Guanidine hydrochloride-induced transport mode transition of β-cyclodextrin-amantadine inclusion complexes revealed by a single α-hemolysin nanopore.

Abstract

Cyclodextrin inclusion complexes are widely used in drug delivery systems because they can improve the solubility and stability of drug molecules. However, the stability and transport mechanism of host-guest complexes during transport processes remain poorly understood. In this work, a single α-hemolysin (α-HL) nanopore was employed to investigate the host-guest interactions and dynamic transport behavior of β-cyclodextrin (βCD) and amantadine hydrochloride (Ad) in guanidine hydrochloride (GdnHCl) electrolyte. The results showed that GdnHCl significantly altered the kinetic behavior of βCD and its inclusion complexes within the nanopore. In the conventional KCl electrolyte, βCD-Ad complexes primarily exhibited a sequential transport mode involving dissociation prior to transport. In contrast, in GdnHCl electrolyte, βCD-Ad inclusion complexes entered the nanopore as intact host-guest assemblies and exhibited two transport pathways: in-pore dissociation after entry and translocation without detectable dissociation. The proportion of events involving intact host-guest assemblies increased significantly with increasing GdnHCl concentration, indicating that GdnHCl promotes the transport of inclusion complexes while maintaining host-guest association. Furthermore, a possible higher-order inclusion state was observed in 2.0 M GdnHCl, and the formation process of βCD-Ad complexes was monitored in real time. The fraction of βCD-Ad complexes exhibited a single-exponential growth behavior with an apparent growth rate constant of 0.058 min-1. These findings reveal the important role of the electrolyte microenvironment in regulating the stability and transport modes of cyclodextrin host-guest complexes, providing new insights into the transport mechanisms of supramolecular complexes and the design of advanced host-guest delivery systems.