The composition-dependent presence of free (micellar) alkylphospholipid in liposomal formulations of octadecyl-1,1-dimethyl-piperidino-4-yl-phosphate affects its cytotoxic activity in vitro

Item Type:	Article
Title:	The composition-dependent presence of free (micellar) alkylphospholipid in liposomal formulations of octadecyl-1,1-dimethyl-piperidino-4-yl-phosphate affects its cytotoxic activity in vitro
Creators Name:	Zeisig, R. and Mueller, K. and Maurer, N. and Arndt, D. and Fahr, A.
Abstract:	This study was performed to investigate the effect of cholesterol content, surface charge and sterical stabilization on the physico-chemical properties of liposomes prepared from the cancerostatic alkylphospholipid, octadecyl-1,1-dimethyl-piperidino-4-yl-phosphate (D21266), and their relationship to in vitro cytotoxicity. Stable incorporation of OPP into liposomes was found to be highly dependent on the cholesterol content. 31P-NMR spectroscopy as well as analysis of the lipid composition of OPP-containing liposome formulations revealed an increase in the amount of non-liposome-associated, micellar OPP as the cholesterol content decreased. The fraction of non-liposome-associated OPP constituted about 10% of total OPP when cholesterol was present in equimolar amounts (45.5/45.5 mol %) and increased to approximately 30% at a twofold excess of OPP over cholesterol (58.8/29.4 mol %). In monolayer incorporation studies it was shown that the existence of an increasing micellar pool of lipids leads to increased lipid transfer into the target monolayer. Liposome formulations containing more OPP than cholesterol were also found to display greater cytotoxicity. However, all liposome formulations were less cytotoxic than pure (micellar) OPP. Cytotoxicity was not affected by the incorporation of N-methoxy-polyethyleneglycol 2000-phosphoethanolamine, a lipid that is known to reduce liposome uptake into phagocytic cells. The results demonstrate that the increase in cell toxicity correlates with the increase in non-liposome-associated, micellar OPP, which can readily exchange into cellular membranes.
Keywords:	Alkylphospholipid, Breast Cancer, Cytotoxicity, Liposomes, Micelles, Monolayer
Source:	Journal of Membrane Biology
ISSN:	0022-2631
Publisher:	Springer
Volume:	182
Number:	1
Page Range:	61-69
Date:	1 January 2001
Official Publication:	https://doi.org/10.1007/s00232-001-0027-z
PubMed:	View item in PubMed

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