title: Preclinical efficacy and safety assessment of nano-oxaliplatin oral formulation prepared by novel Fat Employing Supercritical Nano System, the FESNS®.
abstract: BACKGROUND
  It is expected that oral cancer drug will provide ease of administration with decreased unwanted events to the patients. The purpose of this study is to prepare oral formulation of nano-oxaliplatin and examine the anticancer efficacy and safety. Nano-oxaliplatin was prepared utilizing our proprietary technology, the Fat Employing Supercritical Nano System (FESNS(®)).
  
  
  RESULTS
  It showed regular nanoparticles with a mean diameter of around 212 nm. When nano-oxaliplatin was orally administered in rats, the relative bioavailability of nano-oxaliplatin oral formulations was about 25-31% compared to the Eloxatin(®) administered intravenously (i.v.). For antitumor activity in xenograft model, nano-oxaliplatin oral formulation (20 mg/kg, once daily) presented superior inhibition of tumor growth against Eloxatin(®) (5 mg/kg, i.v. once a week). In single-dose toxicity, dead animals were observed at or above 1000 mg/kg (LD(50): 888.38 mg/kg for male; 725.43 mg/kg for female rats). In repeated dose toxicity, there were hematological changes observed in rats, which is a common finding in the class of cancer drugs. It was thought that the expected dose level that has cytotoxic effect without death would be 30 mg/kg in rats, which is double the dose level of Eloxatin(®).
  
  
  CONCLUSIONS
  Nano-oxaliplatin oral formulation changed the pharmacokinetic behavior of crude oxaliplatin, thus increasing oral bioavailability as well as its anticancer activity. In addition, single and repeated dose toxicity studies indicated that oral nano-oxaliplatin is superior in toxicity at the pharmacologically active doses compared to Eloxatin(®) in rats. Nano-oxaliplatin oral formulation has potential as a novel anticancer therapy.
authors.affiliation: Formulation Research Institute, Choongwae Pharma Corporation, Seoul, Republic of Korea.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Seung Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Sang Heon
authors.initials: SH
authors.lastname: Lee
authors.forename: Mikyoung
authors.initials: M
authors.lastname: Hahn
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D019073:HT29 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D000077150:Oxaliplatin; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin