Silicate Clay-Hydrogel Nanoscale Composites for Sustained Delivery of Small Molecules

Hydrogels have been widely used for therapeutic delivery applications due to their tunability and biocompatibility, although delivery of small molecules is difficult due to high burst release and rapid diffusion from the device. Nanosilicate clays (nanoclays) have shown the adsorption potential of small molecules, offering a lever to prolong the release kinetics of hydrogel delivery devices. However, further characterization of small molecule–nanoclay interactions and their effect on molecule release is needed to allow for the custom design of tunable nanocomposite hydrogel delivery devices. Here, we have characterized the adsorption of small molecules onto three nanoclays, Laponite, montmorillonite, and halloysite, and monitored their release in various conditions. The layered structures of Laponite and montmorillonite led to cationic exchange of the small molecules into the interlayer space, whereas the small molecules were adsorbed onto the surface of the tubular halloysite. The addition of nanoclays to polyethylene glycol (PEG) hydrogels significantly slowed the release of small molecules, especially from Laponite (500-fold decrease) and montmorillonite (∼3000-fold decrease) composite gels. Cationic small molecules were shown to be released significantly slower from nanocomposite hydrogels than anionic ones. The incubation time of small molecules with nanoclays prior to hydrogel encapsulation also played a key role in determining their release rate, with montmorillonite showing near-immediate adsorption while halloysite exhibited a higher dependence on incubation time due to slower adsorption kinetics. Release buffer salt concentration and pH were shown to affect release kinetics due to modulation of nanoclay–small molecule interactions. These results show the potential for formation of a highly tunable nanocomposite hydrogel delivery device for a greatly prolonged release of small molecules compared to traditional hydrogels.