Calcium Carbonate-Stabilized Nano-Caffeine Emulsion Attenuates Diabetic Cardiomyopathy via Antioxidant,...

Type 2 diabetes mellitus (T2DM) is one of the most commonly diagnosed metabolic diseases. Notably, two-thirds of diabetic patients may develop diabetic cardiomyopathy (DCM), a life-threatening condition for which no curative treatment currently exists.

This study aimed to investigate the potential ameliorative effects of caffeine against DCM development, utilizing a novel oral sustained-release caffeine-loaded Pickering emulsion formula stabilized by calcium carbonate nanoparticles to enhance its pharmaceutical and pharmacological properties. Eighty-four rats were divided into seven groups: control, caffeine, nano-caffeine, diabetic, diabetic + rosuvastatin, diabetic + caffeine, and diabetic + nano-caffeine.

Our findings demonstrated that the newly developed nano-caffeine formulation significantly downregulated myocardial injury markers (CK-MB, cTnI, ALT, AST, and LDH) and markedly ameliorated myocardial tissue injury and fibrosis, as confirmed by histopathological examination and desmin/α-SMA expression analysis. Additionally, the nano-caffeine treatment reduced inflammatory cytokines (TNF-α and IL-1β), attenuated hyperlipidemia, decreased iNOS and NO myocardial concentrations, and upregulated protective antioxidants (Nrf2, GSH, GSH-Px, SOD, and catalase) compared to the control group. Importantly, the cardioprotective effects of nano-caffeine were more pronounced than those observed in caffeine-treated diabetic rats. Furthermore, a novel, simple, and validated HPLC method was employed to quantify caffeine levels in cardiac tissues in all groups. The analysis revealed significantly higher caffeine concentrations in the nano-caffeine group compared to other groups, indicating improved tissue delivery.

The formulation significantly enhances the cardioprotective effects of caffeine against myocardial injury in T2DM rats by optimizing its pharmacodynamic and pharmacokinetic properties.