Structure and design of polymeric surfactant-based drug delivery systems

The review concentrates on the use of polymeric micelles as pharmaceutical carriers. Micellization of biologically active substances is a general phen omenon that increases the bioavailability of lipophilic drugs and nutrients . Currently used low-molecular-weight pharmaceutical surfactants have low t oxicity and high solubilization power towards poorly soluble pharmaceutical s. 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 th e other hand, amphiphilic block co-polymers are also known to form spherica l micelles in solution. These micelles have very high solubilization capaci ty and rather low CMC value that makes them very stable in vivo. Amphiphili c block co-polymers suitable for micelle preparation are described and vari ous types of polymeric micelles are considered as well as mechanisms of the ir 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 a nd steric protection in vivo are considered with a special emphasis on long circulating drug delivery systems. Advantages and disadvantages of micelle s when compared with other drug delivery systems are considered. New polyme r-lipid amphiphilic compounds such as diacyillipid-polyethylene glycol. are described and discussed. These compounds are very attractive from a practi cal point of view, since they easily micellize yielding extremely stable mi celles with very high loading capacity. Micelle passive accumulation in the areas with leaky vasculature (tumors, infarct zones) is discussed as an im portant physiology-based mechanism of drug delivery into certain target zon es. Targeted polymeric micelles prepared by using thermo- or pH-sensitive c omponents or by attaching specific targeted moieties (such as antibodies) t o their outer surface are described as well as their preparation and some i n vivo properties. The fast growing field of diagnostic micelles is analyze d. 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 experim ents are presented. (C) 2001 Elsevier Science B.V All rights reserved.