Magnetically responsive hydrophobic pockets for on–off drug release

The vast majority of drugs available on the market are hydrophobic compounds. As a result, their poor water solubility can critically compromise the overall absorption of these drugs by patients. Although numerous different strategies have been developed to improve their bioavailability, the controlled delivery of these drugs is still a challenge. In this sense, stimuli-responsive hydrogels could be a solution to improve administration and stable release. However, the strategies required to render hydrogels hydrophobic mostly rely on weak hydrophobic interactions, which can lead to disassembly of the system and undesired burst discharge. Accordingly, the on-demand release of poorly water-soluble drugs is still a major milestone in this field. To circumvent these setbacks, we present for the first time a hydrophobic, magnetically responsive hydrogel based on the diaminotriazine (DAT) skeleton. The versatility of DATs in terms of H-bond formation and metal complexation simultaneously endows the hydrogel with hydrophobicity and magnetic responsiveness, thus allowing both the efficient loading and on–off release of a model hydrophobic drug as well as of a hydrophobic bioactive substance. Theoretical calculations further suggested stable formation of DAT aggregates that operate as efficient hydrophobic cavities or ‘pockets’ for these compounds. Moreover, these materials were found to be suitable for enhancing the viability and growth of cell lines often used as in vitro models of neuronal function and differentiation. The present magnetic hydrogels hold interesting potential for tissue engineering as biocompatible scaffolds for the on-demand release of hydrophobic compounds, which remains the focus of current research efforts.