Abstract
Introduction: We have developed methods to simultaneously introduce chemoselective groups to hyaluronic acid (HA) that can be crosslinked and used for immobilization of various molecules. It is easy to switch the functionalities of obtained materials through orthogonal ‘click’ chemistries.
Methods: HA polymers were dually functionalized with hydrazide and thiol groups, or aldehyde groups. Different functional molecules such as bisphosphonate (BP) groups for mineralization or camptothecin (CPT) as anti-cancer drug can be linked to thiol groups. HA polymers were characterized by 1H, 31P NMR, and UV-Vis Spectroscopy. Characterizations of materials were performed using SEM, TEM, rheology, and colorimetric calcium assay.
Results and discussion: The functional polymers were successfully synthesized. They can form hydrogels within 1 min with HA-aldehyde polymer. BP groups showed high affinity to calcium ions and inorganic nanoparticle phases were observed within BP containing hybrid hydrogel. On the other hand, CPT-linked HA polymer via S-S bond can self-assembled into nanoparticles, and the release of the drug is triggered by the addition of reduce agents (e.g. dithiothreitol).
Conclusions: The use of orthogonal click modification opened a versatile way to prepare different kinds of HA based carriers with various functionalities by simple methods. The multifunctional HA polymers show high potentials to be used for drug delivery (pro-drug) or tissue regeneration (BP linked HA).