A novel injectable in situ forming gel based on carboxymethyl hexanoyl chitosan/hyaluronic acid polymer blending for sustained release of berberine

An in situ forming gel based on simply blending carboxymethyl hexanoyl chitosan (CHC) with low molecular weight hyaluronic acid (LMW HA) was developed, without needing cross-linking, photopolymerization or thermal treatments. The CHC/LMW HA blends formed nanoparticles and then rapidly transformed into super-molecular hydrogels under stirring. The gel formation mechanism was examined by Forster resonance energy transfer (FRET). The gels were injectable, cytocompatible and biodegradable, and showed shape-persistent behavior and adhesive property. Berberine, an anti-apoptotic and anti-arthritis naturally occurring compound, was encapsulated within the CHC/LMW HA gels. The gels demonstrated a pH-responsive characteristic which were able to release berberine in a sustained manner at pH 6.0 (simulating inflamed arthritic articular cartilage) and the degradation rates were accelerated at pH 7.4 (simulating healed normal tissue). The berberine-loaded gels effectively protected chondrocytes against sodium nitroprusside-induced apoptosis. The gels may be potentially useful as an injectable system for intra-articular drug delivery and cartilage tissue engineering.