Savić Radoslav, Eisenberg Adi, Maysinger Dusica
Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada.
J Drug Target. 2006 Jul;14(6):343-55. doi: 10.1080/10611860600874538.
One-third of drugs in development are water insoluble and one-half fail in trials because of poor pharmacokinetics. Block copolymer micelles are nanosized particles that can solubilize hydrophobic drugs and alter their kinetics in vitro and in vivo. However, block copolymer micelles are not solely passive drug containers that simply solubilize hydrophobic drugs; cells internalize micelles. To facilitate the development of advanced, controlled, micellar drug delivery vehicles, we have to understand the fate of micelles and micelle-incorporated drugs in cells and in vivo. With micelle-based drug formulations recently reaching clinical trials, the impetus for answers is ever so strong and detailed studies of interactions of micelles and cells are starting to emerge. Most notably, the question arises: Is the internalization of block copolymer micelles carrying small molecular weight drugs an undesired side effect or a useful means of improving the effectiveness of the incorporated drugs?
处于研发阶段的药物中有三分之一是水不溶性的，并且有一半在试验中因药代动力学不佳而失败。嵌段共聚物胶束是纳米级颗粒，能够增溶疏水性药物并在体外和体内改变其动力学。然而，嵌段共聚物胶束并非仅仅是简单增溶疏水性药物的被动药物载体；细胞会摄取胶束。为了促进先进的、可控的胶束药物递送载体的研发，我们必须了解胶束以及载药胶束在细胞和体内的命运。随着基于胶束的药物制剂最近进入临床试验阶段，寻求答案的动力变得愈发强烈，并且关于胶束与细胞相互作用的详细研究也开始出现。最值得注意的是，问题出现了：携带小分子药物的嵌段共聚物胶束的内化是一种不良副作用还是提高所载药物有效性的有用手段？
