摘要
目的通过优化奥沙利铂(L-OHP)长循环脂质体的制备工艺,以提高其包封率(entrapment efficiency,EE%)并达到缓释效果。方法采用Taguchi正交法L9(34)(TOA),以包封率作为考察指标并采用超滤法检测包封率。考察了L-OHP脂质体的粒径、zeta电位、形态以及体外释放行为。结果药物与脂质间的比例(W/W),胆固醇与磷脂酰胆碱的比值(M/M)和超声时间是影响最大的三个因素(P<0.05)。此外,优化后的奥沙利铂脂质体经mPEG修饰后与未修饰的奥沙利铂脂质体相比较,具有更好的物理化学特性,其粒径为(204±1.1)nm,包封率高达25.40%±2.5%。修饰后的脂质体在透射电子显微镜下呈现球形结构,具有较大的内部空间,脂质体表面可见白色mPEG层状结构。经mPEG修饰的奥沙利铂脂质体相比于未修饰的脂质体,具有更低的体外释放速率,具有一定缓释能力。修饰与未修饰的脂质体以及奥沙利铂溶液均符合一级释放模型,拟合系数为0.990 2。结论经Taguchi正交法优化后的奥沙利铂长循环脂质体可作为一种新型的肿瘤靶向药物传递系统。
Objective To optimize the preparation parameters of oxaliplatin long circulated Liposomes for enhancing maximum entrapment efficiency（ EE% ） exerting sustained - release property. Methods Taguchi orthogonaL arrays L9 （ 34 ） （TOA） was applied in this investigation with encapsulation efficiency as an evaluation index. The entrapment efficiency was calculated using Ultra- filtration techniques. The particle size ,zeta potential and in vitro release behavior of L- OHP lipo- somes were characterized. Results The drug to lipids ratio （W/W） , the cholesterol to phosphatidylchoLine ratio （ M/M ） and the sonication time were found to be the most influencing factors （ P 〈 0.05 ）. Moreover, the optimized L - OHP mPEG - modified liposome showed better physieoehemical characteristics compared to the optimized L - OHP bare Liposomes with a smaller particle size of 204 mn and higher entrapment efficiency up to 25.4%. TEM visualization revealed spherical struc- ture with a large internal space and a white coated film surrounding the mPEG - modified liposomes. The in vitro release of L - OHP fi＇om mPEG - modified liposome was found to be slower than that of bare liposomes and L - OHP solution, respec- tively. The release profile of both liposomes and solution were well described by first order model with a coefficient correla- tion of 0.990 2. Conclusion The optimized L - OHP long circulated liposomes using TOA design may be a promising car- rier for L - OHP delivery into tumors compared to the conventional bare liposome.
出处
《药学研究》
CAS
2014年第4期187-191,195,共6页
Journal of Pharmaceutical Research
基金
国家自然科学基金(No.81201182)
中央高校基本科研业务费专项基金(No.JKPZ2013006)
