Polymer micelles drug solubilization

Solubilization oftropicamide, a poorly water-soluble mydriatic/cycloplegicdrug, by poloxamers or Pluronics was studied (Saettone et al., 1988). The polymers evaluated as solubilizers for the drug included L-64, P-65, F-68, P-75, F-77, P-84, P-85, F-87, F-88, and F-127. The authors measured a range of physicochemical properties, such as solubility oftropicamide in polymer solutions, partition coefLcient of the drug between isopropyl myristate and copolymer solutions, critical micelle concentration of the copolymers, and viscosity of the copolymeric solutions containing tropicamide. 

Several methods for effective solubilization of drugs into polymer micelles have been developed (Fig. 2). The dialysis method (Fig. 2A) is most widely used for many polymeric micelle systems. The first step involves the dissolution of both polymer and drug in a water-miscible organic solvent such as acetonitrile, acetone, dimethylformamide, or ethanol. Then, the polymer-drug solution is dialyzed against water. As the organic... 

Recently, novel micellar systems based on block copolymers have been developed for drug solubilization and delivery (Houlton, 2003). One example of such a system is poly-ethylene glycol-poly-aspartic acid block copolymer, which spontaneously forms into colloidal particles (micelles) in aqueous solution. In this type of micelle, the drug molecule will experience an environment characterized by the physicochemical properties of the polymer (see Section 16.2.2.3). 

Solubilization of vinylpyrrolidone, acrylic acid, and A,A -methylene-bis-acrylamide in AOT-reversed micelles allowed the synthesis in situ of a cross-linked polymer with narrow size distribution confined in the micellar domain. These particles displayed high entrapment efficiency of small hydrophilic drugs and have been considered interesting drug delivery systems [239],... 

Polymeric micelles Micelles consisting of amphiphilic polymers Loading hydrophobic drugs in the core for solubilization, targeted delivery, and controlled release 35,36... 

The solid dispersion method (Fig. 2B) was used for solubilization of paclitaxel into PEG-poly(D,L-lactide) diblock copolymer micelles. Paclitaxel and the polymer were dissolved in acetonitrile followed by evaporation of the solvent under a stream of nitrogen at 60°C to obtain a gel-like polymer-drug matrix. Dissolution of the solid matrix in water at about 60° C with stirring led to formation of drug-loaded micelles. Because a heating is needed to completely dissolve the polymer-drug matrix, this method may not be not desirable for thermally unstable drugs. 

Water-soluble polymers conjugated with lipids can form micelles in aqueous media, and they can be used for the solubilization and enhanced delivery of a variety of sparingly soluble drugs. The basic structures of these polymer-lipid conjugates are similar to amphiphilic block copolymers except for the fact that hydrophobic parts are composed of lipids instead of hydro-phobic polymers. For example, a hydrophilic PEG block is conjugated with phosphatidylethanolamine. ... 

These are stable micelles that are formed with polymeric surfactants. Amphiphilic block copolymers such as the pluronics (polyoxyethylene-polyoxypropylene block copolymers) are able to self-assemble into polymeric micelles and hydrophobic drugs may be solubilized within the core of the micelle or, alternatively, conjugated to the micelle-forming polymer. Although micelles are rather dynamic systems that continuously exchange units between the micelle structure and the free units in solution, those composed of polyoxyethylene - poly(aspartic acid) have been found sufficiently... 

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