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Abstract

Curcumin, a natural polyphenolic compound derived from Curcuma longa, has long been recognized for its potent anticancer, anti-inflammatory, and antioxidant activities. Despite its therapeutic promise, the clinical translation of curcumin has been hindered by its low aqueous solubility, poor bioavailability, and rapid systemic elimination. To address these limitations, this study reports the development of curcumin-loaded poly(lactic-co-glycolic acid) nanoparticles (Cur-PLGA NPs) prepared via the nanoprecipitation method. The nanoparticles were thoroughly characterized for their structural, morphological, and functional properties. Transmission electron microscopy revealed a uniform spherical morphology with nanoscale dimensions averaging ~120 nm, while drug encapsulation efficiency exceeded 80%, highlighting the suitability of PLGA as a delivery matrix. In vitro release studies demonstrated a sustained and controlled release profile extending over 72 h, thereby ensuring prolonged drug availability. Cellular uptake investigations using MCF-7 breast cancer cells confirmed efficient nanoparticle internalization, attributed to nanoscale size and surface properties. Cytotoxicity assessments revealed significantly enhanced anticancer efficacy of Cur-PLGA NPs compared to free curcumin, with a marked reduction in IC₅₀ values. Mechanistic analysis through apoptosis assays indicated that treatment with Cur-PLGA NPs upregulated pro-apoptotic markers including caspase-3 and Bax, confirming the activation of programmed cell death pathways. Collectively, these results establish that polymeric encapsulation of curcumin enhances its stability, bioavailability, and therapeutic performance. This study underscores the potential of Cur-PLGA nanoparticles as a promising nanocarrier system for breast cancer therapy and provides a foundation for future in vivo evaluations and clinical translation.