Boronate-ester crosslinked hyaluronic acid hydrogels for dihydrocaffeic acid delivery and fibroblasts protection against UVB irradiation

Abstract

Herein, we exploit the dynamic nature and pH dependence of complexes between phenylboronic acid and diol-containing molecules to control the release of an anti-photoaging agent, dihydrocaffeic acid (DHCA), from a dynamic covalent hydrogel (HG). The HG is prepared by reversible formation of boronate ester crosslinks between hyaluronic acid (HA) modified with saccharide (GLU) residues and HA functionalized with 3-aminophenylboronic acid (APBA), part of which is involved in complexation with DHCA. The hydrogel exhibited increased dynamic moduli and a lower relaxation time at pH 7.4 in comparison to pH 6, and greater amount of DHCA was incorporated at pH 7.4. Moreover, this hydrogel prolonged DHCA release at pH 7.4 through drug reversible complexation/decomplexation, while the rate of release was fastest in acidic (skin) conditions. Very interestingly, the incorporation of DHCA into the network enhances its protection against UVB-induced L929 fibroblast death. Therefore, this smart hydrogel can contribute to photoaging prevention.