title: Combinatorial anticancer effects of curcumin and 5-fluorouracil loaded thiolated chitosan nanoparticles towards colon cancer treatment.
abstract: BACKGROUND
  Evaluation of the combinatorial anticancer effects of curcumin/5-fluorouracil loaded thiolated chitosan nanoparticles (CRC-TCS-NPs/5-FU-TCS-NPs) on colon cancer cells and the analysis of pharmacokinetics and biodistribution of CRC-TCS-NPs/5-FU-TCS-NPs in a mouse model.
  
  
  METHODS
  CRC-TCS-NPs/5-FU-TCS-NPs were developed by ionic cross-linking. The in vitro combinatorial anticancer effect of the nanomedicine was proven by different assays. Further the pharmacokinetics and biodistribution analyses were performed in Swiss Albino mouse using HPLC.
  
  
  RESULTS
  The 5-FU-TCS-NPs (size: 150±40nm, zeta potential: +48.2±5mV) and CRC-TCS-NPs (size: 150±20nm, zeta potential: +35.7±3mV) were proven to be compatible with blood. The in vitro drug release studies at pH4.5 and 7.4 showed a sustained release profile over a period of 4 days, where both the systems exhibited a higher release in acidic pH. The in vitro combinatorial anticancer effects in colon cancer (HT29) cells using MTT, live/dead, mitochondrial membrane potential and cell cycle analysis measurements confirmed the enhanced anticancer effects (2.5 to 3 fold). The pharmacokinetic studies confirmed the improved plasma concentrations of 5-FU and CRC up to 72h, unlike bare CRC and 5-FU.
  
  
  CONCLUSIONS
  To conclude, the combination of 5-FU-TCS-NPs and CRC-TCS-NPs showed enhanced anticancer effects on colon cancer cells in vitro and improved the bioavailability of the drugs in vivo.
  
  
  CONCLUSIONS
  The enhanced anticancer effects of combinatorial nanomedicine are advantageous in terms of reduction in the dosage of 5-FU, thereby improving the chemotherapeutic efficacy and patient compliance of colorectal cancer cases.
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, 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 University, Kochi 682041, India.
authors.forename: N
authors.initials: N
authors.lastname: Deepa
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India.
authors.forename: K P
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 University, Kochi 682041, 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 University, Kochi 682041, India. Electronic address: rjayakumar@aims.amrita.edu.
authors.forename: R
authors.initials: R
authors.lastname: Jayakumar
mesh_terms: D000818:Animals; D001682:Biological Availability; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D048271:Chitosan / Q000493:pharmacokinetics / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics / Q000494:pharmacology; D005472:Fluorouracil / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D053758:Nanoparticles
chemical_list: D003692:Delayed-Action Preparations; D048271:Chitosan; D003474:Curcumin; D005472:Fluorouracil
keywords: 5-Fluorouracil; Colon cancer; Combinatorial nanomedicine; Curcumin; Pharmacokinetics; Thiolated chitosan