Self-healing low-molecular-weight hydroxamic acid hydrogel for active pharmaceutical ingredient formulation

<jats:p>Here, we report a hydroxamic acid-functionalised 1,3:2,4-dibenzylidenesorbitol hydrogelator (DBS-CONHOH), with a pKa value of 9.2 meaning that, unlike analogous carboxylic acid LMWGs, it forms stable gels at physiological pH. Perhaps surprisingly, given the favourable pH profile, low-molecular-weight gelators (LMWGs) based on hydroxamic acids are very underrepresented in the literature. The gel properties of DBS-CONHOH depend on the stimulus used to trigger gelation and are also sensitive to ionic additives. Importantly, unlike other DBS-based gels, DBS-CONHOH has thixotropic self-healing characteristics. This is most effective for gels formed by sonication, which creates gels underpinned by significantly shorter nanofibres, facilitating network healing. A variety of hydrophilic active pharmaceutical ingredients (APIs: Ldopa, rivastigmine tartrate, atropine sulfate and oxytocin) were formulated in these gels, with rapid release being observed. NMR methods provided insight into the interactions between APIs and the gel network, rationalising differences in release rate. The gels were cytocompatible with human mesenchymal stem cells, and we suggest these self-healing LMWG hydrogels may have future potential for (e.g.) intranasal or intraocular drug delivery.</jats:p>