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 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.
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The authors declare no competing interests.
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The work was supported by the National Natural Science Foundation of China (Nos. 81473169 and 81130060).
LZ and SL designed the research; SL, Y-cZ, KP, and CL performed the research; LZ and Z-rZ contributed new reagents or analytic tools; SL analyzed the data and wrote the draft manuscript; LZ contributed to manuscript writing and proofreading.
About this article
PEGylated polylactide (PLA) and poly (lactic-co-glycolic acid) (PLGA) copolymers for the design of drug delivery systems
Journal of Pharmaceutical Investigation (2019)