Thermodynamics of partitioning of the antimalarial drug mefloquine in phospholipid bilayers and bulk solvents.
The antimalarial drug mefloquine binds avidly to phospholipids in biomembranes. The thermodynamics of the partitioning process in dimyristoylphosphatidylcholine (DMPC) bilayers was investigated to give some insight into the drug-phospholipid interaction. Thermodynamic parameters for the partition equilibria were evaluated from the equilibrium partition coefficients measured as a function of temperature. Negative values of delta H and delta S were obtained for the transfer of mefloquine from the aqueous to the gel phase of the phospholipid. The partitioning is enthalpy controlled which suggests that mefloquine interacts strongly with the phospholipid phase. In contrast, the partitioning of mefloquine into the liquid crystalline phase of DMPC is entropy controlled which is typical of a hydrophobic interaction between mefloquine and the aqueous phase. The partitioning of mefloquine into the bulk solvents octanol and hexane were found to be enthalpy and entropy controlled, respectively. The enthalpy dominated partitioning of mefloquine into gel phase DMPC and octanol is attributed to the occurrence of hydrogen bonding and van der Waals interactions between solute and solvent. The flat shape of mefloquine may further aid its interaction with the orderly domains of the lipidic/organic phase. This is apparent from a comparison of the partitioning characteristics of another structurally related but conformationally different molecule, quinine into DMPC and octanol.
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Department of Pharmacy, National University of Singapore, Kent Ridge Crescent, Singapore.
Ngiam
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D020003:1-Octanol / Q000737:chemistry; D000962:Antimalarials / Q000737:chemistry*; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D005782:Gels; D006586:Hexanes / Q000737:chemistry; D006860:Hydrogen Bonding; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D015767:Mefloquine / Q000737:chemistry*; D011803:Quinine / Q000737:chemistry; D012997:Solvents / Q000737:chemistry*; D013696:Temperature; D013816:Thermodynamics
D000962:Antimalarials; D005782:Gels; D006586:Hexanes; D008051:Lipid Bilayers; D008081:Liposomes; D012997:Solvents; C026385:n-hexane; D011803:Quinine; D020003:1-Octanol; D015767:Mefloquine; D004134:Dimyristoylphosphatidylcholine