Nanostructured hyaluronic acid-based hydrogels encapsulating synthetic/natural hybrid nanogels as promising wound dressings

Hydrogels with nanostructured morphology formed by embedding polymeric nanoparticles in a biodegradable polymer matrix have gained considerable interest in the medical field due to improved drug delivery profiles and tissue-mimicking architecture. Moreover, through hydrogels biodegradation, the encapsulated nanoparticles are released and can easily enter in different compartments of the body, thus having the potential to control the delivery of short half-life drugs. Therefore, this study was devoted to preparation and characterization of nanostructured hybrid hydrogels by incorporating well-defined maleoyl-chitosan/poly(aspartic acid) (MAC5/ PAS) nanogels into a polymer network based on thiolated hyaluronic acid (HASH) for wound dressings applications. The MAC5/PAS nanogels were used not only as nanocarriers for amoxicillin (Amox) encapsulation and control over its release through the HASH hydrogel network, but also as building blocks for hydrogel preparation. The obtained nanocomposite hydrogels exhibited a reduced swelling capacity and a controlled degradation rate in comparison with the non-filled HASH hydrogel. In vitro release profile revealed the influence of environment pH on Amox delivery, a rapid release of drug being observed at pH 5.4. Moreover, the in vitro and in vivo assays revealed a good biocompatibility of hydrogels, highlighting the potential of these systems as therapeutic scaffolds for dressing applications.