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Pharm Res. 1998 May;15(5):739-44.

Towards the predictability of drug-lipid membrane interactions: the pH-dependent affinity of propanolol to phosphatidylinositol containing liposomes.

Author information

1
Biopharmacy, Department of Pharmacy, ETH Zürich, Switzerland.

Abstract

PURPOSE:

Prediction of the pH-dependent affinity of (RS)-[3H]propranolol to mixed phosphatidylcholine (PhC)/phosphatidylinositol(Phl) membranes from the partitioning in the single lipid liposome/buffer systems.

METHODS:

Partition studies in liposome/buffer systems were performed by means of equilibrium dialysis at 37 degrees C between pH 2 and 11 at a molar propranolol to lipid ratio of 10(-6) to 10(-5) in the membrane. Results. The Phl membrane more strongly attracts the protonated (RS)-[3H]propranolol than the neutral solute, i.e. the partition coefficient of the protonated base (Pi) is 17'430+/-1320, P of the neutral compound (Pn) is 3110+/-1650. In the PhC-liposome system Pi is 580+/-17, Pn 1860+/-20. The partition coefficients show an exponential dependence on the molar Phl fraction in mixed liposomes. The partitioning in mixed PhC/Phl membranes is predictable from Pn and Pi in the single lipid liposome systems.

CONCLUSIONS:

The negative charge of biological lipid membranes causes strong electrostatic interactions with positively charged solutes. This strong attraction is not predictable from the octanol/buffer partition system, but it is important regarding drug accumulation in the tissue and drug attraction by certain lipids in the vicinity of membrane proteins.

PMID:
9619783
DOI:
10.1023/a:1011923103938
[Indexed for MEDLINE]

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