Ricobendazole-loaded nanoformulations for improved anthelmintic toxicity

Abstract

Benzimidazole derivatives remain the first-line anthelmintics in veterinary medicine; however, their low aqueous solubility and poor pharmacokinetic profiles limit their therapeutic potential. Ricobendazole, the active metabolite of albendazole, exhibits improved solubility compared to its parent compound but is still constrained by formulation challenges. In this study, novel Ricobendazole-loaded Nanostructured Lipid Carriers were developed using a double emulsion method to improve drug delivery, colloidal stability, and biological efficacy. Among three initial formulations, one of them was selected based on its superior physicochemical characteristics, reproducibility, and suitability for parenteral administration. The selected formulation exhibited a hydrodynamic diameter below 110 nm, relatively low polydispersity, and negative zeta potential, with stable encapsulation efficiency (>45 %) and no significant drug leakage over 30 days. DSC and Laurdan fluorescence analyses confirmed successful drug incorporation and lipid matrix reorganization, indicating increased matrix crystallinity upon drug loading. TEM and SEM analyses revealed spherical morphology and confirmed particle size distribution. Viscosity studies demonstrated Newtonian behavior at 25 °C and 37 °C, while Turbiscan analysis indicated moderate sedimentation without irreversible destabilization, particularly at 25 °C. Functionally, the selected formulation demonstrated higher in vivo anthelmintic activity against C. elegans compared to the free drug, achieving significant reduction in worm motility at lower concentrations and suggesting enhanced drug bioavailability. Overall, this nanocarrier platform offers a promising approach for improving the apparent solubility, stability, and efficacy of ricobendazole, with potential applicability to other poorly soluble anthelmintics.