放置的60 d内具有良好的稳定性。溶血性实验表明,载体材料安全无毒,制备的HSA/PLGA/CPT-11 NPs冻干制剂适宜静脉注射给药。细胞学实验表明,与游离的CPT-11原料药相比,HSA/PLGA/CPT-11 NPs对人结肠癌HCT-116细胞具有增强的细胞毒性。结论采用乳化-溶剂蒸发法制备的HSA/PLGA/CPT-11 NPs粒径较小,分布均匀,包封率高,具有明显的药物缓释作用和增强的细胞毒性。
OBJECTIVE To enhance the therapeutic effects in colon cancer, the human serum albumin modified irinotecan hydrochloride PLGA nanoparticles(HSA/PLGA/CPT-11 NPs) were prepared based on the optimized prescription. Then, its pharmaceutical property and anti-tumor activity were evaluated. METHODS The HSA/PLGA/CPT-11 NPs were prepared by emulsification-solvent evaporation method, finally made into freeze-dried powder. The response surface method of Box-Behnken Design was used to optimize the initial prescription. The particle size and distribution were measured by Malvern laser granulometer. Transmission electron microscope(TEM) and Fourier transform infrared spectrometer(FTIR) were used to determine the morphology of nanoparticles and the chemical stability of CPT-11, respectively. The in vitro release behavior was determined by dialysis. The preliminary stability was studied at low temperature and room temperature, respectively. Cytotoxicity assay was employed to evaluate the anti-tumor activity of the prepared NPs. RESULTS The TEM images showed that the optimized freeze-dried HSA/PLGA/CPT-11 NPs were spherical in shape, and exhibited good dispersibility. The average particle size of HSA/PLGA/CPT-11 NPs was 98.73±2.04 nm with a polydispersity index(PDI) of 0.257±0.03, and the zeta potential was-18.30±0.14 mV. The encapsulation efficiency of CPT-11 loaded into HSA/PLGA/CPT-11 NPs was 64.61±0.29%. The results of FTIR showed that CPT-11 was embedded in the nanocarrier and formed a new phase, not a simple physical mixture. The in vitro drug release rate of HSA/PLGA/CPT-11 NPs in 24 h reached 80%. The preliminary stability test demonstrated the good stability of freeze-dried HSA/PLGA/CPT-11 NPs under 4 ℃ and 25 ℃ during 60 days, respectively. The hemolytic test shows that the carrier material is safe and non-toxic, and the prepared HSA/PLGA/CPT-11 NPs freeze-dried preparation is suitable for intravenous injection. The cytotoxicity of HSA/PLGA/CPT-11 NPs on HCT-116 cells(human colon cancer cells) was significantly
作者
刘喜阳
罗玉莹
邓盛齐
郑林
沈雪
LIU Xi-yang;LUO Yu-ying;DENG Sheng-qiu;ZHENG Lin;SHEN Xue(Antibiotics Researchand Rerraluation Key Iaboratory of Sichuan Prowince,Chengidu University,Chengdu 610106,China;Sichuan Industrial lnstitute of Antibiotics,Chengidu University,Chengdu 610106,China;School of Pharmacy,Chengidu University,Chengdu 610106,China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2021年第21期1740-1748,共9页
Chinese Pharmaceutical Journal
