PLGA nanoparticles enhanced cardio-protection of scutellarin and paeoniflorin against isoproterenol-induced myocardial ischemia in rats

This study aims to examine the impact of the microfluidic preparation process on the quality of poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-delivered with scutellarin (SCU) and paeoniflorin (PAE) in comparison to a conventional emulsification method and to evaluatethe potential cardio-protective effect of SCU-PAE PLGA NPs produced through emulsification method. As compared with microfluidics, the nanoparticles prepared by emulsification method exhibited a smaller size, higher encapsulation efficiency, higher drug loading and lower viscosity for injection. Subsequently, a rat myocardial ischemia (MI) was established using male Sprague-Dawley (SD) rats (250 ± 20 g) subcutaneously injected with 85 mg/kg isoproterenol (ISO) for two consecutive days. The pharmacokinetic findings demonstrated that our SCU-PAE PLGA NPs exhibited prolonged blood circulation time in MI rats, leading to increased levels of SCU and PAE in the heart. This resulted in significant improvements in electrocardiogram and cardiac index, as well as reduced serum levels of CK, LDH, AST. Histopathological analysis using H&E and TUNEL staining provided further evidence of improved cardiac function and decreased apoptosis. Additionally, experiments measuring SOD, MDA, GSH, NO, TNF-α and IL-6 levels indicated that SCU-PAE PLGA NPs may effectively treat MI through oxidative stress and inflammatory pathways, thereby establishing it as a promising therapeutic intervention.