Oleyl-hyaluronate nanoparticles for enhanced peroral bioavailability of encapsulated Coenzyme Q10

Hyaluronic acid (HA) is a biocompatible, mucosal-interacting polysaccharide that offers unique advantages for oral drug delivery. Chemical modification with hydrophobic groups transforms HA into an amphiphilic polymer capable of self-assembly and encapsulation of poorly soluble compounds. In this work, we developed an oral delivery system based on oleyl-hyaluronate (O-HA) for coenzyme Q10 (CoQ10), a lipophilic antioxidant with limited solubility and low bioavailability. The coenzyme Q10-loaded oleyl-hyaluronate nanoparticles (O-HAQ10) were prepared using a multistep solvent evaporation method, achieving a high CoQ10 loading of up to 13.8 g/L and an encapsulation efficiency typically exceeding 90%. Crucially, this platform achieved an exceptionally high drug loading capacity, substantially minimizing the surfactant burden typically required to stabilize highly lipophilic payloads. The nanoparticles exhibited nanoscale dimensions (200-300 nm), as confirmed by dynamic light scattering (DLS) and scanning electron microscopy (SEM). Comprehensive in vitro evaluation confirmed robust cytocompatibility with the Caco-2 human intestinal epithelial cell line. Furthermore, studies on porcine intestine demonstrated significantly enhanced mucosal accumulation compared to commercial liposomal and oil-based formulations, even following simulated gastric exposure. In vivo pharmacokinetic evaluation in mice confirmed a 72% increase in systemic bioavailability relative to the clinical gold-standard oil-based control. These findings highlight the potential of hydrophobically modified HA as a highly efficient, versatile platform for the peroral delivery of poorly soluble bioactives.