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^®). 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 × 10^-5 ± 7.89 × 10^-6 cm/s), were observed when compared to standard/unformulated berberine (4.93 × 10^-6 ± 4.28 × 10^-7 cm/s). Demonstrating better uptake, LMB achieved significant increases in AUC_0-24 and C_max compared to the standard formulation (AUC: 78.2 ± 14.4 ng h/mL vs. 13.4 ± 1.97 ng h/mL, respectively; <i>p</i> < 0.05; C_max: 15.8 ± 2.6 ng/mL vs. 1.67 ± 0.41 ng/mL) in a pilot study of healthy volunteers (<i>n</i> = 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.