Simvastatin-Loaded Nanoniosome Protects H9c2 Cells from Oxygen-Glucose Deprivation/Reperfusion Injury by Downregulating Inflammation

Background: Simvastatin (SIM) has anti-inflammatory and antioxidant properties against cardiac ischemia/reperfusion injury (I/RI). However, it suffers from low bioavailability and a short half-life. Nanoniosomes are novel drug delivery systems that may increase SIM effectiveness. The present research evaluates the impact of SIM-loaded nanoniosomes on the oxygen-glucose deprivation/reperfusion (OGD/R) injury model of H9c2 cells. Methods: Cells were seeded based on five groups: (1) control; (2) OGD/R; (3) OGD/R receiving SIM; (4) OGD/R receiving nanoniosomes; and (5) OGD/R receiving SIM‑loaded nanoniosomes. OGD/R injury of the H9c2 cells was treated with SIM or SIM‑loaded nanoniosomes. Cell viability, two inflammatory factors, necroptosis factors, along with HMGB1 and Nrf2 gene expressions were assessed. Results: The cells treated with SIM‑loaded nanoniosomes showed a significant elevation in the cell viability and a reduction in HMGB1, Nrf2, TNF-α, IL-1β, RIPK1, and ROCK1 expression levels compared to the OGD/R and SIM groups. Conclusion: Based on our findings, nanoniosomes could safely serve as a drug delivery system to counterbalance the disadvantages of SIM, resulting in improved aqueous solubility and stability.