Spin label partitioning in lipid vesicles. A model study for drug encapsulation.
In this paper we attempt to outline some features which determine the encapsulation of small molecules into lipid vesicles. Spin labels derived from five carboxylic acids of different lengths were synthesized and incorporated in varying amounts into multilamellar and unilamellar vesicles made up of four different phosphatidylcholines. The influence on the release process of the bilayer rigidity and of the hydrophobicity of the entrapped molecule was systematically studied. The hydrophobicity is of critical importance and was estimated by measuring the partition coefficient (P) between octanol and buffer. In multilamellar vesicles, molecules characterized by extreme P values (log P less than -0.3 and log P greater than 5) can be efficiently entrapped. The rate of leakage is related to the P value according to a bell-shaped curve. Moreover, gel state of the bilayer and long acyl chains of the lipids are properties which favor a good entrapment. Small unilamellar vesicles may be formed in the presence of high concentrations of hydrophilic and lipophilic spin labels. However, the formation of unilamellar vesicles produces a significant reduction of the internal volume and of the entrapped water-soluble spin lables. High fractions of lipid-soluble spin labels can be incorporated in unilamellar vesicles but the vesicle stability is diminished.
D002264:Carboxylic Acids; D004578:Electron Spin Resonance Spectroscopy; D005227:Fatty Acids; D008081:Liposomes; D004364:Pharmaceutical Preparations; D010713:Phosphatidylcholines; D013113:Spin Labels; D013329:Structure-Activity Relationship
D002264:Carboxylic Acids; D005227:Fatty Acids; D008081:Liposomes; D004364:Pharmaceutical Preparations; D010713:Phosphatidylcholines; D013113:Spin Labels