Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Mohali 160062, Punjab, India.
Mol Pharm. 2011 Apr 4;8(2):466-78. doi: 10.1021/mp1003256. Epub 2011 Feb 23.
This study is focused on the preparation of doxorubicin-loaded nanopolymersomes (PolyDoxSome) and assessment of the effects of various solvents and process variables on the size and drug loading during preparation of formulation. PolyDoxSome was prepared by nanoprecipitation method using amphiphilic (PEG)₃-PLA copolymer, and the formation of polymersomes was assessed by dynamic light scattering and optical and transmission electron microscopy and evaluated for in vitro release profile and in vitro cytotoxicity. A systematic investigation indicated that solvent composition, order of addition, aqueous phase, copolymer concentration, and external energy input have significant influence on size and dispersity of PolyDoxSome. Under optimized conditions, PolyDoxSome had a size range of 130-180 nm with PDI < 0.2, a zeta potential ∼-8 mV, and a drug loading at ∼11% w/w with an encapsulation efficiency at ∼53% w/w. In vitro release profile of PolyDoxSome at 37 °C demonstrated that doxorubicin release was pH dependent and gave higher release at pH 5.5 in comparison to the release at pH 7.4 (similarity factor, f₂ < 50). PolyDoxSome exhibited enhanced cellular uptake of doxorubicin compared to free doxorubicin solution in MCF-7 cell line and showed a better cytotoxicity of doxorubicin at equivalent dose in nanopolymersomes. In conclusion, size and dispersity were strongly influenced by duration of magnetic stirring and overall composition of organic/aqueous media; however, size and dispersity were retained against different degrees of dilution. PolyDoxSome was able to control the release of doxorubicin in pH dependent manner and effectively deliver the drug in active form to MCF-7 breast cancer cells.
这项研究专注于制备多柔比星负载的纳米聚合物囊泡（PolyDoxSome），并评估在制剂制备过程中，不同溶剂和工艺变量对粒径和药物载量的影响。PolyDoxSome 通过两亲性（PEG）₃-PLA 共聚物的纳米沉淀法制备，并通过动态光散射、光学和透射电子显微镜评估聚合物囊泡的形成情况，并对体外释放曲线和体外细胞毒性进行评价。系统研究表明，溶剂组成、添加顺序、水相、共聚物浓度和外部能量输入对 PolyDoxSome 的粒径和分散性有显著影响。在优化条件下，PolyDoxSome 的粒径范围为 130-180nm，PDI<0.2，zeta 电位约为-8mV，药物载量约为 11%w/w，包封效率约为 53%w/w。在 37°C 下，PolyDoxSome 的体外释放曲线表明，多柔比星的释放依赖于 pH 值，在 pH 5.5 时的释放量高于在 pH 7.4 时的释放量（相似因子 f₂<50）。与游离多柔比星溶液相比，PolyDoxSome 在 MCF-7 细胞系中表现出更高的多柔比星细胞摄取能力，并在纳米聚合物囊泡中以等效剂量表现出更好的多柔比星细胞毒性。总之，尺寸和分散性受磁场搅拌时间和有机/水介质总体组成的强烈影响；然而，在不同程度的稀释下，尺寸和分散性仍能保持。PolyDoxSome 能够以 pH 依赖的方式控制多柔比星的释放，并将药物以有效形式递送至 MCF-7 乳腺癌细胞。
