Construction And Study On Renal Fibrosis Repairment Of Cationic Polymer Drug Delivery Nano System

In recent years,nanodrug-delivery systems in biomedical application have been attracted widely attention.At present,poly(lactide-co-glycoside)(PLGA)nanoparticles(PLNPs)are extensively applied in the field of drug delivery due to its good biocompatibility,biodegradability,easy surface modification and diverse loaded drugs.The incidence of chronic kidney disease(CKD)has garadually been increased in recent years.CKD develops to end-stage renal disease(ESRD),which requires kidney replacement or dialysis.And renal fibrosis will gradually proceed throughout the progress of CKD.However,the poor stability in vivo,low cellular uptake efficiency,inappropriate distribution and unwanted side effects of the drugs for renal fibrosis greatly limits its clinical applications.So far,there are still no effective drugs or therapy strategies to reverse the progress of renal fibrosis.Therefore,the development of a kidney targeting drug delivery system has great significance for high-efficiency anti-fibrosis treatment.Based on the excellent properties of PLNPs,nanodrug-delivery systems(i.e.,low molecular weight chitosan modified PLNPs(PCNPs)and polyethyleneimine(PEI)modified PLNPs(PENPs))were prepared by nanoprecipitation method.And the targeted therapy of PCNPs and PENPs for renal fibrosist have been investigated through constructing cell fibrosis and unilateral ureteral ligation(UUO)models.Major results of this thesis were as follows:1.Different sizes of PLNPs and PCNPs were prepared by nanoprecipitation method,and PCNPs were used to load miRNA-21 inhibiror(miRi)for renal fibrosis treatment.The studies showed that PCNPs could improve the stability and transfection efficiency of miRi,and possessed good biocompatibility and kidney targeting.2.The evaluation of PCNPs loaded with miRi(miRi-PCNPs)on the cell and UUO renal fibrosis model showed that miRi-PCNPs had higher therapeutic efficiency compared with free miRi.And further studies found that miRi-PCNPs could suppress the TGF-?1/Smad3 and ERK/MAP kinase signaling pathway by inhibiting the expression of miRNA-21,thus achieving an effective treatment for renal fibrosis.3.Renal-targeting PENPs were prepared by modifying PLNPs with PEI.And our studies found that PENPs had better biocompatibility and higher cellular uptake efficiency than PLNPs.In addition,PENPs also possessed drug released and kidney targeting ability.