Oral supplementation of solvent-free kynurenic acid/cyclodextrin nanosponges complexes increased its bioavailability

Many nutraceuticals present problems due to their poor water solubility or stability, which prevents the final bioactivity achievement. For that reason, the oral administration of KYNA complexed with HPβ-CD and βNS-CDI nanosponges was evaluated in mice. The solvent-free technology was used to prepare the complexes in a complete comparison between kneading in ball milling and classical inclusion complex preparation. The solvent-free ones showed higher strength and efficiency with ball milling, considerably reducing time. A 50 mg KYNA/kg/day dosage was orally administered in formulations showing a higher bioavailability when the nutraceutical was complexed with βNS-CDI compared to HPβ-CD and free KYNA, respectively. Several antioxidant statuses demonstrated a higher global antioxidant level perfectly related to bioavailability. Finally, the formulation of KYNA reduced the temporal oxidative stress damage in the kidney and liver, making βNS-CDI the best formulation. These results suggest an important future application of cyclodextrin-based nanosponges for the oral delivery of nutraceuticals and their stabilization.