Torchilin V P
Department of Pharmaceutical Sciences, Bouve College of Health Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02129, USA.
J Control Release. 2001 Jun 15;73(2-3):137-72. doi: 10.1016/s0168-3659(01)00299-1.
The review concentrates on the use of polymeric micelles as pharmaceutical carriers. Micellization of biologically active substances is a general phenomenon that increases the bioavailability of lipophilic drugs and nutrients. Currently used low-molecular-weight pharmaceutical surfactants have low toxicity and high solubilization power towards poorly soluble pharmaceuticals. However, micelles made of such surfactants usually have relatively high critical micelle concentration (CMC) and are unstable upon strong dilution (for example, with the blood volume upon intravenous administration). On the other hand, amphiphilic block co-polymers are also known to form spherical micelles in solution. These micelles have very high solubilization capacity and rather low CMC value that makes them very stable in vivo. Amphiphilic block co-polymers suitable for micelle preparation are described and various types of polymeric micelles are considered as well as mechanisms of their formation, factors influencing their stability and disintegration, their loading capacity towards various poorly soluble pharmaceuticals, and their therapeutic potential. The basic mechanisms underlying micelle longevity and steric protection in vivo are considered with a special emphasis on long circulating drug delivery systems. Advantages and disadvantages of micelles when compared with other drug delivery systems are considered. New polymer-lipid amphiphilic compounds such as diacyillipid-polyethylene glycol, are described and discussed. These compounds are very attractive from a practical point of view, since they easily micellize yielding extremely stable micelles with very high loading capacity. Micelle passive accumulation in the areas with leaky vasculature (tumors, infarct zones) is discussed as an important physiology-based mechanism of drug delivery into certain target zones. Targeted polymeric micelles prepared by using thermo- or pH-sensitive components or by attaching specific targeted moieties (such as antibodies) to their outer surface are described as well as their preparation and some in vivo properties. The fast growing field of diagnostic micelles is analyzed. Polymeric micelles are considered loaded with various agents for gamma, magnetic resonance, and computed tomography imaging. Their in vitro and in vivo properties are discussed and the results of the initial animal experiments are presented.
本综述着重于聚合物胶束作为药物载体的应用。生物活性物质的胶束化是一种普遍现象，它能提高亲脂性药物和营养物质的生物利用度。目前使用的低分子量药物表面活性剂毒性低，对难溶性药物具有高增溶能力。然而，由这类表面活性剂制成的胶束通常具有相对较高的临界胶束浓度（CMC），并且在强烈稀释时（例如静脉给药时与血容量混合）不稳定。另一方面，两亲性嵌段共聚物在溶液中也能形成球形胶束。这些胶束具有很高的增溶能力和相当低的CMC值，这使得它们在体内非常稳定。文中描述了适用于制备胶束的两亲性嵌段共聚物，探讨了各种类型的聚合物胶束及其形成机制、影响其稳定性和崩解的因素、它们对各种难溶性药物的负载能力以及治疗潜力。特别强调了长循环药物递送系统，探讨了胶束在体内的寿命和空间保护的基本机制。文中还讨论了胶束与其他药物递送系统相比的优缺点。介绍并讨论了新型聚合物 - 脂质两亲性化合物，如二酰基脂质 - 聚乙二醇。从实际应用角度来看，这些化合物极具吸引力，因为它们易于形成胶束，能产生具有极高负载能力的极其稳定的胶束。文中讨论了胶束在血管渗漏区域（肿瘤、梗死区域）的被动蓄积，这是一种基于生理学的重要药物递送机制，可将药物递送至特定靶区。文中描述了通过使用热敏或pH敏感成分或在其外表面连接特定靶向部分（如抗体）制备的靶向聚合物胶束及其制备方法和一些体内性质。分析了快速发展的诊断性胶束领域。聚合物胶束被认为可负载各种用于伽马、磁共振和计算机断层扫描成像的试剂。讨论了它们的体外和体内性质，并展示了初步动物实验的结果。
