Chitooligosaccharide-modified PLGA-loaded PPD nanoparticles ameliorated sepsis-associated acute kidney injury via the NF-κB signaling pathway.

Abstract

Objectives: Sepsis-associated acute kidney injury (SA-AKI) is a significant clinical challenge with high morbidity and mortality. Low bioavailability of protopanaxadiol (PPD) limits its clinical application. In this study, PPD was encapsulated with chitooligosaccharide (COS) modified polylactic-co-glycolic acid (PLGA) to develop novel nanomedicines for the treatment of SA-AKI.

Methods: COS-PLGA-PPD nanoparticles were prepared by emulsified solvent evaporation method, and their properties were evaluated. In vitro, the anti-inflammatory and protective effects of COS-PLGA-PPD NPs were investigated in a cellular model of LPS-induced NRK-52E cells and their uptake in Caco-2 cells. Indicators of renal injury, inflammation, and NF-κB signaling pathway were evaluated by injecting LPS into SD rats and inducing SA-AKI model in vivo. The oral bioavailability of nanoparticles was evaluated by pharmacokinetics.

Results: Compared with PPD and unmodified nanoparticles, COS-PLGA-PPD NPs were more stable, with a particle size of 139.69 nm, which enhanced the viability of NRK-52E cells, increased the uptake of Caco-2 cells, alleviated the symptoms of SA-AKI in rats, inhibited the NF-κB signaling pathway, reduced the expression of inflammatory factors, and had a bioavailability 1.7-fold that of PPD.

Conclusion: COS-PLGA-PPD NPs ameliorate LPS-induced SA-AKI in rats by inhibiting the NF-κB signaling pathway, providing a basis for the treatment of SA-AKI.