Characterization and Pharmacokinetic Assessment of a New Berberine Formulation with Enhanced Absorption In Vitro and in Human Volunteers

Berberine is a plant-origin quaternary isoquinoline alkaloid with a vast array of biological activities, including antioxidant and blood -glucose-and blood-lipid-lowering effects. However, its therapeutic potential is largely limited by its poor oral bioavailability. The aim of this study was to investigate the in vitro solubility and Caco-2 cell permeability followed by pharmacokinetic profiling in healthy volunteers of a new food-grade berberine delivery system (i.e., Berberine LipoMicel (R)). X-ray diffractometry (XRD), in vitro solubility, and Caco-2 cell permeability indicated higher bioavailability of LipoMicel Berberine (LMB) compared to the standard formulation. Increased aqueous solubility (up to 1.4-fold), as well as improved Caco-2 cell permeability of LMB (7.18 x 10(-5) +/- 7.89 x 10(-6) cm/s), were observed when compared to standard/unformulated berberine (4.93 x 10(-6) +/- 4.28 x 10(-7) cm/s). Demonstrating better uptake, LMB achieved significant increases in AUC(0-24) and Cmax compared to the standard formulation (AUC: 78.2 +/- 14.4 ng h/mL vs. 13.4 +/- 1.97 ng h/mL, respectively; p < 0.05; C-max: 15.8 +/- 2.6 ng/mL vs. 1.67 +/- 0.41 ng/mL) in a pilot study of healthy volunteers (n = 10). No adverse reactions were reported during the study period. In conclusion, LMB presents a highly bioavailable formula with superior absorption (up to six-fold) compared to standard berberine formulation and may, therefore, have the potential to improve the therapeutic efficacy of berberine. The study has been registered on ClinicalTrials.gov with Identifier NCT05370261.

Automated summary

This study investigated the in vitro solubility and Caco-2 cell permeability of a new food-grade berberine delivery system, as well as its pharmacokinetic profiling in healthy volunteers. The results showed that the new delivery system exhibited higher bioavailability and absorption compared to the standard formulation, potentially improving the therapeutic efficacy of berberine.