Influence of cholesterol analogues on transmembrane ph gradients in trapping of amine drug in liposome

Abstract

Transmembrane movement of amine drugs (such as propranolol) in response to pH gradients had been investigated. It was shown that propranolol could accumulated rapidly into REVs composed of EPC exhibiting pH gradient (inside acidic). The transmembrane propranolol gradients formed in REVs systems exhibiting ∆pH (inside acidic) indicated that the transport process could be dictated by movement of the neutral form of propranolol which redistributed according to a simple Henderson-Hasselbach equilibrium. This active loading gave rise to trapping efficiencies as high as 98%. The influence of internal and external pH, interior buffering capacity, drug-to-lipid ratio and lipid composition on propranolol uptake into REVs systems in response to transmembrane pH gradients had been estimated. It was shown that decreasing the interior pH, increasing the interior buffering capacity and increasing the (saturated) acyl chain length of PC molecules all resulted in increased drug uptake. A study of influence of the cholesterol and cholesterol analogues on drug uptake revealed that cholesterol and hydroxyl cholesterol analogues (EPC:chol or analogue 2:1, by mol) decreased entrapped drug /lipid ratio, but prolonged its retention.