Drug-Dependent Modulation of Micelle Morphology and Encapsulation in Triton X-100 Systems

Abstract

Micelle-based drug delivery systems offer promising strategies for enhancing the solubility and bioavailability of poorly water-soluble drugs. In this study, we employed all-atom molecular dynamics simulations to investigate the structural and dynamic interactions between Triton X-100 micelles and three small-molecule therapeutics (aspirin, atenolol, and felodipine) selected for their diverse physicochemical properties. We found that the drug-micelle interactions are predominantly governed by the hydrophilic head groups of Triton X-100, with limited penetration into the hydrophobic core. Atenolol exhibited the highest encapsulation within the micelle core, while felodipine showed the greatest overall encapsulation, consistent with their respective hydrophobicities (log P values). Drug loading induced distinct alterations in micelle shape and volume, with atenolol-loaded micelles showing the most pronounced deviation from sphericity. We show that aromatic and polar functional groups drive both drug-drug and drug-surfactant interactions. These insights enhance our molecular-level understanding of nonionic surfactant micelles as drug carriers and provide a comparative framework for the rational design of tailored drug delivery systems.