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

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.

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.

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.

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.

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