Polymeric Nanoparticle-Based Drug Delivery Systems for Enhanced Anticancer Efficacy: Synthesis, Characterisation, and In Vitro Evaluation of PLGA and Chitosan Nanocarriers Loaded with Curcumin

Curcumin, the principal bioactive polyphenol of Curcuma longa, exhibits potent anticancer activity through simultaneous modulation of multiple oncogenic signalling pathways including NF-κB, Nrf2, mTOR, and Wnt/β-catenin. However, curcumin's clinical translation is severely impaired by its extremely poor aqueous solubility (11 ng/mL at pH 7.0), rapid metabolic inactivation, and low oral bioavailability (< 1%). Polymeric nanoparticle encapsulation represents a promising strategy to overcome these biopharmaceutical limitations by protecting curcumin from premature degradation, enabling sustained release at the tumour site via enhanced permeability and retention (EPR) effect, and facilitating cellular uptake through endocytic pathways. This study systematically synthesises and characterises curcumin-loaded nanoparticles using two distinct polymer matrices — poly(lactic-co-glycolic acid) (PLGA) via nanoprecipitation and chitosan via ionic gelation — and comprehensively evaluates their physicochemical properties, drug release kinetics, and anticancer efficacy against MCF-7 (breast cancer) and A549 (lung cancer) cell lines. PLGA-curcumin nanoparticles (PLGA-Cur-NP) exhibited particle size of 182±14 nm, zeta potential of −28.4±2.1 mV, and encapsulation efficiency of 88.3%, with sustained biphasic release of 91.2% drug over 72 hours. Chitosan-curcumin nanoparticles (CS-Cur-NP) showed particle size of 216±18 nm, zeta potential of +16.8±1.4 mV, and encapsulation efficiency of 82.7%, exhibiting pH-responsive drug release with accelerated release at pH 5.5 (tumour microenvironment). MTT assay demonstrated that PLGA-Cur-NP achieved IC₅₀ of 12.4 µg/mL against MCF-7, representing a 4.8-fold improvement over free curcumin (IC₅₀ = 59.7 µg/mL).