Premium
Role of bis(monoacylglycero)phosphate in propranolol binding to phospholipid membranes under acidic conditions as measured by high‐performance frontal analysis/capillary electrophoresis
Author(s) -
Hamaguchi Ryohei,
Kuroda Yukihiro,
Tanimoto Toshiko,
Haginaka Jun
Publication year - 2012
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.201200324
Subject(s) - phospholipidosis , chemistry , liposome , phospholipid , phosphatidylcholine , phosphatidylglycerol , membrane , endosome , biophysics , chromatography , amphiphile , phosphorylcholine , phosphatidylserine , biochemistry , organic chemistry , biology , receptor , copolymer , polymer
Bis(monoacylglycero)phosphate (BMP) is localized in acidic organelles such as late endosomes or lysosomes. It has been reported that BMP levels increase under phospholipidosis induced by cationic amphiphilic drugs. In the present study, the effect of BMP on the binding of propranolol (PRO) to phospholipid liposomes under acidic conditions was investigated. Binding experiments were conducted by high‐performance frontal analysis/capillary electrophoresis. PRO showed nonspecific binding to BMP‐containing liposomes (BMP:phosphatidylcholine = 1:4), when numbers of bound drug molecules per lipid molecule ( r ) ranged 0.01–0.06. Total binding affinity increased depending on the BMP content. Binding affinity was decreased by low ionic strength, or by substitution of BMP with diacylglycerol, suggesting that electrostatic interactions were involved. The binding‐enhancement effect of BMP was almost equivalent to that of phosphatidylglycerol, and slightly larger than that of phosphatidylserine. An acidic environment (pH 5.0) decreased total binding affinity to BMP‐containing liposomes. This could be explained by the pH‐partition theory (i.e., the loss in affinity was caused by a decrease in the neutral form of the drug accessible to the membrane core). These results suggest that PRO binding is enhanced by BMP in late endosomes or lysosomes, whereas an acidic environment weakens such binding.