Liggins R T, Burt H M
Angiotech Pharmaceuticals Inc., 6660 N.W. Marine Drive, Vancouver, B.C., Canada V6T 1Z4.
Adv Drug Deliv Rev. 2002 Feb 21;54(2):191-202. doi: 10.1016/s0169-409x(02)00016-9.
A number of hypersensitivity reactions have been attributed to the presence of Cremophor((R)) EL in the current formulation for paclitaxel. This has led to the development of formulations for paclitaxel employing polyether-polyester diblock copolymers as micelle forming carriers. Diblock copolymers of methoxypolyethylene glycol-block-poly(D,L-lactide) (MePEG:PDLLA) were synthesized from monomers of D,L-lactide and MePEG by a ring opening bulk polymerization in the presence of stannous octoate. Up to 25% paclitaxel could be loaded into matrices of MePEG:PDLLA (60:40, MePEG molecular weight of 2000) using the solution casting method. Dissolution of paclitaxel/copolymer matrices in aqueous media resulted in complete solubilization of paclitaxel within the hydrophobic PDLLA core of the micelles. This review article describes the synthetic reaction conditions influencing the degree of conversion of monomer to copolymer, thermal properties, critical micelle concentrations of copolymers, methods of incorporation of paclitaxel into copolymer matrices and subsequent constitution in aqueous media and biological evaluations of micellar paclitaxel.
在目前的紫杉醇制剂中，多种超敏反应被认为与聚氧乙烯蓖麻油（克列莫佛，Cremophor((R)) EL）的存在有关。这促使人们开发以聚醚 - 聚酯二嵌段共聚物作为胶束形成载体的紫杉醇制剂。甲氧基聚乙二醇 - 聚（D，L - 丙交酯）（MePEG:PDLLA）二嵌段共聚物由D，L - 丙交酯和MePEG单体在辛酸亚锡存在下通过本体开环聚合反应合成。采用溶液浇铸法，高达25%的紫杉醇可负载到MePEG:PDLLA（60:40，MePEG分子量为2000）的基质中。紫杉醇/共聚物基质在水性介质中的溶解导致紫杉醇在胶束的疏水PDLLA核内完全溶解。这篇综述文章描述了影响单体向共聚物转化率的合成反应条件、热性能、共聚物的临界胶束浓度、将紫杉醇掺入共聚物基质的方法以及随后在水性介质中的构成和胶束紫杉醇的生物学评价。
