Work performed from the beginning of the project to the end of the period:
Light sensitive supramolecular hydrogels, that allow long-term and on-demand release of therapeutics into the vitreous for the treatment of posterior eye disorders, were designed, synthesized and characterized. The properties of the light sensitive supramolecular hydrogels, including microstructure, rheology, stability, injectability and ability to controllably release loaded cargos, were confirmed and the bioactivity (therapeutic effect) of the loaded cargos was assessed in an in vitro model of angiogenesis. Therapeutic peptides with reported anti-angiogenic activity were synthesized and modified to drive their self-assembly into stable nanostructures. Their integration in light sensitive supramolecular hydrogels was attained by investigating their interaction with the hydrogel components. Using an established in vitro model of angiogenesis, the anti-angiogenic effect of the hydrogels containing therapeutic peptides was investigated.
Description of main results achieved so far:
A light-sensitive supramolecular hydrogel was successfully developed as designed and its rheological properties, injectability, both in solution and in an ex vivo ocular model, were characterized. The hydrogel can be easily injected, being stable in both phosphate buffer saline solution (pH 7.4) and in the vitreous humour. The supramolecular hydrogel was shown to have a high loading capacity for a model protein and its light sensitivity is able to regulate the release of the model protein up to 30 days. This result indicates the possibility to use this hydrogel for the delivery of other macromolecular proteins, such as antibodies used clinically. In addition, a series of anti-angiogenic peptides, as well some peptide variations, were successfully synthesized and their interactions with the hydrogel components studied. Peptides with aromatic residues were found to generate stronger interactions with the hydrogel components. The interaction between hydrogel component and the peptides was shown to be beneficial, not only by reducing their cytotoxicity, but their combination in the hydrogel also generated a stronger anti-angiogenic effect compared to the peptide alone. These results show that the interaction between hydrogel component and peptides can affect the way in which these peptides originally act on cells, which is worthy for further research to develop new clinical treatment methods with small molecules.
We have attended several workshops and international conference to introduce our ocular delivery platform. In addition, a review paper entitled Supramolecular Hydrogels for Protein Delivery in Tissue Engineering was published to discuss the importance of supramolecular hydrogels as delivery system.
