pH-dependent association of SN-38 with lipid bilayers of a novel liposomal formulation

pH-dependent association of SN-38 with lipid bilayers of a novel liposomal formulation
August 2005
Viktor Peikov, Sydney Ugwu, Manjeet Parmar, Allen Zhang and Imran Ahmad, Research & Development, NeoPharm Inc., Waukegan, IL 60085, USA
International Journal of Pharmaceutics Volume 299, Issues 1-2 , 11 August 2005, Pages 92-99
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Abstract
The aim of this study was to determine the location of SN-38 molecules in a liposomal formulation as a function of pH. Steady-state fluorescence polarization anisotropy and gel filtration studies of blank (placebo) liposomes, liposomes containing SN-38 and SN-38 solutions (in some cases suspensions) were conducted before lyophilization and after re-hydration at different pH conditions. SN-38, l-(4-trimethylammoniumphenyl)-6-phenyl-l,3,5-hexatriene p-toluenesulfonate (TMA?DPH), N-((4-(6-phenyl-l,3,5-hexatrienyl)phenyl)propyl)trimethylammonium p-toluenesulfonate (TMAP?DPH) and l,6-diphenyl-l,3,5-hexatriene (DPH) were used as fluoroprobes in the polarization anisotropy measurements. The localization of SN-38 was governed by the degree of hydrophobicity of the drug molecules. At high pH, SN-38 is in its inactive, hydrophilic form and partitioned into the water phase of the liposome suspensions. In lyophilized LE-SN38 liposomes re-hydrated with low pH buffer, SN-38 was found at the water?lipid interface of the bilayer.