title: Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations.
abstract: OBJECTIVE
  Epidemiological, clinical, and laboratory studies have suggested that ibuprofen, a commonly used nonsteroidal anti-inflammatory drug, inhibits the promotion and proliferation of certain tumors. Recently, we demonstrated the antiproliferative effects of ibuprofen on the human gastric cancer cell line MKN-45. However, high doses of ibuprofen were required to elicit these antiproliferative effects in vitro. The present research compared the antiproliferative effects of ibuprofen delivered freely and released by poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in MKN-45 cells.
  
  
  METHODS
  MKN-45 human gastric adenocarcinoma cells were treated with ibuprofen-loaded PLGA NPs. The proliferation of MKN-45 cells was then assessed by cell counting. The uptake of NPs was imaged by fluorescence microscopy and flow cytometry. The release of ibuprofen from ibuprofen-loaded PLGA NPs in the cells was evaluated by gas chromatography-mass spectrometry.
  
  
  RESULTS
  Dramatic inhibition of cellular proliferation was observed in cells treated with ibuprofen-loaded PLGA NPs versus those treated with free ibuprofen at the same concentration. The localization of NPs was cytoplasmic. The initiation of ibuprofen release was rapid, commencing within 2 hours, and then increased slowly over time, reaching a maximum concentration at 24 hours. The inhibition of proliferation was confirmed to be due to the intracellular release of ibuprofen from the NPs. Using PLGA NPs as carriers, ibuprofen exerted an antiproliferative activity at concentrations > 100 times less than free ibuprofen, suggesting greater efficiency and less cellular toxicity. In addition, when carried by PLGA NPs, ibuprofen more quickly induced the expression of transcripts involved in proliferation and invasiveness processes.
  
  
  CONCLUSIONS
  Ibuprofen exerted an antiproliferative effect on MKN-45 cells at low concentrations. This effect was achieved using PLGA NPs as carriers of low doses of ibuprofen.
authors.affiliation: Laboratory of Molecular Biology and Viral Oncogenesis, National Cancer Institute G Pascale, Naples, Italy. patrizia.bonelli@virgilio.it
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bonelli
authors.forename: Franca M
authors.initials: FM
authors.lastname: Tuccillo
authors.forename: Antonella
authors.initials: A
authors.lastname: Federico
authors.forename: Maria
authors.initials: M
authors.lastname: Napolitano
authors.forename: Antonella
authors.initials: A
authors.lastname: Borrelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Melisi
authors.forename: Maria G
authors.initials: MG
authors.lastname: Rimoli
authors.forename: Raffaele
authors.initials: R
authors.lastname: Palaia
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
authors.forename: Francesco
authors.initials: F
authors.lastname: Carinci
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage* / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D053769:Nanocapsules; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007052:Ibuprofen