Center of Drug Metabolism and Pharmacokinetics, College of Pharmacy, China Pharmaceutical University, Nanjing, PR China.
Int J Pharm. 2012 Sep 15;434(1-2):155-60. doi: 10.1016/j.ijpharm.2012.05.041. Epub 2012 May 27.
Three most commonly used preparative methods, dry-film, reverse phase evaporation and ethanol injection were employed to prepare cationic liposomes composed of DC-Chol and DOPE, respectively. The resulting samples were contrasted through morphology observation, particle size and zeta potential analysis. Sephadex filtration method with high selectivity was developed to determine the encapsulation efficiency of plasmid DNA-loaded cationic vectors, on this basis, cationic liposomes formulation was further optimized by applying Box Behnken design with encapsulation efficiency as evaluation index. The results showed that liposomes prepared by dry-film method were of best quality and stability, moreover, the optimum formulation of cationic liposomes and optimal value of each influencing factors were quantitatively obtained, measured value was highly consistent with predicted results. These findings preliminarily clarified the effect of preparative methods on performance of cationic liposome, as well as formulation factors on encapsulation efficiency, and will provide important methodological reference for further study of liposomes carriers for gene delivery.
采用干膜法、反相蒸发法和乙醇注入法三种最常用的制备方法，分别制备了由 DC-Chol 和 DOPE 组成的阳离子脂质体。通过形态观察、粒径和 Zeta 电位分析对所得样品进行对比。开发了具有高选择性的葡聚糖凝胶过滤法来测定负载质粒 DNA 的阳离子载体的包封效率，在此基础上，以包封效率为评价指标，采用 Box-Behnken 设计进一步优化阳离子脂质体的配方。结果表明，干膜法制备的脂质体质量和稳定性最好，此外，还定量获得了阳离子脂质体的最佳配方和各影响因素的最佳值，实测值与预测结果高度一致。这些发现初步阐明了制备方法对阳离子脂质体性能的影响，以及配方因素对包封效率的影响，为进一步研究基因传递用脂质体载体提供了重要的方法学参考。
