Supramolecular Hydrogels for Drug Delivery Applications

Low molecular weight gelators (LMWGs) form gels through a series of non-covalent interactions, creating a network that traps solvent, preventing flow. Due to the reversible nature of the interactions, these materials are typically highly responsive to external stimuli, making them attractive for high-tech applications, particularly in the biomedical field. Despite significant progress in this area, it is still challenging to design a gelator with the required properties for an application from scratch. This research therefore aims to develop novel materials, focussing on drug delivery applications, exploiting multiple strategies to achieve this. We initially focussed on the dibenzylidene sorbitol derivative DBS-CONHNH2, a hydrogelator capable of interaction with additives – but mechanically weak. This was therefore combined with a novel hydrogelator MBS-CO2Me – which increased the robustness of the material. Both the mechanical and thermal properties could be tuned by varying the proportions of the two gelators. Additionally, the gel was capable of pH responsive release of naproxen, as well as encapsulation and release of atorvastatin. The impact of sugar chirality on the behaviour of the gelators was then investigated, with DBS-CONHNH2 synthesised using the ʟ-sorbitol in place of the natural ᴅ sugar. This was shown to have the same properties as the ᴅ-DBS-CONHNH2, as would be expected, with the exception of response to polarised light. The effect of encapsulating chiral additives within each enantiomer was then investigated, with small effects on the properties of the materials observed. Finally, further characterisation of a previously reported gelator, based on glutamine amide, was carried out – with particular attention paid to the self-healing rheological properties of the gel. This investigation was carried out both for the gel alone, and for the gel with L-DOPA incorporated. As part of a collaboration, these gels were tested in early stage in vivo, for nasal delivery of L-DOPA to the brain, as a treatment for Parkinson’s Disease. These early-stage tests indicated promise of these hydrogels as delivery vehicles for delivery of active agents to the brain.