Preparation of protamine-hyaluronic acid coated core-shell nanoparticles for enhanced solubility, permeability, and oral bioavailability of decoquinate

Decoquinate (DQ) has low oral bioavailability owing to its poor water solubility. In this study, a DQ solid dispersion (DQ-SD) was fabricated using mechanochemical technology to encapsulate DQ and improve its oral bioavailability. DQ-SD is easily generated via self-assembly in the aqueous phase to form micelles consisting of disodium glycyrrhizinate (Na2GA) nanoparticles with a protamine (PRM) and anionic hyaluronic acid (HA) layers. The spherical DQ nanoparticles with an average diameter of 114.95 nm were obtained in an aqueous phase with a critical micelle concentration of 0.157 mg/mL, zeta potential of -38.38 mV, polydispersity index of 0.200, and drug loading of 5.66 %. The dissolution rate and cumulative release of DQ-SD were higher than those of pure DQ. Furthermore, the bioavailability of DQ-SD was approximately 6.3 times higher than that of pure DQ. Pharmacokinetic and biodistribution studies indicated that DQ-SD possessed a significantly higher concentration in the blood and preferential liver tissue accumulation, than that of pure DQ. The developed DQ-SD exhibited considerable potential for developing old DQ for a new application as a hematogenous parasite drug and provides a reference for developing more efficient delivery systems for hydrophobic bioactive agents.

Automated summary

In this study, a solid dispersion of Decoquinate (DQ-SD) was fabricated using mechanochemical technology to improve its oral bioavailability. The results showed that DQ-SD had a higher dissolution rate, cumulative release, and bioavailability compared to pure DQ. Pharmacokinetic and biodistribution studies also demonstrated that DQ-SD had a higher concentration in the blood and preferential liver tissue accumulation. This research provides a reference for developing hematogenous parasite drugs and more efficient delivery systems for hydrophobic bioactive agents.