Design and evaluation of glomerulus mesangium-targeted PEG-PLGA nanoparticles loaded with dexamethasone acetate  

作　　者：Sha Li Ying-chun Zeng Ke Peng Chang Liu Zhi-rong Zhang Ling Zhang 

机构地区：[1]Key Laboratory of Drug Targeting and Drug Delivery Systems,Ministry of Education,West China School of Pharmacy,Sichuan University,610041 Chengdu,China [2]College of Polymer Science and Engineering,Sichuan University,610041 Chengdu,China

出　　处：《Acta Pharmacologica Sinica》2019年第1期143-150,共8页中国药理学报（英文版）

基　　金：the National Natural Science Foundation of China (Nos. 81473169 and 81130060).

摘　　要：Mesangial proliferative glomerulonephritis (MsPGN),one of the most common glomerulonephritis pathological types,often leads to end-stage renal disease over a prolonged period.But the current treatment of MsPGN is non-specific and causes serious side effects,thus novel therapeutics and targeting strategies are urgently demanded.By combining the advantages of PEG-PLGA nanoparticles and the size selection mechanism of renal glomerulus,we designed and developed a novel PEG-PLGA nanoparticle delivery system capable of delivering dexamethasone acetate (A-DEX)into glomerular mesangium.We determined that 90 nm was the optimum size to encapsulate A-DEX for glomerular mesangium targeting based on the size-selection mechanism of glomerulus. After intravenous administration in rats,90 nm DiD-loaded NPs were found to accumulate to a greater extent in the kidney and kidneycortex compared with the free DiD solution.The 90 nm A-DEX NPs are also more stable at room temperature and showed a sustained release pattern.In rat glomerular mesangial cells (HBZY-1)in vitro,we found that the uptake of 90 nm A-DEX NPs was both temperature-dependent and energe-dependent,and they were mostly engulfed via clathrin-dependent endocytosis pathways,in summary,we have successfully developed a glomerular mesangium-targeted PEG-PLGA NPs,which is potential for the treatment of MsPGN.

关 键 词：GLOMERULONEPHRITIS Mesangium MESANGIAL cells PEG-PLGA nanoparticles DEXAMETHASONE ACETATE 

分 类 号：R[医药卫生]