Interaction of Chlorpromazine with Phospholipid Membranes:  A Monolayer and a Microelectrophoresis Approach

Abstract

Chlorpromazine penetration into the lipid core of the membrane was demonstrated through measurements on lipid monolayers (surface pressure and surface potential). The surface pressure measurements allow us to calculate the intrinsic binding constant (partition coefficient) for the lipid-Chlorpromazine interaction. This latter value is in correct agreement with the obtained results by electrophoretic mobilities measurements on liposomes.

Lipid–Drug Interaction and Colligative Properties in Phospholipid Vesicles

“…The drug penetration into the lipid layer was confirmed by surface potential measurements on monolayers (14).…”

“…All the measurements were carried out in the stationary level (13,14) of the cylindrical capillary cell (length 8 cm) with an applied voltage of approximately 40 V (DC) at 25°C. The migration rate of the particles was determined at least 10 times in each direction.…”

“…In that case, the lipidic membrane will be considered as a separate phase, the "hydrophobic phase," and a partition coefficient can be determined to characterize the passage of the drug from the aqueous phase to the lipidic phase. It was suggested that Chlorpromazine (a tricyclic molecule having a neuroleptic activity) and several local anaesthetics are examples of that class of drugs (13,14).…”

“…For this last molecule, the partition coefficient was calculated through electrophoretic mobility measurements on liposomes and surface pressure measurements on monolayers (14), using different lipids (anionic and neutral, having different fluidities) both at "acidic" and at "basic" pH (the pK a of the drug's amino group is near 8.6 (9)). The drug penetration into the lipid layer was confirmed by surface potential measurements on monolayers (14).…”

Association of Blood Clotting Factors I and VII with Phospholipid Monolayers at the Air–Water Interface

“…Such lipid membranes are suitable model membranes for probing specific lipid-protein interactions, and other researchers have reported the use of similar methods for studying lipid interactions with drugs and viral agents (6,7). A protein solution is injected into the subphase beneath the lipid monolayer and then given time to interact with the lipid.…”