Nanoformulated resveratrol enhanced the treatment of atherosclerosis

Atherosclerosis, a leading pathological basis of cardiovascular diseases, is closely associated with oxidative stress, inflammation, and lipid metabolism disorders. Resveratrol has demonstrated anti-atherosclerotic activity, but its clinical application is limited due to poor solubility, short circulation time, and lacking targeting. To overcome these limitations and establish a multi-pathway synergistic strategy for treating atherosclerosis, we designed a stealth lipid nanosphere system with macrophage-targeted and pH-responsive properties. The complete lipid nanospheres were evaluated for biocompatibility, cellular uptake, antioxidant and anti-inflammatory activities, as well as the inhibitory effects on foam cell formation. Pharmacokinetics and targeting efficiency were analyzed using both high-performance liquid chromatography and an in vivo imaging system. Therapeutic efficacy and biosafety were assessed via serum biochemistry and histopathological examination. Results showed that the complete lipid nanospheres exhibited uniform spherical morphology, high encapsulation efficiency, and pH-responsive release. In vitro evaluations demonstrated excellent biocompatibility of the complete lipid nanospheres, along with selective uptake by activated macrophages. Furthermore, the complete lipid nanospheres exhibited potent antioxidant and anti-inflammatory effects, as well as significant inhibition of foam cell formation. In vivo studies demonstrated that the treatment significantly extended the plasma half-life of resveratrol while enhancing its targeted accumulation within atherosclerotic plaques. In ApoE −/− mice with atherosclerosis, this intervention exhibited multifaceted therapeutic effects, including attenuation of oxidative stress, suppression of inflammatory responses, and reduction of lipid deposition. The study concludes that the complete formulation, stealth folic acid-modified pH-responsive lipid nanospheres, can specifically target resveratrol to the activated macrophages in plaques and inhibit plaque progression with minimal side effects, primarily due to resveratrol's antioxidant, anti-inflammatory, and lipid metabolism regulatory activities.