Cyclodextrin Nanosponge-PVA Hybrid Networks as Supramolecular Reservoir Systems for Amitriptyline.

Poly-(vinyl alcohol) (PVA) hydrogels incorporating β-cyclodextrin (βCD) nanosponges (CDNSs) were developed as hybrid supramolecular systems for the controlled delivery of amitriptyline hydrochloride (AMT). The βCD-derived nanosponges provide host-guest cavities for drug inclusion, while the PVA network acts as a diffusion-regulating matrix. Initially, adsorption-desorption studies were performed on isolated CDNSs to evaluate their drug-loading capacity prior to incorporation into the hydrogels. The CDNSs exhibited efficient encapsulation (∼60%) and released more than 90% of the drug, confirming strong yet reversible host-guest interactions within CDs cavities. The drug-loaded CDNSs were subsequently dispersed in PVA solutions and physically cross-linked by freeze-thaw cycling, producing hydrogels containing embedded supramolecular reservoirs. Increasing the PVA concentration (from 14 to 20% w/v) generated denser polymer networks, reducing the swelling degree from ∼60 to ∼30 and slowing water uptake. CDNSs incorporation altered the hydrogel microstructure and introduced additional drug-matrix interactions, resulting in reduced burst release, measurable lag times, and more prolonged release compared with neat PVA hydrogels. Release kinetics were best described by the Weibull model, indicating diffusion-controlled transport in the pure matrices and heterogeneous diffusion behavior in the hybrid systems. Overall, AMT release is governed by coupled mechanisms involving diffusion through the polymer network and dissociation from cyclodextrin host sites, with CDNSs acting as supramolecular reservoirs within the hydrogel matrix.