title: In vitro combinatorial anticancer effects of 5-fluorouracil and curcumin loaded N,O-carboxymethyl chitosan nanoparticles toward colon cancer and in vivo pharmacokinetic studies.
abstract: 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.
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, India.
authors.forename: A
authors.initials: A
authors.lastname: Anitha
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, India.
authors.forename: Maya
authors.initials: M
authors.lastname: Sreeranganathan
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, India.
authors.forename: Krishna Prasad
authors.initials: KP
authors.lastname: Chennazhi
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, India.
authors.forename: Vinoth-Kumar
authors.initials: VK
authors.lastname: Lakshmanan
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, India. Electronic address: rjayakumar@aims.amrita.edu.
authors.forename: R
authors.initials: R
authors.lastname: Jayakumar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D001777:Blood Coagulation; D002453:Cell Cycle; D002460:Cell Line; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003474:Curcumin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019073:HT29 Cells; D006461:Hemolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; C077199:O,N-carboxymethylchitosan; D048271:Chitosan; D003474:Curcumin; D005472:Fluorouracil
keywords: 5-Fluorouracil (5-FU); Colon cancer; Combinatorial approach; Curcumin (CUR); Drug delivery; N,O-carboxymethyl chitosan nanoparticles (N,O-CMC NPs); Pharmacokinetics