Mixed Micelles with Galactose Ligands for the Oral Delivery of Berberine to Enhance Its Bioavailability and Hypoglycemic Effects.

Abstract

Diabetes mellitus (DM) has become an epidemic disorder that is an escalating public health risk. Currently, DM treatment is highly challenging due to temporary medical relief rather than a permanent cure. This article reports a ligand-anchored mixed micellar system formed by phospholipids and N -oleoyl-D-galactosamine aiming to enhance the oral bioavailability and hypoglycemic effects of berberine, an antidiabetic agent with poor absorption. Berberine-loaded mixed micelles (BBMMs) were prepared through a solvent diffusion technique. The resulting BB-MMs were characterized by particle size, potential, morphology, entrapment efficiency (EE) and in vitro release. The oral pharmacokinetics and hypoglycemic efficacy of BB-MMs were evaluated in rats and compared with a berberine suspension. As a result, BB-MMs prepared with the preferable formulation had a particle size of approximately 100 nm with an EE of over 85%. BB-MMs exhibited sustained drug release owing to the entrapment in the micelles. After oral administration, BB-MMs ameliorated the pharmacokinetic profile of berberine and significantly enhanced its oral bioavailability (317.17% relative to the suspension). The pharmacological effect (PE) of BB-MMs was approximately 3.44 times greater than that of the suspension. In addition, in situ single-pass intestinal perfusion and cellular testing results illustrated that BB-MMs had good intestinal permeability and cellular uptake. Our findings demonstrate that the oral bioavailability and hypoglycemic effects of berberine could be largely enhanced by encapsulation into mixed micelles with a galactose moiety. Thus, galactosylated micelles may be promising for developing berberine nanomedicines to fight DM.