Curcumin, the principal bioactive polyphenol derived from the rhizome of Curcuma longa, has attracted substantial oncological research interest owing to its pleiotropic anticancer mechanisms — encompassing inhibition of NF-κB signalling, downregulation of cyclin D1, induction of caspase-3/9-mediated intrinsic apoptosis, and suppression of tumour angiogenesis through VEGF pathway modulation — demonstrated across a wide spectrum of cancer cell lines including MCF-7 breast adenocarcinoma, HeLa cervical carcinoma, and HCT116 colorectal carcinoma in preclinical models. However, the clinical translation of curcumin as an anticancer therapeutic has been severely constrained by its intrinsic physicochemical limitations: aqueous solubility below 11 ng/mL at physiological pH, rapid systemic metabolism to inactive glucuronide and sulfate conjugates with plasma half-life under 30 minutes following oral administration, and poor intestinal permeability attributable to P-glycoprotein-mediated efflux — collectively producing oral bioavailability below 1% in human pharmacokinetic studies. Polymeric nanoparticle encapsulation using biodegradable poly(lactic-co-glycolic acid) (PLGA) and its polyethylene glycol-conjugated derivative (PLGA-PEG) offers a validated strategy for overcoming these limitations through sustained release, enhanced cellular internalisation via endocytosis, and prolonged systemic circulation enabled by the PEG corona's steric barrier against opsonisation. This study reports the preparation of curcumin-loaded PLGA and PLGA-PEG nanoparticles by the nanoprecipitation method, their comprehensive physicochemical characterisation (DLS particle size, zeta potential, encapsulation efficiency, drug loading, FTIR, DSC), pH-responsive in vitro drug release kinetics at pH 7.4 (physiological) and pH 5.0 (tumour microenvironment), and in vitro anticancer efficacy against MCF-7 cells assessed by MTT assay, flow cytometric apoptosis analysis (Annexin V-FITC/PI), and cell cycle arrest profiling. PLGA-PEG nanoparticles (164±22 nm, PDI 0.14, zeta potential −14.2 mV, encapsulation efficiency 82.6%) achieved IC₅₀ of 41.2 µg/mL against MCF-7 cells at 48h — a 2.6-fold improvement over free curcumin IC₅₀ of 108.4 µg/mL — with pH-responsive accelerated release at tumour-mimicking pH 5.0 (94.1% cumulative release at 72h versus 81.4% at pH 7.4) and 63.0% total apoptotic population (early + late apoptosis) versus 19.4% for untreated control. These results confirm that PLGA-PEG nanoencapsulation substantially enhances curcumin's in vitro anticancer potency and support further in vivo evaluation in murine breast tumour models.
Rajiv Mehta Dhruvika Patel (Wed,) studied this question.