Formulation, Characterisation, and In-Vitro Evaluation of Chitosan-PEG Conjugated PLGA Nanoparticles for Targeted Curcumin Delivery in Breast Cancer Therapy

Curcumin (diferuloylmethane), a hydrophobic polyphenol derived from the rhizome of Curcuma longa, exhibits well-documented anti-tumour, anti-inflammatory, and antioxidant bioactivities across multiple cancer cell lines, including MCF-7 human breast adenocarcinoma. However, its therapeutic translation is severely impeded by poor aqueous solubility (< 1 µg/mL at physiological pH), rapid metabolic degradation, and systemic bioavailability below 1% following oral administration — collectively limiting its achievable tumour-site concentration to sub-therapeutic levels. Nanoparticulate encapsulation within biodegradable polymer matrices offers a rational strategy to overcome these limitations by protecting the hydrophobic payload from premature degradation, improving colloidal dispersion, and enabling surface functionalisation for receptor-mediated tumour targeting. This study reports the formulation, physicochemical characterisation, and in-vitro evaluation of six PLGA-based nanoparticle (NP) formulations incorporating curcumin at varying chitosan (CS) coating levels (5%, 10%, 15% w/w) and polyethylene glycol (PEG) conjugation, with a ternary formulation (F6) combining 10%CS and PEG surface modification. Nanoparticles were prepared by nanoprecipitation method with characterisation encompassing drug encapsulation efficiency (EE%), dynamic light scattering (DLS) particle size and zeta potential, polydispersity index (PDI), in-vitro drug release at pH 7.4 and pH 5.0 (simulating tumour microenvironment), FTIR spectroscopy, differential scanning calorimetry (DSC), transmission electron microscopy (TEM) structural analysis, MTT cell viability assay against MCF-7 cells, and colloidal stability study over 90 days. The ternary F6 formulation achieved the highest encapsulation efficiency (84.1%), smallest mean particle size (168 nm), most negative zeta potential (-34.8 mV), and lowest IC50 against MCF-7 cells (62.6 µg/mL versus 88.4 µg/mL for plain PLGA NPs and 42.8 µg/mL for free curcumin at 24h). In-vitro release studies confirmed sustained release over 24 hours with pH-responsive enhanced release at pH 5.0, simulating tumour microenvironment conditions. Haemolysis assay confirmed biocompatibility at therapeutic concentrations (haemolysis below 5% at 1 mg/mL). The F6 ternary formulation is recommended as an optimised platform for further in-vivo evaluation in breast cancer xenograft models.