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Research Article

Alkylphosphocholines and Alkylphosphocholine Liposomes

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Pages 91-98 | Published online: 28 Sep 2008
 

Abstract

Alkylphosphocholines (APC) are phosphocholine esters of aliphatic alcohols. They are compounds with a relatively simple chemical structure, but they inhibit cell proliferation by interacting with the plasma membrane. Though the structure of alkylphosphocholines is very similar to lysolecithins, liposome formation is possible under special conditions from these lipids. The direct cytotoxicity of APC liposomes against tumor and normal cells is generally reduced in comparison to the effects of micellar solutions of the APCs. The indirect, macrophage-mediated cytotoxicity is increased for the liposomal form. This is also observable for important steps of macrophage activation — release of nitric oxide radicals (NO) and tumor necrosis factor (TNF). On the other hand, avoiding of the mononuclear phagocyte system is possible for APC liposomes, which are sterically stabilized by incorporation of polyethylene glycol covalently linked to distearoylphos- phatidylethanolamine. Carbon clearance experiments demonstrate clearly a distinct reduced ingestion of sterically stabilized APC liposomes by the mononuclear phagocyte system. In one therapeutic application, distinct decrease in tumor burden could be demonstrated in nude mice bearing the breast carcinoma MaTu following treatment with sterically stabilized APC liposomes.

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