Preparation And Performance Evaluation Of Composite Gel Film Based On Chitosan/Sodium Alginate-Polyvinyl Alcohol

Objective:Based on the coating method,a kind of bilayer hydrogel wound dressing gel film was designed and prepared,which is safe and non-toxic and has the ability of absorbing liquid,excellent mechanical properties and remarkable antibacterial effect.Methods:Chitosan（CS）,Sodium alginate（SA）and Polyvinyl alcohol（PVA）,which are biocompatible,non-toxic and cheap in cost,were used as raw materials to prepare a bilayer hydrogel wound dressing.SA/CS（ACS）gel film was prepared by coating method with low cost and simple process.The effect of adding PVA on gel film forming was investigated.PVA/SA-CS（PACS）,SA-PVA/CS（APCS）and PVA/SA-PVA/CS（PAPCS）gel films were prepared.Through the evaluation of the appearances of the gel film and the investigation of the PVA model,the gel film with better film formation was optimized.PVA/SA-CS（PACS）and APCS（APCS）gel films with different mass ratios were prepared by coating method combined with freeze-thaw process.Then the appearances of PACS and APCS were evaluated,and the models of PVA were investigated.PVA/SA-PVA/CS（PAPCS）bilayer hydrogel film was prepared by mixing PVA with SA and coating on the first layer,and then coating on a layer of PVA/CS solution.Water content,swelling rate,water absorption and vapor transmission rate were used as performance evaluation criteria to investigate coating thickness,freezing time,thawing time and number of freeze-thaw cycles,and to select the best film forming conditions.First,PAPCS gel films with PVA:CS=1:1,2:1,3:1,4:1,5:1 were prepared.Then the physical properties of PAPCS hydrogel film were evaluated by gel fraction,water content,vapor transmission rate,swelling performance,water retention and mechanical properties.The structure and morphology of the hydrogel films obtained were then characterized by Fourier transform infrared spectroscopy（FTIR）and Scanning electron microscope（SEM）.Then,iodine loaded crosslinked cyclodextrin metal-organic framework（I₂@COF）was prepared by solvent method.The release of I₂@COF sustained-release particles and I₂@COF@PAPCS gel film in vitro was investigated using human wound exudate as the release medium.In order to evaluate the biocompatibility and in vitro bacteriostatic ability of PAPCS gel film,the hemolysis rate and in vitro coagulation index were used as evaluation indexes to investigate the compatibility of PAPCS gel film in contact with blood and its ability to promote blood coagulation.Finally,the antibacterial properties of PAPCS and I₂@COF@PAPCS in vitro were investigated by antibacterial experiments.Results:ACS gel film was prepared by coating method,but the forming was poor.After introducing PVA,the gel film forming capability was improved.PACS and APCS gel films with ratios of 1:4,1:2,1:1,2:1 and 4:1 were prepared,respectively.Compared with PACS,APCS had better morphology.APCS form a more complete gel film at PVA:CS=2:1 and 4:1.The effect of PVA on APCS film formation was investigated.Compared with PVA 1788 and PVA 1799,the gel film prepared by PVA1750±50 has better elasticity,weak adhesion and better film formation.Then,by mixing PVA with SA and CS respectively,with PVA/SA as the bottom layer and PVA/CS as the top layer,the PAPCS hydrogel film was successfully prepared.PAPCS are visible bilayer films with light yellow PVA/CS layer on the upper layer and white PVA/SA gel layer on the lower layer.The film forming process of PAPCS was determined as follows:coating thickness of 1.2mm,freezing time of 17 h,thawing time of 4 h,freezing and thawing cycles for 3 times.Then,PAPCS hydrogel films with mass ratio of PVA to CS of 1:1,2:1,3:1,4:1and 5:1 were prepared by coating method.The physical properties of hydrogel films were evaluated by measuring gel fraction,water content,vapor transmission rate and swelling rate.With the increase of PVA:CS ratio,the gel fraction increased,the crosslinking degree increased,and the water content decreased.The tighter structure of the gel film prevents the diffusion of water molecules,leading to the reduction of swelling rate and vapor transmission rate.When PVA:CS ratios were 1:1 and 5:1,the hydrogel film morphology was poor,so samples with ratios of 2:1,3:1 and 4:1 were preferred for subsequent experiments.The water retention rate results showed that the water retention rate of the hydrogel film with the ratio of 2:1 was significantly higher than that of the 3:1 and 4:1 groups in 0-4 h,and was better than that of the 3:1 and 4:1groups in maintaining its own water.However,compared with 2:1 hydrogel film,4:1hydrogel film has the maximum tensile strength of（0.61±0.08）MPa and 3:1hydrogel film has the maximum elongation at break of（189.56±10.57）%.The morphology of PAPCS hydrogel film was characterized by SEM.The PAPCS hydrogel film has a porous bilayer structure.The results of FTIR showed that PAPCS was a physical combination of PVA,SA and CS.The solvent method was used to prepare I₂@COF.The drug loading of I₂@COF was 21.91%and RSD were 1.01%by potentiometric titration.The in vitro release curve showed that the cumulative percentage of iodine released in I₂@COF particles and I₂@COF@PAPCS gel film reached 93.28%and 79.56%within 12 h.I₂@COF@PAPCS delayed the release of iodine in the particles to a certain extent.Blood compatibility experiments showed that the hemolysis rates of 2:1,3:1 and4:1 PAPCS were（4.16±0.42）%,（3.29±0.46）%and（1.49±0.30）%,respectively,and the hemolysis rates were less than 5%,indicating that PAPCS gel film had good blood compatibility.The evaluation of in vitro coagulation ability showed that PAPCS had a better ability to promote blood coagulation than PVA/SA,and 2:1 had the lowest BCI of（72.93±3.58）%,and this ratio of PAPCS had the best coagulation effect.The diameters of antibacterial zones of PAPCS and I₂@COF@PAPCS against E.coli were（12.28±0.25）and（18.89±0.81）mm,while that against S.aureus are（11.89±0.22）and（21.95±1.47）mm.PAPCS itself also has a certain bacteriostatic effect on S.aureus and E.coli,which is further enhanced when combined with I₂@COF.PAPCS bilayer hydrogel film dressing have been successfully prepared by coating method,and its various performance indexes are preferrable,with obvious coagulant and when combined with bacteriostatic effects,and I₂@COF,the bacteriostatic effect is further enhanced.Conclusions:Based on the electrostatic adsorption principle of CS and SA,PAPCS bilayer hydrogel film wound dressing with PVA/SA as the lower layer and PVA/CS as the upper layer was successfully prepared by coating method combined with freeze-thaw process.PAPCS hydrogel film has good swelling rate,vapor transmission rate,water retention performance,mechanical properties,blood compatibility.Its porous,stable three-dimensional structure is conducive to absorb wound exudates,maintain a breathable environment.Compared with PVA/SA,bilayer PAPCS hydrogel film has better coagulation ability and bacteriostatic performance,and the bacteriostatic effect is further enhanced after the combination of bacteriostatic composition I₂@COF.In brief,PAPCS bilayer hydrogel film has good performance and significant antibacterial and clotting effect,which can be used as an ideal wound dressing.