Colon cancer is the third most leading causes of death due to cancer worldwide 
and the chemo drug 5-fluorouracil's (5-FU) applicability is limited due to its 
non-specificity, low bioavailability and overdose. The efficacy of 5-FU in colon 
cancer chemo treatment could be improved by nanoencapsulation and combinatorial 
approach. In the present study curcumin (CUR), a known anticancer phytochemical, 
was used in combination with 5-FU and the work focuses on the development of a 
combinatorial nanomedicine based on 5-FU and CUR in N,O-carboxymethyl chitosan 
nanoparticles (N,O-CMC NPs). The developed 5-FU-N,O-CMC NPs and CUR-N,O-CMC NPs 
were found to be blood compatible. The in vitro drug release profile in pH 4.5 
and 7.4 showed a sustained release profile over a period of 4 days. The combined 
exposure of the nanoformulations in colon cancer cells (HT 29) proved the 
enhanced anticancer effects. In addition, the in vivo pharmacokinetic data in 
mouse model revealed the improved plasma concentrations of 5-FU and CUR which 
prolonged up to 72 h unlike the bare drugs. In conclusion, the 5-FU and CUR 
released from the N,O-CMC NPs produced enhanced anticancer effects in vitro and 
improved plasma concentrations under in vivo conditions.