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Cytotoxicity of gemcitabine-loaded thermosensitive liposomes in pancreatic cancer cell lines
Gemcitabine (GEM) is currently the standard option for the treatment of pancreatic cancer but its short half-life and rapid metabolism has caused for new modality for delivery of GEM. The purpose of this study was to formulate GEM loaded PEGylated thermosensitive liposomal nanoparticles (GEM-TSLnps)...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469203/ https://www.ncbi.nlm.nih.gov/pubmed/26090123 |
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author | Affram, Kevin Udofot, Ofonime Agyare, Edward |
author_facet | Affram, Kevin Udofot, Ofonime Agyare, Edward |
author_sort | Affram, Kevin |
collection | PubMed |
description | Gemcitabine (GEM) is currently the standard option for the treatment of pancreatic cancer but its short half-life and rapid metabolism has caused for new modality for delivery of GEM. The purpose of this study was to formulate GEM loaded PEGylated thermosensitive liposomal nanoparticles (GEM-TSLnps) to increase residence time and deliver high payload of GEM to pancreatic cancer cells using mild hyperthermia (mHT). The GEM-TSLnps were formulated by thin film hydration. The cytotoxic effects of GEM and GEM-TSLnps were evaluated against human pancreatic cancer cell lines. In vitro release of GEM by TSLnps was determined at temperatures from 26°C through to 50°C. Cell viability studies, clonogenic assay, flow cytometry and confocal imaging were performed on pancreatic cancer cell lines using GEM and GEM-TSLnps + mHT. The GEM-TSLnp size was determined to be 216.10 ± 0.57 nm with entrapment efficiency of 41.10 ± 2.0%. GEM release from TSLnps was sharply increased at 42°C (60%) than at 37°C (25%), (p<0.01). In vitro cytotoxicity of GEM-TSLnps + mHT treated pancreatic cancer cell lines was significantly higher than GEM treated. The IC50 values for PANC-1, MiaPaCa-2 and BxPC-3 cells GEM-TSLnps + mHT treated were 1.2 to 3.5 fold-higher than GEM treated. Among the cell lines, GEM-TSLnps + mHT treated PANC-1 and MiaPaCa-2 cells show significantly reduced reproductive viability compared with the GEM treated cells. Flow cytometric and confocal images revealed high Rho-TSLnps cellular uptake. Our findings suggest that GEMTSLnps+ mHT can significantly enhance cytotoxic effect of GEM and could serve as a new chemotherapy modality for delivering GEM. |
format | Online Article Text |
id | pubmed-4469203 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-44692032015-06-16 Cytotoxicity of gemcitabine-loaded thermosensitive liposomes in pancreatic cancer cell lines Affram, Kevin Udofot, Ofonime Agyare, Edward Integr Cancer Sci Ther Article Gemcitabine (GEM) is currently the standard option for the treatment of pancreatic cancer but its short half-life and rapid metabolism has caused for new modality for delivery of GEM. The purpose of this study was to formulate GEM loaded PEGylated thermosensitive liposomal nanoparticles (GEM-TSLnps) to increase residence time and deliver high payload of GEM to pancreatic cancer cells using mild hyperthermia (mHT). The GEM-TSLnps were formulated by thin film hydration. The cytotoxic effects of GEM and GEM-TSLnps were evaluated against human pancreatic cancer cell lines. In vitro release of GEM by TSLnps was determined at temperatures from 26°C through to 50°C. Cell viability studies, clonogenic assay, flow cytometry and confocal imaging were performed on pancreatic cancer cell lines using GEM and GEM-TSLnps + mHT. The GEM-TSLnp size was determined to be 216.10 ± 0.57 nm with entrapment efficiency of 41.10 ± 2.0%. GEM release from TSLnps was sharply increased at 42°C (60%) than at 37°C (25%), (p<0.01). In vitro cytotoxicity of GEM-TSLnps + mHT treated pancreatic cancer cell lines was significantly higher than GEM treated. The IC50 values for PANC-1, MiaPaCa-2 and BxPC-3 cells GEM-TSLnps + mHT treated were 1.2 to 3.5 fold-higher than GEM treated. Among the cell lines, GEM-TSLnps + mHT treated PANC-1 and MiaPaCa-2 cells show significantly reduced reproductive viability compared with the GEM treated cells. Flow cytometric and confocal images revealed high Rho-TSLnps cellular uptake. Our findings suggest that GEMTSLnps+ mHT can significantly enhance cytotoxic effect of GEM and could serve as a new chemotherapy modality for delivering GEM. 2015-04-16 2015 /pmc/articles/PMC4469203/ /pubmed/26090123 Text en http://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Article Affram, Kevin Udofot, Ofonime Agyare, Edward Cytotoxicity of gemcitabine-loaded thermosensitive liposomes in pancreatic cancer cell lines |
title | Cytotoxicity of gemcitabine-loaded thermosensitive liposomes in pancreatic cancer cell lines |
title_full | Cytotoxicity of gemcitabine-loaded thermosensitive liposomes in pancreatic cancer cell lines |
title_fullStr | Cytotoxicity of gemcitabine-loaded thermosensitive liposomes in pancreatic cancer cell lines |
title_full_unstemmed | Cytotoxicity of gemcitabine-loaded thermosensitive liposomes in pancreatic cancer cell lines |
title_short | Cytotoxicity of gemcitabine-loaded thermosensitive liposomes in pancreatic cancer cell lines |
title_sort | cytotoxicity of gemcitabine-loaded thermosensitive liposomes in pancreatic cancer cell lines |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469203/ https://www.ncbi.nlm.nih.gov/pubmed/26090123 |
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