Partitioning of anticancer drug 5-fluorouracil in micellar media explored by physicochemical properties and energetics of interactions: Quantitative insights for implications in drug delivery

Abstract

Drug delivery vehicles such as micelles, vesicles and other nanoemulsions are necessary for enhanced bioavailability of drugs in the body. We have measured and correlated physicochemical properties of an anticancer drug 5-fluorouracil in the micelles of anionic surfactant sodium dodecyl sulfate. cationic surfactant hexadecyltrimethylammonium bromide, and non-ionic surfactant triton X-100 with the energetics of interactions. Thermodynamic signatures accompanying the partitioning of drug into surfactant micelles along with standard partial molar volume and standard partial molar compressibilities of transfer from water to the micelles have been interpreted in terms of strength, nature and extent of partitioning. Functional groups on the drug responsible for interaction/partitioning in micelles have been identified. Interaction of 5-fluorouracil in two or three sequential partitioning behavior depending on the nature of the surfactant micelles has enabled detailed mechanistic analysis of the partitioning process. Structure-property-energetics relationship to obtain deeper insights into the nature of interaction between the drug and micelles has been addressed. Such studies provide information on the significance of functional groups on the drug molecule which can be modified for optimum partitioning in drug delivery vehicles to account for effective target oriented release.