title: In vitro and in vivo biological evaluation of O-carboxymethyl chitosan encapsulated metformin nanoparticles for pancreatic cancer therapy.
abstract: OBJECTIVE
  In vitro anticancer effect and in vivo biodistribution and biocompatibility of metformin encapsulated O-Carboxymethyl chitosan nanoparticles were evaluated for its application as pancreatic cancer therapy.
  
  
  METHODS
  In vitro studies such as cell migration assay, clonogenic assay, cell cycle analysis and qRT-PCR analysis were done in pancreatic cancer cells (MiaPaCa-2) treated with O-CMC-metformin NPs for evaluating its anticancer potential. In vivo biodistribution studies were carried out by NIR imaging of O-CMC-metformin NPs after tagging it with ICG. In vivo biocompatibility of the NPs was assessed by histopathology analysis of organs from mice administered with the NPs.
  
  
  RESULTS
  In vitro cell migration assay showed marginal effect of NPs on migration property of pancreatic cancer cells (MiaPaCa-2). In vitro clonogenic assay established that the O-CMC-metformin NPs reduced colony formation ability of the cancer cells. While cell cycle analysis showed that the O-CMC-metformin NPs had only minor effect on progression of cell cycle in the cancer cells. qRT-PCR analysis exhibited reduced mRNA expression of p21, vanin 1 and MMP9 in pancreatic cancer cells treated with the nanoparticles. In vivo NIR imaging study showed normal biodistribution pattern of the intravenously injected O-CMC-metformin NPs suggesting normal clearance rate of nanoparticles and no adverse toxicity to the organs.
  
  
  CONCLUSIONS
  The biocompatible O-CMC-metformin NPs with anticancer potential and capability for normal biodistribution can be beneficial for the treatment of pancreatic cancer.
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research centre, Kochi, 682041, India.
authors.forename: K S
authors.initials: KS
authors.lastname: Snima
authors.forename: R
authors.initials: R
authors.lastname: Jayakumar
authors.forename: Vinoth-Kumar
authors.initials: VK
authors.lastname: Lakshmanan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D003114:Colony-Forming Units Assay; D004339:Drug Compounding; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008422:Materials Testing; D008687:Metformin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D012333:RNA, Messenger / Q000096:biosynthesis; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; C504164:O-carboxymethylchitosan; D012333:RNA, Messenger; D048271:Chitosan; D008687:Metformin