Development of Selenized Phytosomes for Sustained Release of Berberine and Synergistic Hypoglycemic Effect

The phytomedicine Berberine (Ber) exhibits hypoglycemic activity but suffers from poor oral efficacy. Selenium offers synergistic antidiabetic potential yet has a narrow therapeutic window. This study aimed to develop selenium‑decorated berberine phytosomes (Se@Ber‑PTs, i.e., phytosomes coated with a functional selenium layer) to enhance the combined hypoglycemic effects.

Se@Ber‑PTs were prepared by covalent coupling under a heated, nitrogen‑purged atmosphere, followed by thin‑film hydration, and then in situ reduction of sodium selenite with glutathione. The engineered nano-systems were thoroughly characterized for particle size, ζ‑potential, morphology, FTIR, and in vitro release. Subsequently, hypoglycemic effects were evaluated in alloxan‑induced diabetic rats after oral administration.

Se@Ber-PTs exhibited uniform core-shell nanovesicles with an average size of 109 nm, a PDI of 0.07, a ζ-potential of -21.42 mV, a drug loading of 5.27 ± 0.44%, and an encapsulation efficiency of 85.36 ± 3.75%, confirming successful selenium layering. The formulation showed the most sustained drug release, achieving a 24-hour cumulative release of 26% in pH 6.8 PBS. In diabetic rats, it produced a more pronounced and prolonged reduction in blood glucose compared with raw berberine and non-selenized phytosomes.

The selenium layer acts as a physical barrier for sustained release and provides intrinsic hypoglycemic activity, synergizing with berberine. This dual mechanism addresses the short duration of action and enhances the oral hypoglycemic efficacy while harnessing the safety of nano‑selenium, supporting selenized phytosomes as a versatile oral platform for poorly absorbed phytomedicines.

Selenization of berberine phytosomes provides a physical barrier for sustained release and introduces intrinsic hypoglycemic activity, yielding a synergistic enhancement of oral antidiabetic efficacy. These findings suggest that Se@Ber‑PTs hold promise as an effective oral formulation for diabetes management.