Improving Oral bioavailability: Lipid-polymeric nanoparticles of simvastatin and coenzyme Q10

This study focuses on the development of lipid–polymeric nanoparticles (LPNs) to enhance the apparent solubility and oral bioavailability of simvastatin (SIM) and coenzyme Q10 (CoQ10) through the creation of a supersaturation state. SIM is a widely prescribed HMG-CoA reductase inhibitor used in the treatment of hypercholesterolemia and the prevention of cardiovascular diseases, while CoQ10 is a lipophilic compound essential for mitochondrial energy (ATP) production and antioxidant defense. Combined therapy with CoQ10 and statins is recommended because prolonged statin use decreases endogenous CoQ10 levels, which may result in muscle fatigue, myalgia, and mitochondrial dysfunction. Therefore, improving the oral bioavailability of both compounds can promote better absorption and therapeutic efficacy, while CoQ10 supplementation helps mitigate statin-related adverse effects and maintain muscle and cardiac function. LPNs were produced using a selfassembly method and showed optimal performance at 1 mg⋅mL􀀀 1, with high encapsulation efficiency (81.93 ± 3.16% for LPN-SIM and 81.20 ± 3.65% for LPN-CoQ10) and stable physicochemical properties. They exhibited a uniform size distribution (polydispersity index 0.155–0.209) and positive surface charge (zeta potential +31.33 to +33.23 mV). Transmission electron microscopy confirmed a spherical morphology, and stability was maintained at 5 ◦C for 28 days. Supersaturation studies demonstrated rapid dissolution for the formulations. LPN-SIM showed a significantly higher area under the curve (AUC) than the plain suspension, with up to a 10.6-fold solubility enhancement in FaSSGF and 2.1-fold in FaSSIF. In vivo studies in rats confirmed that LPNs were safe and well tolerated, showing no hepatic or renal impairment. These findings highlight the clinical potential of LPNs to optimize statin therapy and improve cardiovascular treatment outcomes.