Cardioprotective Effect of Nanoencapsulated α-Amyrin in Spontaneously Hypertensive Rats with Metabolic Syndrome

Background/Objectives: Metabolic syndrome (MS) encompasses a cluster of disorders that significantly increase cardiovascular risk. While α-amyrin exhibits antioxidant and anti-inflammatory properties, its poor aqueous solubility and low oral bioavailability hinder its clinical use. This study evaluated the cardioprotective effects of α-amyrin-loaded polymeric nanocapsules (NCαA) in spontaneously hypertensive rats (SHR) with sucrose-induced MS. Methods: First, NCαA was prepared via interfacial deposition of a preformed polymer following organic solvent displacement. The formulation was characterized for particle size, zeta potential, morphology, encapsulation efficiency, and storage stability. Spontaneously hypertensive rats (SHR) received 20% sucrose for 8 weeks and were treated daily by oral gavage for 28 days with NCαA (0.1, 0.3, or 1 mg/kg), unformulated α-amyrin (1 mg/kg), hydrochlorothiazide (25 mg/kg), vehicle, or blank nanocapsules. Cardiovascular, electrocardiographic, echocardiographic, vascular, renal, and biochemical parameters were subsequently assessed. Results: Polymeric NCαA showed spherical and uniform morphology (195.10 ± 1.55 nm; PDI: 0.144; zeta potential: −52.60 mV), 85.85% encapsulation efficiency, efficient sustained release, and 90-day shelf-life stability. In vivo, MS control rats exhibited significant weight gain, hypertension, increased S-wave negative deflection depth, reduced ejection fraction, impaired acetylcholine-mediated vasodilation, depressed serum nitrite, and elevated malondialdehyde. Treatment with NCαA (particularly at 0.3 and 1 mg/kg), unlike unformulated α-amyrin, prevented excessive weight gain, normalized blood pressure, reversed electrophysiological/echocardiographic markers of cardiac overload, restored nitric oxide bioavailability, attenuated lipid peroxidation, and maintained renal hydroelectrolytic balance. Conclusions: Polymeric nanoencapsulation yielded stable nanocapsules with high sustained release, overcoming the biopharmaceutical limitations of α-amyrin. NCαA provides comprehensive cardioprotection against MS-induced damage, representing a promising multi-target strategy for cardiometabolic disorders.