Poly (n-butyl cyanoacrylate) as a nanocarrier for rivastigmine transport across the blood-brain barrier in Alzheimer's disease treatment: a perspective from molecular dynamics simulations.

In this study, molecular dynamics simulations have been used to investigate the behavior of the drug rivastigmine and its carrier so-called poly (n-butyl cyanoacrylate) in the encapsulation process. Polymer modeling, and subsequently the emulsion polymerization model, were applied to analyze drug release in vitro and to justify rivastigmine transport across the blood-brain barrier (BBB) and polymer agglomeration. On the other hand, suitable polymer chain length, encapsulation method, polarity between polymer and drug structure, and finally, pattern of drug released in vitro and in vivo have been investigated to analyze the behavior of drug and polymer accurately. Maximum drug loading was determined based on the modeling of drug encapsulation and comparison of the radius of gyration of polymer (Rg) and distance between center of masses (COMs) of rivastigmine molecules and polymer in equilibrium condition (A°). With the aim of better understanding of drug release, we calculated the Flory-Huggins interaction parameter, diffusion coefficient, and intermolecular interaction energy. The results reveal that more drug molecules remain on the surface of the polymeric structure, with increasing the concentration of rivastigmine molecules from 3 up to 7, but the number of encapsulated drug molecules inside of the polymer remains constant. Also, calculated values of Gibbs free energy indicated that intramolecular interactions of the polymer chain overcome the intermolecular interactions between polymer and drug. Therefore, any extra loading of drug resulted in accumulation on the polymer surface. Graphical abstract Poly (n-butyl cyanoacrylate) containing rivastigmine molecules.