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Halofantrine-phospholipid interactions: monolayer studies
1Department of Pharmacy, National University of Singapore, Singapore. phagoml@nus.edu.sg
Abstract:
The antimalarial agent halofantrine penetrates dipalmitolylphosphatidylcholine (DPPC) monolayers resulting in an increase in surface pressure and an expansion in area occupied by the lipid components of the monolayer. This phenomenon is observed at concentrations (0.05-0.2 microm) of halofantrine that have no surface activity. Penetration increases with drug concentration and is greatest at low initial surface pressures of the monolayer. A critical surface pressure of the DPPC monolayer has been determined from constant area and constant pressure conditions. The magnitude of these values support the hypothesis that halofantrine readily penetrates the DPPC monolayers. The presence of cholesterol in the DPPC monolayer hampers penetration and a lower critical surface pressure is obtained under such conditions. Even then, a slower rate of penetration is observed only in monolayers maintained at high initial surface pressures (10, 15 mN/m), corresponding to the liquid condensed phase of the monolayer, and not at low surface pressures (2.5, 5.0 mN/m). These results help to give a better understanding of the dynamics of the halofantrine-phospholipid interaction as well as the pharmacodynamic character of the drug.
Insights
The antimalarial drug halofantrine readily penetrates dipalmitolylphosphatidylcholine (DPPC) lipid monolayers, affecting their surface properties. Cholesterol hinders this penetration, particularly in certain lipid phases.
Area of Science:
- Biophysics
- Pharmacology
- Materials Science
Background:
- Halofantrine is an antimalarial drug.
- Dipalmitolylphosphatidylcholine (DPPC) is a common phospholipid.
- Understanding drug-lipid interactions is crucial for pharmacodynamics.
Purpose of the Study:
- To investigate the interaction between halofantrine and DPPC monolayers.
- To determine the effect of halofantrine concentration and surface pressure on DPPC monolayer penetration.
- To assess the influence of cholesterol on halofantrine-DPPC interactions.
Main Methods:
- Studied halofantrine penetration into DPPC monolayers using surface pressure measurements.
- Varied halofantrine concentrations (0.05-0.2 microm) and initial surface pressures.
- Investigated the effect of cholesterol incorporation into DPPC monolayers.
Main Results:
- Halofantrine penetrates DPPC monolayers, increasing surface pressure and area.
- Penetration is concentration-dependent and more pronounced at low initial surface pressures.
- Cholesterol significantly reduces halofantrine penetration, especially at high surface pressures (liquid condensed phase).
Conclusions:
- Halofantrine readily penetrates DPPC monolayers, supporting its pharmacodynamic profile.
- Cholesterol acts as a barrier to halofantrine penetration in DPPC monolayers.
- These findings elucidate halofantrine-phospholipid dynamics and drug behavior.