Fabrication of losartan-loaded chitosan-cloaked dopamine nanoparticles for improving diabetic nephropathy via regulation of oxidative stress and blood glucose

Abstract

Diabetic nephropathy (DN) is a significant problem for people with diabetes, and its progression is strongly associated with oxidative stress induced by high blood sugar levels (hyperglycemia). This study presents a novel type of losartan-loaded chitosan-cloaked dopamine nanoparticles (CSDLNPs). It can specifically aggregate in damaged kidneys, lower blood glucose levels, and ameliorate the damage caused by oxidative stress. CSDLNPs exhibit excellent dispersion physiological stability and sensitive release under an acidic pH milieu. Additionally, they have potent scavenging capabilities against a wide range of reactive nitrogen and oxygen radicals. Furthermore, in vitro, investigations validate that CSDLNPs exhibit superior biocompatibility, facilitate specific absorption in the HK-2 proximal tubule epithelial cell line, and effectively mitigate oxidative stress generated by high hyperglycemia. Following CSDLNPs treatment, DN exhibits a reduction in fasting blood glucose (FBG) levels and a restoration of urine and blood indices to levels close to normal. The H&E pathological staining results demonstrate that CSDLNPs effectively suppress collagen deposition, glycogen accumulation, and renal interstitium enlargement, indicating remarkable therapeutic efficacy. Furthermore, dopamine is a drug carrier and antioxidant without needing an external carrier, demonstrating superior biosafety and potential for translation to diabetic nephropathy.