The Preparation Of 4-arm-PEG Hydrogel And Its Application In The Treatment Of Soft Tissue Injury

Soft tissue injury is a common disease,the morbidity of which is second only to the common cold.Soft tissue injury will cause tissue edema,pain,even cause functional disorders in the corresponding parts of body.Soft tissue injury will have a serious impact on daily life.In the treatment of soft tissue injuries,the local transdermal drug preparations have less damage to the gastrointestinal tract,liver and kidney function,and so on comparing with oral drugs.But the local transdermal drug preparations is not controllable and allergic.So it is very necessary to find a safer and more efficient technologies for local transdermal delivery.This study was aimed to designing a drug delivery system based on polyethylene glycol hydrogels,which combine physical therapy with drug therapy for local transdermal drug delivery to treat soft tissue injuries.The main research work is as follows:1.A drug delivery system based on polyethylene glycol hydrogel(PA/Fe3O4/DS hydrogel)was designed and prepared.When the amino group of 4-arm-PEG-NH2 reacting with the active ester of 4-arm-PEG-NHS,the PEG hydrogel is obtained by chemically cross-linking.And a small amount of agar is blended to prepare a PA hydrogel;superparamagnetic Fe304 nanoparticles with the same size was obtained by Poly(ethylene oxide)method,and was loaded into PA hydrogel to obtain PA/Fe3O4/DS hydrogel.SEM characterization shows that the hydrogel with porous network structure and the Fe3O4 nanoparticles were dispersed in it.2.In vitro and in vivo experiments showed that the PA/Fe3O4/DS hydrogel had good biocompatibility;in vitro and in vivo release experiments demonstrated that the hydrogel had a magnetic response release behavior;an animal model of soft tissue injury was established for animal experiments.The results of animal experiments demonstrated that the hydrogel drug delivery was superior to the commercially available DS ointment in the effect of magnetic field,and is better safe and more efficient.These results indicate that the PA/Fe3O4/DS hydrogel can achieve the synergistic therapy combining magnetic therapy with drugs.3.A drug delivery system based on polyethylene glycol hydrogel(DS@peg-PLGA/PEG hydrogel)was designed and prepared.The peg-PLGA microcapsules with high drug loading rates were prepared by rapid membrane emulsification method;loaded the microcapsules into PEG hydrogels for preparing DS@peg-PLGA/PEG hydrogel patches.The in vitro cytotoxicity test showed that the hydrogel had good biocompatibility;in vitro release experiments showed that the drug delivery system had an ultrasonic responsive release behavior;in vitro and in vivo transdermal release experiments showed that the drug delivery system was transparent under ultrasound Skin release ability allows transdermal delivery.These results indicate that DS@peg-PLGA/PEG hydrogel patch is expected to achieve synergistic therapy combining ultrasonic therapy with drugs.4.All above results confirmed the establishment of two smart drug delivery systems can responsive release diclofenac sodium.Both the two kinds of drug delivery systems use physical technology to promote the transdermal delivery of drugs,and serving as a synergistic function of physical therapy and drug treatment.They are expected to be used as a novel therapeutic tool for the treatment of soft tissue and other similar local injury diseases.