Stingless bee propolis-loaded alginate/zinc nanogels: Enhanced propolis bioavailability and effects on melanoma cells migration.

Bioactive compounds with low aqueous solubility often exhibit limited bioavailability, which restricts their therapeutic potential. This study explores the antimelanoma activity of the dichloromethane propolis extract (DPE), a terpene-rich fraction from the stingless bee Melipona quadrifasciata and enhances its solubility via encapsulation in zinc-crosslinked alginate nanogels (pNG) through ionic gelation technique. Unlike its well-studied polar counterpart, the non-polar and semi-polar fraction remains largely unexplored, offering new biological opportunities to treat diseases such as melanoma. The propolis-loaded nanogel properties were fully explored, as well as their nanostructural and stability features, using state-of-the-art techniques such as SEM, TEM, zeta potential, NMR & HPSEC. The nanogels displayed excellent colloidal stability and controlled release in phosphate (pH 7.4) and acetate (pH 5.5) buffers, with a faster propolis release observed under neutral pH. DPE significantly inhibited melanoma cell migration at 15 μg mL-1 without affecting fibroblasts, indicating selective pharmacological activity. Encapsulation further enhanced bioavailability, reducing the effective concentration to 0.62 μg mL-1 pNG. This study highlights the therapeutic potential of propolis terpene-rich fraction and introduces zinc-crosslinked nanogels as a promising drug-delivery platform with potential use in future in vivo and clinical tests to treat melanoma cases.