PLGA Biomaterials Based Construction Of Antibacterial Delivery System And Treatment Strategy

Infection or inflammation caused by pathogens can cause high mortality.For instance,instance,invasive fungi,bacteria and highly infectious viruses,which poses a serious threat to the health and safety of many patients,especially those with immunodeficiency.Therefore,infectious diseases caused by pathogens are a global health problem.Currently,the treatment of infectious diseases caused by pathogens faces numerous challenges,such as relatively single treatment methods,lack of effective drugs,low drug safety,easy to cause side effects,abuse of antibiotics causing large numbers of drug-resistant bacteria.In addition,current treatment options for inflammation therapy in clinical are challenging to target deliver drugs to the inflammation,leading to high/frequent dosing and side effects.Targeting the inflammation to improve the efficacy,while reducing the dosage and side effects remains elusive in clinical treatment.Further efforts are still demanded to develop targeting delivery systems for modulating and reducing the local inflammatory responses in pneumonia.In this paper,taking fungal infection as an example,we aiming at major challenges in the treatment of fungal infection.We designed two effective delivery strategies to inhibit fungal infection.Thesis work is divided into the following two parts1.We found the enrichment effect of the injured wound tissue in the mouse model Based on this effect,we developed a targeted delivery strategy using nanomaterials to treat infection in wound.In this work,we found that the polymer nanoparticles injected intravenously could significantly enrich in the site of wound.The research indicated that the mechanism of this enrichment phenomenon is due to the histamine released from the inflammatory tissue that cause temporary dilation and leakage of the blood vessels,leading to the injection of nanoparticles through the blood vessels to reach the inflammatory site.Then,the potential mechanism of polymer nanoparticles enrichment in damaged tissue was studied.Hence,we propose a new mechanism of nano drug targeting wound,we further demonstrate targeted-delivery of anti-inflammatory agents by nanoparticles in the treatment of infection.2.We developed a local delivery strategy based on microneedle delivery system for antibiotic local delivery.Compared with traditional drug delivery methods,such as,injection and oral administration,transdermal administration can avoid the pain caused by needle penetration into the deep skin.The drug absorption rate could be greatly reduced by the first pass effect of liver,and its effect is affected.Transdermal administration owns its unique advantages,for example,painless,minimally invasive,safe and efficient,easy to carry,patients use by themselves,and macromolecular drugs can be delivered directly to the focus through the skin,which will greatly improve the absorption of the drug and reduce the toxic and side effects of the drug.Consequently,we designed a drug delivery strategy based on microneedle patch,which was applied to the mouse model of fungal infection,and achieved great therapeutic effect.To sum up,we designed two antifungal treatment strategies,that is,the nanoparticel-based passive targeted drug delivery strategy and the local transdermal administration strategy,and carried out the relevant experimental studies in the mouse model.All of which achieved certain results.Our strategy provides new ideas and insights for further clinical improvement of the treatment of infection or inflammation caused by pathogens.