Aliabadi Hamidreza Montazeri, Elhasi Sara, Mahmud Abdullah, Gulamhusein Rashida, Mahdipoor Parvin, Lavasanifar Afsaneh
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2N8, Canada.
Int J Pharm. 2007 Feb 1;329(1-2):158-65. doi: 10.1016/j.ijpharm.2006.08.018. Epub 2006 Aug 22.
This study was designed to develop an optimized co-solvent evaporation procedure for the efficient encapsulation of hydrophobic drugs in polymeric micelles of methoxy poly(ethylene oxide)-block-poly(epsilon-caprolactone) (MePEO-b-PCL). MePEO-b-PCL block copolymers having varied MePEO and PCL molecular weights were synthesized, assembled to polymeric micelles, and used for the encapsulation of cyclosporine A (CyA) by a co-solvent evaporation method. The co-solvent composition was varied by changing the type of organic co-solvent (using acetone, acetonitrile and tetrahydrofuran), the ratio of organic to aqueous phase, and their order of addition. Carrier size, morphology and encapsulated CyA levels were defined by dynamic light scattering (DLS), transmission electron microscopy (TEM) and HPLC, respectively, and the effect of co-solvent composition on micellar properties and loaded CyA levels was evaluated. Application of acetone and acetonitrile as the selective co-solvent for the core-forming block led to a decrease in the average diameter of self-assembled structures. When acetone was added to water, a decrease in the ratio of organic to aqueous phase led to an increase in the loading efficiency of CyA in MePEO-b-PCL micelles. A similar trend in CyA loading was observed for MePEO-b-PCL micelles of varied MePEO and PCL block lengths. The ratio of organic to aqueous phase did not affect CyA loading when water was added to acetone. Irrespective of the order of addition, the decrease in the organic to aqueous phase ratio caused a reduction in the average diameter of the empty and CyA loaded micelles. We conclude that the co-solvent evaporation method may be optimized to improve the efficiency of drug encapsulation in polymeric micelles. For CyA encapsulation in MePEO-b-PCL micelles, addition of acetone to water at lower organic to aqueous phase ratio is shown to be the optimum procedure leading to higher drug encapsulation and smaller average diameter for the self-assembled structures.
本研究旨在开发一种优化的共溶剂蒸发程序，以有效地将疏水性药物包封于甲氧基聚（环氧乙烷）-嵌段-聚（ε-己内酯）（MePEO-b-PCL）的聚合物胶束中。合成了具有不同MePEO和PCL分子量的MePEO-b-PCL嵌段共聚物，将其组装成聚合物胶束，并通过共溶剂蒸发法用于包封环孢素A（CyA）。通过改变有机共溶剂的类型（使用丙酮、乙腈和四氢呋喃）、有机相与水相的比例及其添加顺序来改变共溶剂组成。分别通过动态光散射（DLS）、透射电子显微镜（TEM）和高效液相色谱（HPLC）确定载体尺寸、形态和包封的CyA水平，并评估共溶剂组成对胶束性质和负载CyA水平的影响。使用丙酮和乙腈作为形成核的嵌段的选择性共溶剂导致自组装结构的平均直径减小。当将丙酮加入水中时，有机相与水相比例的降低导致CyA在MePEO-b-PCL胶束中的负载效率增加。对于不同MePEO和PCL嵌段长度的MePEO-b-PCL胶束，观察到CyA负载有类似趋势。当将水加入丙酮中时，有机相与水相比例不影响CyA负载。无论添加顺序如何，有机相与水相比例的降低都会导致空胶束和负载CyA的胶束的平均直径减小。我们得出结论，共溶剂蒸发法可进行优化以提高药物在聚合物胶束中的包封效率。对于将CyA包封于MePEO-b-PCL胶束中，在较低有机相与水相比例下将丙酮加入水中被证明是最佳程序，可导致更高的药物包封率和自组装结构的更小平均直径。
