Torchilin V P
Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Mugar Building, Room 312, 360 Huntington Avenue, Boston, Massachusetts 02115, USA.
Pharm Res. 2007 Jan;24(1):1-16. doi: 10.1007/s11095-006-9132-0. Epub 2006 Nov 16.
Micelles, self-assembling nanosized colloidal particles with a hydrophobic core and hydrophilic shell are currently successfully used as pharmaceutical carriers for water-insoluble drugs and demonstrate a series of attractive properties as drug carriers. Among the micelle-forming compounds, amphiphilic copolymers, i.e., polymers consisting of hydrophobic block and hydrophilic block, are gaining an increasing attention. Polymeric micelles possess high stability both in vitro and in vivo and good biocompatibility, and can solubilize a broad variety of poorly soluble pharmaceuticals many of these drug-loaded micelles are currently at different stages of preclinical and clinical trials. Among polymeric micelles, a special group is formed by lipid-core micelles, i.e., micelles formed by conjugates of soluble copolymers with lipids (such as polyethylene glycol-phosphatidyl ethanolamine conjugate, PEG-PE). Polymeric micelles, including lipid-core micelles, carrying various reporter (contrast) groups may become the imaging agents of choice in different imaging modalities. All these micelles can also be used as targeted drug delivery systems. The targeting can be achieved via the enhanced permeability and retention (EPR) effect (into the areas with the compromised vasculature), by making micelles of stimuli-responsive amphiphilic block-copolymers, or by attaching specific targeting ligand molecules to the micelle surface. Immunomicelles prepared by coupling monoclonal antibody molecules to p-nitrophenylcarbonyl groups on the water-exposed termini of the micelle corona-forming blocks demonstrate high binding specificity and targetability. This review will discuss some recent trends in using micelles as pharmaceutical carriers.
胶束是具有疏水核心和亲水外壳的自组装纳米级胶体颗粒,目前已成功用作水不溶性药物的药物载体,并展现出一系列作为药物载体的诱人特性。在形成胶束的化合物中,两亲性共聚物,即由疏水嵌段和亲水嵌段组成的聚合物,正受到越来越多的关注。聚合物胶束在体外和体内均具有高稳定性和良好的生物相容性,并且能够增溶多种难溶性药物,许多载药胶束目前正处于临床前和临床试验的不同阶段。在聚合物胶束中,脂质核心胶束形成了一个特殊的类别,即由可溶性共聚物与脂质的缀合物(如聚乙二醇 - 磷脂酰乙醇胺缀合物,PEG - PE)形成的胶束。包含脂质核心胶束在内的聚合物胶束,携带各种报告(造影)基团,可能成为不同成像模式下的首选成像剂。所有这些胶束也可用作靶向给药系统。靶向可以通过增强渗透和滞留(EPR)效应(进入血管系统受损的区域)、制备刺激响应性两亲性嵌段共聚物的胶束或通过将特定的靶向配体分子连接到胶束表面来实现。通过将单克隆抗体分子偶联到胶束冠层形成嵌段的水暴露末端上的对硝基苯基羰基基团制备的免疫胶束表现出高结合特异性和靶向性。本综述将讨论使用胶束作为药物载体的一些最新趋势。