Curcumin-loaded N,O-carboxymethyl chitosan nanoparticles for cancer drug delivery

Abstract

Chitosan (CS) and its carboxymethyl derivatives are smart biopolymers that are non-toxic, biocompatible and biodegradable, and, hence, suitable for various biomedical applications, such as drug delivery, gene therapy and tissue engineering. Curcumin is a major chemotherapeutic agent with antioxidant, anti-inflammatory, anti-proliferative, anticancer and antimicrobial effects. However, the potential of curcumin as a chemotherapeutic agent is limited by its hydrophobicity and poor bioavailability. In this work, we developed a nanoformulation of curcumin in a carboxymethyl chitosan (CMC) derivative, N,O-carboxymethyl chitosan (N,O-CMC). The curcumin-loaded N,O-CMC (curcumin-N,O-CMC) nanoparticles were characterized using DLS, AFM, SEM, FT-IR and XRD. DLS studies revealed nanoparticles with a mean diameter of 150 ± 30 nm. AFM and SEM confirmed that the particles have a spherical morphology within the size range of 150 ± 30 nm. Curcumin was entrapped with in N,O-CMC nanopartcles with an efficiency of 80%. The in vitro drug-release profile was studied at different pH (7.4 and 4.5) at 37°C for different incubation periods with and without lysozyme. Cytotoxicity studies using MTT assay indicated that curcumin-N,O-CMC nanoparticles showed specific toxicity towards cancer cells and non-toxicity to normal cells. Cellular uptake of curcumin-N,O-CMC nanoparticles was analyzed by fluorescence microscopy and was reconfirmed by flow cytometry. Overall, these results indicate that like previously reported curcumin loaded O-CMC nanoparticles, N,O-CMC will also be an efficient nanocarrier for delivering curcumin to cancer cells.

Keywords: N,O-Carboxymethyl chitosan; cancer drug delivery; cellular uptake; curcumin; cytotoxicity; nanoformulation.