Sistemas híbridos supramoleculares utilizando ciclodextrinas para liberação de cloridrato de amitriptilina

Abstract

Amitriptyline hydrochloride (AMT) is a tricyclic antidepressant used in the treatment of depression; however, it presents several side effects associated with oral administration, in addition to limited bioavailability. In this context, hybrid drug delivery systems based on supramolecular interactions with cyclodextrins (CDs) have emerged as promising strategies to modulate drug release and mitigate these limitations. These systems combine CD-based compounds, such as inclusion complexes (ICs) and cyclodextrin-based nanosponges (CDNSs), with biocompatible polymeric matrices. In this study, the interactions between AMT and different natural and modified CDs were investigated. Solid-state ICs were obtained by lyophilization and characterized by Fourier-transform infrared spectroscopy in attenuated total reflectance mode (FTIR-ATR). In solution, the interactions were evaluated by isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR) spectroscopy. ITC results indicated higher affinity and stability for the AMT:βCD system, while NMR experiments confirmed the inclusion compound formation, justifying the selection of βCD as a precursor for CDNS synthesis. Two CDNSs were prepared using hexane-1,6-diamine (am6) and dodecane-1,12-diamine (am12) as crosslinking agents. The CDNSs were characterized using spectroscopic, thermal, and colloidal techniques. AMT incorporation was confirmed by adsorption assays and scanning electron microscopy (SEM), and desorption studies demonstrated that more than 90% of the drug was released in water. Poly(vinyl alcohol) (PVA) hydrogels were used as polymeric matrices, and different polymer concentrations were evaluated in terms of morphology, swelling behavior, and release kinetics. Hybrid systems containing CDNSs incorporated into 20% PVA hydrogels exhibited a reduction in the burst effect and prolonged AMT release, demonstrating the potential of these materials as controlled drug delivery systems.