ABSTRACT
According to early experiments with natural extracts, phosphatidylcholines (PCs) are widely considered essentially non-toxic. In addition to these physiological mixed-chain PCs, many different synthetic diacyl-PCs are currently available, but they have never been systematically evaluated for any interference with cell proliferation. We thus investigated the cell proliferation of several cell lines in the presence of various liposomes consisting of a single PC component and cholesterol. Most of the PCs investigated did not interfere with cell proliferation, supporting the notion that most PCs are safe excipients. Significant IC50 values below 0.5mM were detected for PC(12:0/12:0), PC(14:1/14:1)trans and all diacyl-PCs containing two polyunsaturated fatty acids (PUFAs). The ω-3 PC(22:6/22:6) was the most toxic PC assessed, revealing IC50 values below 100 µM, but no rule concerning ω-3/6 configuration or acyl chain length could be observed. Physiological mixed-chain PCs containing PUFAs were much less toxic than respective non-physiological diacyl-PCs. All trans fatty acids in diacyl-PCs interfered more with proliferation than their respective cis-configured counterparts. Depending on the concentration, those diacyl-PCs not only inhibited proliferation but also induced cell death. Unlike the non-toxic PCs usually used for liposomal drug delivery, the elucidated diacyl-PCs may be worthy of further examination to eventually construct a toxic shell for toxic drugs, thereby enhancing anticancer drug delivery via lipid particles.
