Evaluating the Biological Activities of Oleanolic Acid and Apigenin in a 2-in-1 Nanoparticulate System: A Proof-of-concept Study.

BACKGROUND

Apigenin (APG) and Oleanolic Acid (OA) exhibit diverse biological activities; however, their pharmaceutical applications are limited by poor solubility, low bioavailability, and restricted permeability. This study developed a hybrid nanoparticulate system consisting of apigenin nanoparticles loaded into oleanolic acid micelles, named 2-in-1-NPs, to enhance their therapeutic potential. It was designed as a pilot study to identify the most promising biological activity of the 2-in-1-NPs.

METHODS

APG nanoparticles were prepared using the liquid anti-solvent method, while OA micelles were formulated via thin-film hydration. The hybrid system was characterized in terms of particle size, zeta potential, polydispersity index, encapsulation efficiency, and an in vitro drug release study.

RESULTS

The optimized hybrid 2-in-1 nanoparticle formulation exhibited a mean particle size of 150.4 ± 0.055 nm with sustained drug release over 72 hours, and high encapsulation efficiencies of 83 ± 0.577% for OA-MM and 92 ± 0.431% for APG-NP. While APG and OA alone showed limited antimicrobial activity against Escherichia coli, Salmonella typhi, Staphylococcus aureus, and Bacillus cereus, the hybrid nanoparticle system significantly enhanced anti-inflammatory activity, demonstrated by a marked reduction in IL-6 levels (p < 0.0001) compared with free or individually loaded drugs, and showed increased cytotoxicity against HepG-2 liver cancer cells with an IC₅₀ of 16.988 μg/mL, highlighting its potential for improved therapeutic efficacy.

DISCUSSION: The results demonstrate that the developed system successfully transports the drugs through the cell membrane and exhibits synergistic or additive biological activities, including antiinflammatory and anticancer effects.

CONCLUSION

The hybrid 2-in-1-NPs system presents a promising platform for the treatment of various diseases, offering enhanced bioactivity and therapeutic efficacy.