Polymeric PLGA Nanoparticles Loaded with Acalypha monostachya Leaf Hexane Extract: A Novel Strategy for Antineoplastic Activity

<b>Background/Objectives</b>: <i>Acalypha monostachya</i> is used in rural communities in Mexico as a traditional remedy for cancer, and we previously observed cytotoxic activity of its extracts against MDA-MB-231 and HeLa cells. <b>Methods</b>: Because lipophilic plant fractions disperse poorly in water, we encapsulated the hexane leaf extract (LHE) of <i>A. monostachya</i> in poly (lactic-co-glycolic acid) (PLGA) nanoparticles prepared by nanoprecipitation, characterized them physicochemically, and evaluated their in vitro cytotoxicity. <b>Results</b>: The selected extract/polymer ratio (5/50, <i>w</i>/<i>w</i>) produced nanoparticles with a mean diameter of 131.4 ± 0.5 nm and a PDI of 0.122 ± 0.028, with an encapsulation efficiency of 92.03% and a loading of 8.43%. We next evaluated cytotoxicity by MTT after 24 h in HeLa and MDA-MB-231 cells and compared the response with non-tumorigenic HaCaT keratinocytes. Encapsulation increased potency relative to free LHE, yielding IC₅₀ values of 30 µg/mL (HeLa), 60 µg/mL (MDA-MB-231), and 95 µg/mL (HaCaT). These values corresponded to selectivity indices of 3.2 (HaCaT/HeLa) and 1.6 (HaCaT/MDA-MB-231). <b>Conclusions</b>: Overall, encapsulation of LHE in PLGA nanoparticles yields an aqueous PLGA nanoparticle suspension and is associated with improved in vitro potency while maintaining measurable selectivity against cancer cells.