Linagliptin loaded chitosan nanoparticles for the efficient therapy of renal fibrosis

Chronic kidney disease (CKD), whose prevalence is rising substantially, has become a major global health challenge. In this study, we developed linagliptin-loaded chitosan nanoparticles (HCS-LGP NPs) for the treatment of renal fibrosis. The synthesized nanoparticles exhibited a uniform particle size of 178.8 ± 4.4 nm and a zeta potential of −29.9 ± 2.5 mV, along with acid-responsive drug release properties. In vitro , the HCS-LGP NPs showed efficient cellular uptake in TGF-β1-induced HK-2 cells and significantly inhibited cell proliferation by downregulating the expression of TGF-β1 and Collagen I. In vivo studies demonstrated effective renal accumulation of HCS-LGP NPs in rats with renal fibrosis. Treatment with HCS-LGP NPs significantly reduced serum creatinine, blood urea nitrogen, and the protein levels of TGF-β1 and Collagen I. Notably, the administration of HCS-LGP NPs promoted marked recovery from renal injury and markedly reduced collagen fiber deposition in rats with renal fibrosis. Histopathological analysis confirmed excellent biocompatibility, with no observable damage to the heart, liver, spleen, or lungs. These findings indicate that HCS-LGP NPs hold great potential as a targeted therapy for renal fibrosis, offering enhanced efficacy and a favorable safety profile.