TY - JOUR AU - Li Sha AU - Zeng Ying-chun AU - Peng Ke AU - Liu Chang AU - Zhang Zhi-rong AU - Zhang Ling PY - 2018 TI - Design and evaluation of glomerulus mesangium-targeted PEG-PLGA nanoparticles loaded with dexamethasone acetate JF - Acta Pharmacologica Sinica; Vol 40, No 1 (January 2019): Acta Pharmacologica Sinica Y2 - 2018 KW - N2 - 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-speciļ¬c 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 kidney cortex 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. UR - http://www.chinaphar.com/article/view/9909