| Bacterial dermatosis is a very important disease in dermatology.Staphylococcus aureus,Streptococcus,Propionibacterium acnes and Mycobacterium tuberculosis are common microorganisms that cause acute and chronic skin infections.Among them,Staphyloccus Aureus（SA）,as a microorganism with a high infection rate and a certain mortality rate,can not only cause clinical common acute skin infections such as folliculitis,furuncle,carbuncle and abscess,but also enter the bone marrow through skin to cause osteomyelitis,blood to cause sepsis and even death in severe cases.Therefore,effective anti-SA treatment is an important means to solve bacterial skin infection in early clinical stage.Mupirocin（Mup）has strong antibacterial activity against aerobic gram-positive cocci,especially against Staphylococcus aureus.Other antibacterial drugs such as erythromycin and fusidic acid,because of their oral or intravenous preparations,are not the choice of routine external medicine treatment.Mopirocin,as an antibiotic with only external dosage forms,is not prone to systemic drug resistance.Mopirocin is mainly used to prevent or treat local bacterial skin infection in clinic,but with the increasing clinical application of Mup,the resistance of SA to Mup is increasing year by year.This Mup-resistant SA is called Mu RSA,which will lead to the failure of local drug treatment.Therefore,there is an urgent need to develop a new type of external antibacterial agent to fight Mu RSA and obtain a new breakthrough in treatment.In this study,D-α-vitamin E polyethylene glycol succinate（TPGS）was used to modify mupirocin-silver complex（TPGS/Mup-Ag）to reverse the drug resistance of SA to mupirocin,so as to restore the killing effect of Mup on SA.In this study,Mup was complexed with silver to prepare Mup-Ag complex,in order to make silver ions cooperate with Mup to exert antibacterial effect and achieve stronger antibacterial activity.After being modified by TPGS,the particle size of the complex is smaller and more uniform,it is easier to be internalized by bacteria,and its bactericidal activity is stronger.In vitro drug release experiment results showed that the drug release rate of TPGS/Mup-Ag group was slower than that of TPGS/Mup group,which may be due to the slow dissociation of Mup-Ag complex in slightly acidic environment,thus gradually producing mupirocin,achieving sustained release effect and exerting sustained antibacterial effect.In this study,Mu RSA was used as the model strain,and the mouse model of infectious skin ulcer was established by subcutaneous injection.The wound was smeared with TPGS/Mup-Ag solution for 14 days.The results of the study on the bacterial load of skin showed that the bacterial content in the wound of mice decreased in different degrees after9 days of treatment with various preparations,and the bacterial content in the skin of mice decreased to the lowest level after TPGS/Mup-Ag treatment.The morphology of wound skin was analyzed,and it was found that the wound area decreased to 26%of the original area after 11 days of treatment,suggesting that TPGS/Mup-Ag can significantly accelerate the healing process of wound.Through histological analysis of infected mice,it was found that after TPGS/Mup-Ag treatment,the epidermis and dermis of mice recovered,and collagen fibers existed in subcutaneous tissue.Finally,the hemogram and weight of mice were analyzed,and it was found that after TPGS/Mup-Ag treatment,the white blood cell count,lymphocyte count and neutrophil count of mice returned to normal levels,and their weight gradually returned to normal state.In summary,the experimental results show that TPGS/Mup-Ag prepared in this study can effectively control the reproduction of Mu RSA caused by skin infection,inhibit the occurrence and development of inflammatory reaction and shorten the wound healing time.This study can provide a new idea for the development of antibacterial drugs modified by TPGS for the treatment of drug-resistant skin microbial infections. |
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