CAJ | 학술논문

采用改进的乳化-溶剂挥发工艺制备CsA-PLA纳米载体,以包封率为指标,用Box-Behnken法优化CsA-PLA纳米载体制备工艺.采用透射电镜、Zetasizer Nano 粒度仪评价产品的形貌、表面电位、粒径及粒径分布,在HPLC法测定CsA含量基础上,开展纳米载体体外释放特性研究.Quality by Design(QbD)预测的最佳工艺参数为PLA用量115.0 mg、CsA投药量22.2 mg、二氯甲烷3.45 mL和丙酮2.55 mL.在此条件下制备的纳米载体平均粒径为(168.7±4.3) nm,zeta电位为(?16.9±0.47) mV,载药量0.323 mg?mg?1,载体球形度和单分散性优良,药物包封率为(90.73±0.61)%,接近预测值91.05%.在符合漏槽条件的释放介质中,CsA-PLA纳米粒呈现了pH依赖型基质溶蚀缓释特征,7 d时在模拟胃、肠液中的累积释放率分别达到41.1%和80.4%.实验证明了QbD在预测制备CsA-PLA纳米载体的潜力.
채용개진적유화-용제휘발공예제비CsA-PLA납미재체,이포봉솔위지표,용Box-Behnken법우화CsA-PLA납미재체제비공예.채용투사전경、Zetasizer Nano 립도의평개산품적형모、표면전위、립경급립경분포,재HPLC법측정CsA함량기출상,개전납미재체체외석방특성연구.Quality by Design(QbD)예측적최가공예삼수위PLA용량115.0 mg、CsA투약량22.2 mg、이록갑완3.45 mL화병동2.55 mL.재차조건하제비적납미재체평균립경위(168.7±4.3) nm,zeta전위위(?16.9±0.47) mV,재약량0.323 mg?mg?1,재체구형도화단분산성우량,약물포봉솔위(90.73±0.61)%,접근예측치91.05%.재부합루조조건적석방개질중,CsA-PLA납미립정현료pH의뢰형기질용식완석특정,7 d시재모의위、장액중적루적석방솔분별체도41.1%화80.4%.실험증명료QbD재예측제비CsA-PLA납미재체적잠력.
CsA-PLA nanoparticles were prepared by modified emulsification-solvent evaporation method. The optimized formula for preparation was screened by Box-Behnken design with the entrapment efficiency as the index. The Transmission Electron Microscope and Zetasizer Nano instruments were utilized to investigate the morphology and surface potential, mean particle size and size distribution of the nanoparticles, respectively. Based on determining the content of CsA with HPLC, in vitro release behavior of CsA loaded nanoparticles were studied. Optimized parameters of CsA-PLA nanoparticles preparation predicted by Quality by Design are 115.0 mg PLA, 22.2 mg CsA, 3.45 mL ethylene chloride and 2.55 mL acetone. The nanoparticles prepared under above conditions show satisfactory monodispersity and sphericity with mean size of (168.7±4.3) nm and zeta potential of (?16.9±0.47) mV. Their mean drug loading is 0.323 mg?g-1, and the experimental value of entrapment efficiency (90.73±0.61)% is very close to the predicted value of 91.05%. Under the leaking tank condition, a kind of sustained release characteristics based on pH-dependent matrix solution was shown and cumulative release ratios of 41.1%and 80.4%in simulated gastric and intestinal media were determined at 7th day, respectively. The potential of using Quality by Design to predict and optimize the preparation parameters of CsA loaded PLA nanoparticles was experimentally proved.