alexa Structure and design of polymeric surfactant-based drug delivery systems.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Molecular and Genetic Medicine

Author(s): Torchilin VP

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Abstract 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.
This article was published in J Control Release and referenced in Journal of Molecular and Genetic Medicine

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