Partitioning and Localization of Spin-Labeled Amantadine in Lipid Bilayers: An Epr Study

• Published in: Journal of pharmaceutical sciences Vol. 87; no. 10; pp. 1249 - 1254
• Main Authors: Subczynski, Witold K., Wojas, Jerzy, Pezeshk, Vida, Pezeshk, Abbas
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.10.1998; John Wiley & Sons, Inc; Wiley; American Pharmaceutical Association
• Subjects: Amantadine - analysis; Antiviral Agents - analysis; Biological and medical sciences; Electron Spin Resonance Spectroscopy; General pharmacology; Lipid Bilayers - chemistry; Liposomes; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Spin Labels; Water; Amantadine; Solubility; EPR spectrometry; Partition coefficient; Artificial membrane; Antiparkinson agent; In vitro; Physical properties; Spin labelling; Biphasic system; Antiviral; Property structure relationship; Physicochemical properties
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1021/js970381n

EPR was used to study the distribution of the spin-labeled amantadine (AA-SL) between the bulk hydrophobic-hydrocarbon solvent, light paraffin oil, and water and between hydrophobic-hydrocarbon chain region of lipid membranes and water. The AA-SL molecules were soluble in both hydrophobic and polar regions of investigated systems. It was shown that the partition coefficient of AA-SL between the hydrocarbon region of the L-α-dimyristoylphos-phatidylcholine fluid-phase membrane and water is much higher than between bulk hydrocarbon solvent and water. Furthermore, the partitioning of AA-SL into membranes of multilamellar liposomes made of L-α-dimyristoylphosphatidylcholine, L-α-dipalmitoylphosphatidyl-choline, and L-α-distearoylphosphatidylcholine was studied as a function of temperature, indicating no abrupt change at the main phase transition of these membranes. It is also clear from our data that AA-SL can penetrate into the gel-phase membrane practically with the same partitioning as into the fluid-phase membrane. Furthermore, it was shown that at least part of the AA-SL molecule is deeply buried in the hydrocarbon chain region of the membrane.