Carvedilol-loaded self-nanoemulsifying drug delivery system target diabetic nephropathy: preclinical evidence of antioxidant and antifibrotic effects

Diabetic nephropathy (DN) is a significant complication of diabetes, leading to chronic kidney failure and end-stage renal disease. While traditional treatments exist, innovative strategies are being investigated to enhance DN management. This study examines a novel nanosized formulation of carvedilol (CVL), a drug recognized for its β-blocker and α-1-adrenoreceptor antagonist properties. We developed a self-nanoemulsifying drug delivery system (SNEDS) to assess its potential in improving DN outcomes. DN was induced in rats using streptozotocin (STZ), and the animals received oral administration of either CVL or CVL-SNEDS for 6 weeks. We measured body weight, blood glucose levels, creatinine, blood urea nitrogen (BUN), albumin-creatinine ratio (ACR), kidney injury molecule-1 (KIM-1), oxidative stress, and inflammation. Kidney tissues were also examined for damage and fibrosis markers, particularly transforming growth factor beta-1 (TGF-β1). Diabetic rats exhibited weight loss, hyperglycemia, elevated creatinine, BUN, ACR, KIM-1, increased oxidative stress, and inflammation, along with notable renal damage and higher TGF-β1 expression. Treatment with CVL-SNEDS significantly improved these parameters, reducing blood glucose levels by 51%, creatinine by 39%, BUN by 67%, and ACR by 78%, while also alleviating inflammation and oxidative stress and protecting against kidney damage and fibrosis. These findings suggest that CVL-SNEDS may represent a promising therapeutic approach for slowing DN progression by enhancing glycemic control and mitigating fibrosis, inflammation, and oxidative stress.