Dual‐Phytocompound‐Loaded Polycaprolactone Nanoparticles: Formulation, Characterization, In Vitro Antioxidant and Antitumor Evaluation

Abstract

ABSTRACT Betulinic acid (BA) and taraxerol (TA) have gained attention for their potent pharmacological antioxidant and antitumor properties. However, their poor water solubility limits clinical use. In this study, polycaprolactone (PCL) nanocarriers were prepared via a single emulsion–solvent evaporation method to co‐encapsulate BA and TA, thereby improving their solubility, stability, and bioavailability. The resulting particles had an average size of 261 ± 7.70 nm and a zeta potential of −18.00 ± 0.21 mV. Encapsulation efficiency was 82.77% for BA and 69.84% for TA, with drug loadings of 6.57 ± 0.45% and 5.54 ± 0.23%, respectively. XRD study confirmed the formulation's amorphous state, which favors drug dissolution, and TEM showed a spherical shape. In vitro release tests revealed a biphasic pattern: an initial burst followed by sustained release. The co‐encapsulated nanocarriers exhibited enhanced antioxidant activity compared to free and individually encapsulated compounds, as shown by improved free radical scavenging. Additionally, the nanoformulation demonstrated significant antiproliferative effects against HepG2 and HeLa cell lines, indicating strong antitumor potential. These results suggest that PCL nanocarriers co‐loaded with BA and TA provide a versatile and effective platform to enhance the therapeutic effects of natural triterpenoids, with promising applications for managing oxidative stress–related conditions and cancer.