PLGA-PEG Nanoparticles Co-encapsulating Curcumin and Docetaxel for Targeted Breast Cancer Therapy

Breast cancer remains the most commonly diagnosed malignancy in women worldwide, accounting for approximately 2.3 million new cases and 685,000 deaths annually. Docetaxel, a potent taxane chemotherapy agent, is severely limited by dose-limiting toxicity and low tumour selectivity. Curcumin exerts complementary anti-cancer activity through NF-kB and STAT3 pathway inhibition but is essentially non-bioavailable orally due to rapid hepatic metabolism. This study synthesises and optimises folate-conjugated PLGA-PEG nanoparticles co-loaded with curcumin and docetaxel using Box-Behnken RSM. The optimised formulation (FO) exhibits particle size 187.4 +/- 9.3 nm, PDI 0.183, zeta potential -28.4 +/- 2.3 mV, curcumin EE 78.4%, and docetaxel EE 82.7%. Sustained biphasic release reaches 93.7% at 72h following Korsmeyer-Peppas anomalous diffusion kinetics. Folic acid functionalisation achieves 3.8-fold enhanced cellular uptake in MCF-7 cells. Cytotoxicity IC50 values of 0.38 ug/mL (MCF-7) and 0.47 ug/mL (MDA-MB-231) are 5.6-fold superior to free drug combination, with combination index (CI) 0.31-0.42 confirming strong synergism.This work establishes folate-targeted PLGA-PEG co-delivery as a scientifically robust nanomedicine strategy for improving the therapeutic index of curcumin-docetaxel combination therapy in breast cancer