pH-dependent association of SN-38 with lipid bilayers of a novel liposomal formulation.
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.
Research & Development, NeoPharm Inc., Waukegan, IL 60085, USA.
Viktor
V
Peikov
Sydney
S
Ugwu
Manjeet
M
Parmar
Allen
A
Zhang
Imran
I
Ahmad
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry; D002308:Cardiolipins / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D002850:Chromatography, Gel; D004161:Diphenylhexatriene / Q000031:analogs & derivatives; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D000077146:Irinotecan; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D013696:Temperature; D059004:Topoisomerase I Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D002308:Cardiolipins; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D059004:Topoisomerase I Inhibitors; D004161:Diphenylhexatriene; C033628:1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene; D000077146:Irinotecan; D002784:Cholesterol; C017251:1,2-oleoylphosphatidylcholine; D002166:Camptothecin