Local anesthetic effects of lidocaine-loaded carboxymethyl chitosan cross-linked with sodium alginate hydrogels for drug delivery system, cell adhesion, and pain management

Abstract

The development of hydrophilic carriers for drug encapsulation represents a current challenge. In this work lidocaine (LID) loaded with carboxymethyl chitosan (CCS) cross-linked with sodium alginate (SA) hydrogels were prepared to achieve the controlled release of LID drug. The mechanical characteristics of the CCS-SA hydrogels were examined via the swelling ratio, in vitro degradation, and rheological analysis. The as-prepared CCS-SA hydrogels were characterized by FTIR, XRD, and SEM analysis. The morphology of the CCS-SA hydrogels composites was confirmed porous structure. Satisfactory encapsulation and release characteristics were obtained for the LID-loaded CCS-SA hydrogels. Cytotoxicity assays test on Balb-c 3T3 cells confirmed that the LID-loaded CCS-SA hydrogels reduced its toxicity, relative to the free LID drug. The live/dead cell assay showed that the LID-loaded CCS-SA hydrogels using cell encapsulation study are nontoxic and cytocompatible toward Balb-c 3T3 cells. The anesthetic efficacy of LID-loaded CCS-SA hydrogels was evaluated using Balb/c mice. When administered in inflamed areas, LID-loaded CCS-SA hydrogels emerged as having stronger and longer analgesic effects. The measurement of CCS-SA hydrogels loaded with LID intravenously to tumor-bearing mice demonstrated active targeting in tumor tissues 24 h after injection. Based on these results, it appears that LID-loaded CCS-SA hydrogels have a local anesthetic effect that can effectively reduce injection times for postoperative pain management and limit the adverse effects of anti-inflammatory drugs.