Advancing the biphasic drug delivery system through the molecular encapsulation of pinocembrin with NO-releasing β-cyclodextrin derivatives: A computational insight

Comprehending the intricate interactions between pinocembrin (PNCB) and NO-releasing β-cyclodextrin is fundamental for advancing novel gas-solid biphasic drug delivery systems (DDSs). Theoretical methods, including molecular dynamics (MD) and density functional theory (DFT) calculations, were utilized to investigate the structural stability and interaction mechanisms of inclusion complexes formed between PNCB and two β-CD derivatives: mono-6-diethylenetriamine-β-cyclodextrin (D-β-CD) and mono-6-ethylenediamine-β-cyclodextrin (E-β-CD). Two favorable conformations for PNCB inclusion within β-CD derivatives were identified: the benzene ring insertion (Conf-P) and the chromone ring insertion (Conf-C). MD simulations confirmed that the inclusion complexes of PNCB with NO-modified β-CDs exhibit excellent stability and encapsulation efficiency, with Conf-C demonstrating superior efficacy. DFT analysis revealed that dispersion interactions govern host-guest molecular interactions, and D-β-CD emerged as the most effective carrier for PNCB due to the formation of strong hydrogen bonds. These outcomes offer a fundamental understanding of PNCB@β-CDs complexes, paving the way for developing advanced biphasic DDSs based on NO-releasing β-CD derivatives.