Molecular dynamics simulation reveals the reliability of Brij-58 nanomicellar drug delivery systems for flurbiprofen

Abstract

• Brij-58/flurbiprofen drug delivery system is explored utilizing CGMD simulation. • Self-assembled formation of Brij-58 nanomicelle is deeply analyzed. • Spherical-to-cylindrical phase transition is observed in Brij-58 micelle. • The pharmacokinetics profile of flurbiprofen is examined via CGMD simulation. • Brij-58 disaggregates and solubilizes flurbiprofen at the core-corona interface. Incorporating drugs in the micellar assemblies of surfactants is a powerful way to enhance their solubility and therapeutic index. Although surfactant-based micelle formulations are studied experimentally, developing a reliable drug delivery system (DDS) can be costly, time-consuming, and risky. Herein, we apply a series of coarse-grained molecular dynamics (CGMD) simulations to polyoxyethylene-20-cetyl ether (Brij-58) micelle to demonstrate how it interacts with flurbiprofen in the aqueous solution. Targeting this purpose, one computational cell consisting of randomly distributed Brij-58 surfactants is examined to characterize the formed micelle during the self-assembly process. The obtained size of the aggregate is in good agreement with the experimentally measured data. This is followed by unraveling the pharmacokinetic profile of flurbiprofen, which demonstrates its poor solubility. Finally, we explore the ability of Brij-58 micelle to prevent the accumulation of flurbiprofen and disaggregate the self-associated drugs in the biological media. It is revealed that flurbiprofen can be spontaneously solubilized into the hydrophilic shell region of the micelle. Our findings provide theoretical guidance toward using computer simulation as a practical implement for pharmaceutical formulation engineering.