(377e) Molecular Thermodynamic Modelling of Micellar-Assisted Drug Delivery Systems
The key property of the molecular thermodynamic modeling approach for self-assembled systems is the free energy of micellization, which for mixed ionic surfactants in water consists of six contributions including: 1) the transfer of surfactant tails or drug molecule hydrophobic moieties from bulk water to the micellar core; 2) the creation of a micellar hydrocarbon core-water interface, which accounts for the molecular architecture of the drug molecule; 3) surfactant and drug tail chain packing within the micellar core (i.e., consideration that tails are constrained at the interface); 4) surfactant and drug molecule hydrophilic head group steric repulsions; 5) electrostatic effects between charged moieties and counterions; and 6) the entropic effect of mixing various species. The Gibbs free energy of micellization is minimized with respect to core minor radius for different shapes to determine the optimum shape, size and composition of micelle including degree of counterion binding. Key output from the model includes: 1) micellar composition as a function of bulk surfactant mole fraction; 2) drug solubility as a function of surfactant mole fraction; and 3) the molar solubilization capacity (drug solubility/surfactant concentration). These features and the optimum micelle size and shape are reported for each drug-surfactant system. Finally, CiEj surfactants are ranked according to their ability solubilize each model drug in the study.
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