Abstract
Local anesthetics have been extensively used in clinical practice to relieve the postoperative pain of patients. However, due to the short half-life of local anesthetics, a simple injection of local anesthetics cannot provide sufficient anesthetic effect for patients. It is important to develop a new delivery system for local drug administration to achieve an extended anesthetic effect without notable side effects. In this study, bupivacaine hydrochloride (BPV) loaded thermosensitive hydroxypropyl chitin (HPCH) based sponges were prepared via a simple solvent-free process for long-lasting drug release. The HPCH sponge showed good mechanical property to resist external stress and maintain the integrity, which was stronger than the collagen/HPCH composite sponge and much better than the pure collagen sponge. The HPCH sponge also displayed good biodegradability and compatibility. The BPV-loaded 2.4%-HPCH (3.6 wt%) sponge showed the most sustained release profile, and the maximal duration of in vitro release was about 8 times longer than that of the control group BPV-loaded 0.8 %-collagen (0.6 wt%) sponge based on commercial Xaracoll. More importantly, the effective duration of blockade (analgesia) of 21.67 h for the BPV-loaded 2.4 %-HPCH (3.6 wt%) sponge was much longer than that of the bupivacaine hydrochloride solution injection (1 h, 0.8 %-BPV solution) in the guinea pig pin-prick test. Hematoxylin-eosin staining data indicated that a very limited mild inflammatory response was observed at the location where the BPV-loaded HPCH (3.6 wt%) sponge was placed. Thus, the HPCH sponge is expected to serve as a promising drug carrier for the sustained release of bupivacaine in postoperative pain management.
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