Natural Deep Eutectic Solvents (NADES) to Enhance Berberine Absorption: An In Vivo Pharmacokinetic Study

Natural Deep eutectic solvents (NADES) are mixtures of small natural compounds having a melting point significantly lower than that of either individual component. Such solvents have gained much attention from the scientific community in the green chemistry area being considered useful to replace common organic solvents or can be used as administration vehicle. In this work NADES were prepared using food grade compounds and were tested as solvents for the alkaloid Berberine. The pharmacokinetic of the berberine solubilised in the most promising NADES showing difference compared to water suspension administration. MATERIAL/METHODS: NADES were prepared using different combinations of choline chloride, amminoacid and sugar or organic acid (malic, citric etc) aminoacid and sugars. Solubility of berberine was tested and the most promising eutectic were selected. The pharmacokinetic of berberine dispersed in water (20 mg/mL) and in selected NADES (20 mg/mL) was studied in mice. Plasmatic levels of berberine were measured by LC-MS/MS method showing increased plasmatic peak for NADES treated animals and showing a longer period of berberine permanence in plasma. RESULTS: NADES containing proline and malic acid were able to dissolve berberine hydrochloride better than water (from 2 to 10 time more). The most promising mixtures were studied in vivo. Compared to water we observe increase in plasmatic concentration from 2 to 20 times with significant changes in pharmacokinetic profile. CONCLUSIONS: Natural Deep Eutectic Solvents may be considered as attractive solubilisation agents and may play also a role in the increase of absorption of poorly bioavailable natural products such as berberine. The present study present the first results in term of administration in vivo of berberine containing NADES.