Lupeol-loaded PLGA particles conserve anti-topoisomerase activity and decrease the cytotoxicity of lupeol

Lupeol (LP), a bioactive triterpene, has been extensively studied for its chemoprotective, anti-inflammatory, and anti-arthritic properties. To enhance its bioavailability, lupeol-loaded polylactic-co-glycolic acid (PLGA) nanoparticles, designated T_LP14, were developed using the emulsification-evaporation method. These nanoparticles exhibited an average size of 339.8 nm, a polydispersity index (PdI) of 0.240, and an encapsulation efficiency of 38 %. In topoisomerase II inhibition assays, T_LP14 retained activity comparable to that of lupeol free, indicating that encapsulation does not impair its biological function. In vitro cytotoxicity assays on BEAS-2 and HEPG2 cell lines demonstrated that concentrations above 1250 μg/mL of T_LP14 induced minimal cytotoxic effects, suggesting low toxicity in non-tumor cells. Furthermore, ex vivo studies on peripheral blood mononuclear cells showed that a 1000 μg/mL concentration of free lupeol induced 28.01 % apoptosis, while the encapsulated formulation significantly reduced this adverse effect. These findings support the potential of T_LP14 nanoparticles as an effective controlled-release system for lupeol, enhancing its safety profile while preserving its therapeutic activity.