Effects Of Lidocaine-loaded Carboxymethyl Chitosan Cross-linked With Sodium Alginate Hydrogels For Drug Delivery System,Cell Adhesion,and Pain Management

Objective In this work,carboxymethyl chitosan(CCS)cross-linked with sodium alginate(SA)hydrogels loaded with or without lidocaine(LID)are prepared.The physicochemical and mechanical properties of developed CCS-SA hydrogels are evaluated.At the same time,both the vitro cytotoxicity,vivo toxicity effects,vitro skin permeation efficiency and vivo anesthetic efficacy are also tested.This result providing a possible route to developing long-lasting local anesthetics that might be employed as a therapeutic pain management alternative.Methods CCS-SA loaded with or without lidocaine was made using a modification of a previously used approach.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.The entrapment of LID is confirmed by measuring encapsulation efficiency and monitoring drug loading.The drug release studies are conducted by immersing the LID-loaded CCS-SA hydrogels in PBS with different pH values to investigate their potential for being used as pH-responsive materials for oral drug delivery applications.Cellular viability and cell attachment of Balb-c 3T3 cells are measured by MTT,FM and SEM analysis separately to evaluate the cytotoxicity of CCS-SA loaded with lidocaine.We are valuate the skin permeability of CCS-SA hydrogels by IVPT.We evaluated the vivo anesthetic efficacy of the LID-loaded CCS-SA hydrogels through TFL.Through H&E,observe the inflammatory reaction of local skin and the photographs of tissue slices,and evaluate the anti-inflammatory effects and the vivo cytotoxicity of LID-incorporated CCS-SA hydrogels.Results CCS-SA hydrogels has outstanding swelling resistance,vitro degradation and mechanical stability.The results of the FTIR spectrum show that,Because the amino groups in CCS cross-linked with the hydroxyl groups in SA,the mechanical characteristics of the CCS-SA hydrogels are improved.Results of XRD pattern show that the CCS-SA hydrogels have an amorphous structure.And the results of SEM show that it has a typical 3D porous structure.The LID-loaded CCS-SA hydrogels are found with the highest encapsulation efficiency of 92.9 ±2.26%and the DL is about 7.53±0.75%,show that it has a best LID encapsulation in CCS-SA hydrogels.The results of drug release studies show that the LID is released differences in PBS at various pH values which approve their potential for being used as pH-responsive materials for oral drug delivery applications.The results of MTT assay show that the LID-loaded CCS-SA hydrogels are found to be non-cytotoxic to Balb-c 3T3 cells at concentrations below 100 μg/ml.FM and SEM images show outstanding cell attachment performance of the Balb-c 3T3 cells attached to the LID-loaded CCS-SA hydrogels.The results of IVPT show that the LID-loaded CCS-SA hydrogels are able increased the drug absorption through the skin compared to free LID drug.The TFL results show that the CCS-SA hydrogels composition demonstrates s considerable increase in anesthetic duration and maximal efficacy,when contrast to the free LID.H&E-stained images show that the CCS-SA hydrogels loaded with or without lidocaine both decrease local tissue damage and has no substantial cytotoxicity in vivo.Conclusion 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.