Evaluation Of Drug Efficacy Of Porous Silicon Nanoparticle Drug Delivery System In Mice Model Of Inflammatory Bowel Disease

Inflammatory bowel disease(1BD)is a type of nonspecific intestinal inflammatory disease.In the past,IBD often occurred in developed countries,however,the incidence of IBD in developing counties has also shown an obvious increase in recent 20 years.The hospitalization rate and surgical rate of IBD have remained high,what’s more,IBD may lead to the occurrence of intestinal malignant tumors,which have greatly affected the quality of life and life expectancy of patients.The development of effective therapy for IBD has become one of the research hotspots for gastrointestinal diseases.Due to the limitations of the common drug formulations and the special environment of the gastrointestinal tract,the conventional oral drugs fail to treat IBD effectively.Therefore,to develop drug carrier that can be specifically accumulated at the site of inflammation and released the drug for the treatment of inflammation is highly demanded.In this thesis,we have investigated the efficacy of improved porous silicon nanoparticles as drug carriers for the treatment of IBD in collaboration with Professor Santos in the University of Helsinki,Finland.First,we established the model of colitis with DSS in C57BL/6 mice.Secondly,the in vivo fluorescence imaging and immunofluorescence staining were used to prove that the porous silicon nanoparticles can be specifically concentrated at the injury sites of the intestine in mice.Afterwards,mice were given various types of drug-loaded porous silicon nanoparticles at varied dosages by oral administration.Finally,the efficacy was evaluated after the drug treatment for xx days.The disease activity index showed that the mice treated with the modified drug-loaded porous silicon nanoparticles had the best gastrointestinal recovery among these experimental groups.The pathological analysis of mouse colons using HE staining also demonstrated that the improved drug-loaded porous silicon nanoparticles exhibited better therapeutic effect.TUNEL staining indicated an obvious decrease in the ratio of apoptotic cells in the injured part of the mice treated with the modified drug-loaded porous silicon nanoparticles.The results of ELISA assays of inflammatory factors in mouse plasma also proved that the improved drug-loaded porous silicon nanoparticles can reduce the release of IL-6 and IL-1β in vivoIn summary,using the DSS-induced IBD mouse model,we have systematically evaluated the therapeutic effect of the modified drug-loaded porous silicon nanoparticles.These results showed that the improved drug carrier has a better efficacy in the treatment of inflammatory bowel disease.It has been demonstrated that the newly designed system of pH and enzyme sequencially response to drug delivery provides a more effective therapeutic approach for IBD.