Block copolymer micelles formation factors

By covalent linkage of different types of molecules it is possible to obtain materials with novel properties that are different from those of the parent compounds. Examples of such materials are block-copolymers, soaps, or lipids which can self-assemble into periodic geometries with long-range order. Due to their amphiphilic character, these molecules tend to micellize and to phase-separate on the nanometer scale. By this self-assembly process the fabrication of new na-noscopic devices is possible, such as the micellization of diblock-co-polymers for the organization of nanometer-sized particles of metals or semiconductors [72 - 74]. The micelle formation is a dynamic process, which depends on a number of factors like solvent, temperature, and concentration. Synthesis of micelles which are independent of all of these factors via appropriately functionalized dendrimers which form unimolecular micelles is a straightforward strategy. In... 

The efficiency of a block copolymer is fimited by the formation of micelles in bulk phases and by the kinetic factors. Consequently, the block copolymer used as a compatibilizer should be designed by taking thermodynamic and kinetic parameters into account to achieve the desired effects. Thus the stmcture and transitions in copolymers and homopolymer/copolymer systems is of great interest. 

The ability of amphiphilic block copolymers to modulate multi drag resistance related processes has been demonstrated the first time more than 10 years ago. Nowadays, the efflux pump inhibitory activity of amphiphilic block copolymers is used in two main areas. First, to improve the transport of efflux pump substrates across the blood brain barrier (BBB) and second, in cancer therapy. It has been shown that in the presence of amphiphilic block copolymers higher concentrations of certain anhcancer drugs, which are known as efflux pump substrates, can be found in the brain. Within the current chapter, recent developments in the field of amphiphilic block copolymer mediated efflux pump inhibition are discussed. Besides presenting data from in vitro and vivo studies, also the mechanisms involved in efflux pump inhibition are addressed. In addition, the influence of hydrophilicity/lipophilicity of various amphiphilic block copolymers as well as factors such as micelle formation on the efflux pump inhibitory activity are explained. 

Another important factor which is not directly related to the hydrophilicity/lipophilicity ratio of various pluronics but which strongly influences the efflux pump inhibitoiy activity of pluronics is micelle formation. Above a certain concentration, the so called critical micelle concentration (CMC), amphiphilic block copolymers self assemble into micelles. It has been demonstrated, that the efflux pump inhibitory activity of pluronics increases with increasing pluronie concentrations, but only until the CMC is reached. Above the CMC, substrate accumulation in cancer cells could not be further increased or was found to even decrease [37]. Therefore, the occurrence of pluronie unimers can be regarded as the crucial prerequisite for the efflux pump inhibitory activity of pluronics [37]. As one mechanism for efflux pump inhibition has been identified to be ATP depletion, it seems necessary that the pluronie unimers are transported into the cells in order to exert this action. 

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