Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations

Patrizia Bonelli,1 Franca M Tuccillo,1 Antonella Federico,5 Maria Napolitano,2 Antonella Borrelli,1 Daniela Melisi,6 Maria G Rimoli,6 Raffaele Palaia,3 Claudio Arra,4 Francesco Carinci71Laboratory of Molecular Biology and Viral Oncogenesis; 2Department of Clinical Immunology; 3Department of Gastroin...

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Autores principales: Bonelli P, Tuccillo FM, Federico A, Napolitano M, Borrelli A, Melisi D, Rimoli MG, Palaia R, Arra C, Carinci F
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Publicado: Dove Medical Press 2012
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spelling oai:doaj.org-article:81b1b6f4877d4d21b854c74fd1310f802021-12-02T01:07:54ZIbuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations1176-91141178-2013https://doaj.org/article/81b1b6f4877d4d21b854c74fd1310f802012-11-01T00:00:00Zhttp://www.dovepress.com/ibuprofen-delivered-by-polylactic-co-glycolic-acid-plga-nanoparticles--a11488https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Patrizia Bonelli,1 Franca M Tuccillo,1 Antonella Federico,5 Maria Napolitano,2 Antonella Borrelli,1 Daniela Melisi,6 Maria G Rimoli,6 Raffaele Palaia,3 Claudio Arra,4 Francesco Carinci71Laboratory of Molecular Biology and Viral Oncogenesis; 2Department of Clinical Immunology; 3Department of Gastrointestinal-Hepatobiliary-Pancreatic Cancer Oncology Surgery; 4Animal Facility, National Cancer Institute G Pascale, Naples, Italy; 5Microtech Laboratory, Naples, Italy; 6Pharmaceutical and Toxicological Chemistry Department, School of Pharmacy, University "Federico II", Naples, Italy; 7Department of Maxillofacial Surgery, University of Ferrara, Ferrara, ItalyPurpose: 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.Conclusion: 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.Keywords: nonsteroidal anti-inflammatory drug (NSAID), proliferation, uptake, MKN-45 cellsBonelli PTuccillo FMFederico ANapolitano MBorrelli AMelisi DRimoli MGPalaia RArra CCarinci FDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 5683-5691 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Bonelli P
Tuccillo FM
Federico A
Napolitano M
Borrelli A
Melisi D
Rimoli MG
Palaia R
Arra C
Carinci F
Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations
description Patrizia Bonelli,1 Franca M Tuccillo,1 Antonella Federico,5 Maria Napolitano,2 Antonella Borrelli,1 Daniela Melisi,6 Maria G Rimoli,6 Raffaele Palaia,3 Claudio Arra,4 Francesco Carinci71Laboratory of Molecular Biology and Viral Oncogenesis; 2Department of Clinical Immunology; 3Department of Gastrointestinal-Hepatobiliary-Pancreatic Cancer Oncology Surgery; 4Animal Facility, National Cancer Institute G Pascale, Naples, Italy; 5Microtech Laboratory, Naples, Italy; 6Pharmaceutical and Toxicological Chemistry Department, School of Pharmacy, University "Federico II", Naples, Italy; 7Department of Maxillofacial Surgery, University of Ferrara, Ferrara, ItalyPurpose: 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.Conclusion: 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.Keywords: nonsteroidal anti-inflammatory drug (NSAID), proliferation, uptake, MKN-45 cells
format article
author Bonelli P
Tuccillo FM
Federico A
Napolitano M
Borrelli A
Melisi D
Rimoli MG
Palaia R
Arra C
Carinci F
author_facet Bonelli P
Tuccillo FM
Federico A
Napolitano M
Borrelli A
Melisi D
Rimoli MG
Palaia R
Arra C
Carinci F
author_sort Bonelli P
title Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations
title_short Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations
title_full Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations
title_fullStr Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations
title_full_unstemmed Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations
title_sort ibuprofen delivered by poly(lactic-co-glycolic acid) (plga) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations
publisher Dove Medical Press
publishDate 2012
url https://doaj.org/article/81b1b6f4877d4d21b854c74fd1310f80
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