A new strategy for nanosuspension stabilizer screening based on computer-aided drug design and molecular self-assembly.

The aim of this study is to elucidate the principles of surfactants and polymer stabilized nanosuspensions (NS) from a molecular perspective, and to develop a new strategy for screening NS stabilizers based on molecular self-assembly. Through comparing the results of two virtual screening strategies (molecular self-assembly and molecular docking) and real experiments, it was found that molecular dynamics simulations -based molecular self-assembly could screen the stabilizers suitable for NS more accurately. Because, compared to the static binding molecular docking (MD) technique, molecular dynamics simulation (MDS) is able to simulate the nanoparticle formation process more realistically. This simulation not only captures the transient interactions between the stabilizer and the drug, but also observes their evolution in solution over a long period of time, thus providing a more comprehensive and dynamic perspective of the stabilizer screening process. This study established a link between microscopic simulations and macroscopic experiments, thus creating new avenues for rational formulation design. Compared with the traditional trial-and-error method, this new strategy dramatically reduces the range of stabilizer candidates through virtual screening, which can help researchers shorten the NS development cycle as well as cut R&D costs. In addition, microsimulation could provide important insights into how stabilizer-drug interactions determine the stability of NS.