Department of Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, 15782-Santiago de Compostela, Spain.
Curr Drug Targets. 2011 Jul 1;12(8):1112-30. doi: 10.2174/138945011795906615.
Drug carriers tailored to fit the physicochemical properties of anticancer agents and the therapeutic peculiarities of tumor management are envisioned for improving the effectiveness/toxicity ratio of the current treatments. Polymeric micelles are attracting much attention owing to their unique beneficial features: i) core-shell structure capable to host hydrophobic drugs, raising the apparent solubility in aqueous medium; ii) size adequate for a preferential accumulation (passive targeting) within the tumor, exhibiting enhanced permeability and retention (EPR effect), and iii) unimers that modulate the activity of efflux pumps involved in multidrug resistance (MDR). This review focuses on amphiphilic poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) block copolymers, namely the linear poloxamers (Pluronic® or Lutrol®) and the X-shaped poloxamines (Tetronic®), as components of polymeric micelles able to play these three roles. Specific facets of poloxamers have been highlighted some years ago, but recently their wide range of possibilities is beginning to be fully elucidated and understood. Poloxamines are new excipients in the cancer arena and the comparison of their performance with that of poloxamers may enable to identify aspects of their architecture relevant for the optimization of micellar carriers. Clinical trials in progress indicate that drug-loaded polymeric micelles are beneficial regarding efficiency, safety, and compliance of the treatment and quality of life of the patients. The fact that some copolymers are already approved for internal use and several chemotherapy agents will be off patent soon may help to bring the clinical use of poloxamer- or poloxamine-based micelles into a reality in the coming years.
为了提高当前治疗方法的有效性/毒性比，人们设想了针对抗癌药物的物理化学性质和肿瘤治疗特点定制的药物载体。由于具有独特的有益特性，聚合物胶束引起了人们的极大关注：i）能够容纳疏水性药物的核壳结构，提高在水介质中的表观溶解度；ii）大小适合于在肿瘤内优先积累（被动靶向），表现出增强的渗透性和保留性（EPR 效应）；iii）单体调节多药耐药（MDR）相关外排泵的活性。本综述重点介绍两亲性聚（环氧乙烷）（PEO）和聚（环氧丙烷）（PPO）嵌段共聚物，即线性泊洛沙姆（Pluronic®或 Lutrol®）和 X 型泊洛沙胺（Tetronic®），作为能够发挥这三种作用的聚合物胶束的组成部分。几年前已经强调了泊洛沙姆的某些特定方面，但最近它们的广泛可能性开始得到充分阐明和理解。泊洛沙胺是癌症领域的新型赋形剂，比较它们的性能与泊洛沙姆的性能可以确定其结构的相关方面，这些方面对于优化胶束载体是重要的。正在进行的临床试验表明，载药聚合物胶束在治疗的效率、安全性、顺应性以及患者的生活质量方面是有益的。事实上，一些共聚物已经被批准用于内部使用，并且几种化疗药物将很快失去专利，这可能有助于在未来几年将基于泊洛沙姆或泊洛沙胺的胶束的临床应用变为现实。
