Unlocking Curcumin's potential: Nano-encapsulation in mPEG-chitosan/hyaluronic acid complexes for enhanced therapeutic impact in colon cancer

It is known that the instability of curcumin (CUR) and its low solubility restricts its medical application. It is therefore pivotal to improve its chemical stability and solubility. To this end, an attempt was made to manufacture nanoparticles (NPs) containing hyaluronic acid, chitosan, and methoxy polyethylene glycol using the electrostatic complexation method. The shape and morphology of the nanoparticles were confirmed by scanning electron microscopy (SEM). The interaction between the carrier and CUR was evaluated using Fourier transform infrared (FT-IR) and differential scanning calorimetry (DSC). The NPs containing CUR (NPs-CUR) exhibited a round shape with a typical diameter of 164 nm and a zeta potential of −33.9 mV. An encapsulation efficiency of 90.1 % and a drug loading of 7.1 % were achieved. FTIR and DSC analysis showed that CUR was adsorbed on the surface of the NPs. Additionally, the in-vitro release exhibited a sustained release behavior for the CUR-NPs, where 90.34 % of the drug was released within 72 h, in comparison to free CUR, which had a release of 84.75 % within 12 h in simulated colonic fluid (pH 7.4). CUR-NPs at a concentration of 60 μg/mL showed 3 times more potency in the cytotoxicity of Caco-2 cells and demonstrated a greater performance in the uptake efficiency of Caco-2 cells. The results of the real-time PCR indicated that the nano-delivery of CUR remarkably enhanced the expression of genes related to apoptosis while concurrently suppressing genes associated with proliferation in Caco-2 cells. Furthermore, NPs-CUR treatment increased apoptosis as indicated by annexin V staining.