| ObjectiveNano silver nanoparticles have been widely used because of their high anti-infection activity due to its nano size.However,it is not suitable for direct administration because of its potential harm to human beings.In this study,silver loaded microspheres were prepared by ionic cross-linking method and loaded onto hydrogels prepared by glutaraldehyde as crosslinking agent.Its properties,biological safety and antibacterial properties are investigated,providing a basis for clinical application in the future.MethodsWith carboxymethyl chitosan as raw material,nano silver as model drug,sodium tripolyphosphate as crosslinking agent,silver loaded microspheres were prepared by ionic cross-linking method.Nano silver microspheres were added into carboxymethyl chitosan-glutaraldehyde hydrogel to prepare carboxymethyl chitosan hydrogel loaded nano silver microsphere.The drug encapsulation efficiency and particle size should be measured.The effect of carboxymethyl chitosan concentration and crosslinking agent concentration on swelling rate was determined.The release of nano silver in the preparation was determined by UV spectrophotometry.The biological safety of the sample was evaluated by delayed type hypersensitivity test,rabbit skin stimulation test and cytotoxicity test.The inhibition effect of the drug delivery system on Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa was detected by bacteriostatic ring test.The anti-infection effect of the drug delivery system was tested by rabbit as experimental animal model.Results1.Through the orthogonal design,preparation technology was optimized.The optimum conditions was that the carboxymethyl chitosan concentration of 4.2mg/ml,speed of 5 s/drops,the best dosage of nano sliver for 2 mg(500 μl).Under the condition of this experiment,the mean size of the silver loaded microspheres was514.1 nm with the polydispersity index of 0.204,the encapsulation efficiency was61.67%.2.When the concentration of glutaraldehyde solution was 1% and the concentration of carboxymethyl chitosan was 20 mg/ml,the swelling rate of hydrogel was the highest.The cumulative drug release of the system was 80% in p H 8.5 buffer solution for 24 hours.The hydrogel loaded nano silver had good release properties and p H sensitivity.3.In biological safety test,there was no erythema and edema in the skin of guinea pigs.There was no irritation to the back skin of rabbits.The cytotoxicity was grade 2.The carboxymethyl chitosan hydrogel loaded nano silver microspheres has good biocompatibility and biological safty.4.The antibacterial ring experiment results showed that the carboxymethyl chitosan hydrogel loaded nano silver microspheres had good antibacterial effect on Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa which were easy to grow on the wound surface.5.The test of anti-infective effect in vivo showed that the content of TNF-α and BET in the carboxymethyl chitosan hydrogel loaded nano silver microspheres group were always lower than those in the blank group in 24 h.Compared with the Banger Jie nano silver antibacterial hydrogel group(the positive control group),the TNF-αcontent of the wound in the carboxymethyl chitosan hydrogel loaded nano silver microspheres group was slightly higher than that in the positive control group at 5h,which was significantly lower than that in the positive control group subsequently.At the same time,the BET content in the positive control group increased significantly with the prolongation of the contact time,while the BET content in the carboxymethyl chitosan hydrogel loaded nano silver microspheresgroup did not increase with the prolongation of the injury time.ConclusionThe experimental results showed that the drug delivery system had slow-release function,p H sensitivity and better anti-infection effect.At the same time,it improves the duration of action and reduces toxicity.It has a certain application prospect in anti-infection,and has novel and practical in dosage form selection. |
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