Management of diabetes mellitus–associated atherosclerosis via simvastatin-loaded novasomes

The impact of atherosclerosis on global healthcare systems is increasing rapidly. Understanding the complications arising from constricted and blocked arteries is essential for comprehending the full impact of atherosclerosis. Additionally, atherosclerosis is exacerbated by diabetes mellitus (DM). Simvastatin (SVS), an HMG-CoA reductase antagonist, is known to protect against DM-associated atherosclerosis due to its cardioprotective, antioxidant, and anti-inflammatory effects. However, SVS has limited efficacy due to its poor solubility, short half-life, hepatic metabolism, and low bioavailability. This study aimed to develop, evaluate, and enhance nasal SVS-loaded novasomes (SLNs) with a focus on efficacy, bioavailability, and solubility for the treatment of DM-associated atherosclerosis. The efficacy of an optimized SLN formulation was investigated in albino Wistar rats. The optimized SLN formulation demonstrated an increase in bioavailability of 8.23 times, permeation of 4.52 times, and a release of 3.88-fold. The nasal SLN was found to be superior in terms of CK-MB, LDH, HDL, LDL, cholesterol, triglycerides, glutathione, superoxide dismutase, and catalase. The effectiveness and safety of the nasal SLN were validated using histopathological and toxicity studies. These results suggest that nasal SLN delivery could be a potential treatment strategy for DM-associated atherosclerosis.