Formulation and In Vitro Characterisation of Chitosan-Alginate Nanoparticles Loaded with Curcumin for Targeted Colon Cancer Drug Delivery: Effect of Polymer Ratio on Encapsulation Efficiency, Release Kinetics, and Cytotoxicity

Curcumin (diferuloylmethane), the principal bioactive polyphenol of Curcuma longa, exhibits documented antiproliferative, anti-inflammatory, and pro-apoptotic activity across multiple cancer cell lines, yet its clinical translation is severely hampered by pharmacokinetic limitations including aqueous solubility below 11 ng/mL at physiological pH, extensive first-pass metabolism, and rapid systemic clearance yielding oral bioavailability typically below 1% in humans. Polymeric nanoparticle encapsulation using mucoadhesive polysaccharides that resist gastric and small intestinal degradation while releasing cargo in the colonic environment — exploiting colonic pH (6.5–7.4) and microbial enzyme-mediated polymer degradation — represents a promising strategy for colon-targeted curcumin delivery. This study reports the preparation, optimisation, and in vitro characterisation of chitosan-sodium alginate nanoparticles (CS-SA NPs) loaded with curcumin via ionic gelation method, investigating the effect of four chitosan:alginate polymer ratios (1:1, 1:2, 2:1, and 1:3 w/w) on encapsulation efficiency (EE%), drug loading capacity (DLC), particle size, zeta potential, polydispersity index (PDI), and in vitro release profile. Optimal formulation (CS:SA = 1:2, designated F3) achieves EE of 84.3 ± 2.1%, particle size 186 ± 12 nm, PDI 0.183, zeta potential -28.4 ± 1.8 mV, and cumulative curcumin release of 78.6% at 24 hours under simulated colonic fluid (pH 6.8, rat caecal content 2% w/v). In vitro cytotoxicity against HCT-116 colon cancer cell line confirms IC50 of 8.4 µg/mL for F3 nanoparticles versus 42.6 µg/mL for free curcumin solution — a 5.1-fold enhancement attributed to nanoparticle-mediated cellular uptake enhancement and sustained intracellular release. FTIR and DSC analysis confirm curcumin encapsulation and polymer-drug compatibility. These results support further in vivo evaluation of CS-SA nanoparticles as a colon-targeted curcumin delivery platform.