Journal
CARBOHYDRATE POLYMERS
Volume 206, Issue -, Pages 664-673Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2018.11.050
Keywords
Chitosan; Hyaluronic acid; Injectable hydrogels; Berberine; Drug delivery
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Funding
- Ministry of Science and Technology [MOST 106-2221-E-038-015-MY2, MOST 106-2320-B-019-002-MY3]
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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.
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