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Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells
Traditional anticancer chemotherapy often displays toxic side effects, poor bioavailability, and a low therapeutic index. Targeting and controlled release of a chemotherapeutic agent can increase drug bioavailability, mitigate undesirable side effects, and increase the therapeutic index. Here we rep...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496003/ https://www.ncbi.nlm.nih.gov/pubmed/26167335 http://dx.doi.org/10.1155/2013/932797 |
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author | Sood, Nimil Jenkins, Walter T. Yang, Xiang-Yang Shah, Nikesh N. Katz, Joshua S. Koch, Cameron J. Frail, Paul R. Therien, Michael J. Hammer, Daniel A. Evans, Sydney M. |
author_facet | Sood, Nimil Jenkins, Walter T. Yang, Xiang-Yang Shah, Nikesh N. Katz, Joshua S. Koch, Cameron J. Frail, Paul R. Therien, Michael J. Hammer, Daniel A. Evans, Sydney M. |
author_sort | Sood, Nimil |
collection | PubMed |
description | Traditional anticancer chemotherapy often displays toxic side effects, poor bioavailability, and a low therapeutic index. Targeting and controlled release of a chemotherapeutic agent can increase drug bioavailability, mitigate undesirable side effects, and increase the therapeutic index. Here we report a polymersome-based system to deliver gemcitabine to Panc-1 cells in vitro. The polymersomes were self-assembled from a biocompatible and completely biodegradable polymer, poly(ethylene oxide)-poly(caprolactone), PEO-PCL. We showed that we can encapsulate gemcitabine within stable 200 nm vesicles with a 10% loading efficiency. These vesicles displayed a controlled release of gemcitabine with 60% release after 2 days at physiological pH. Upon treatment of Panc-1 cells in vitro, vesicles were internalized as verified with fluorescently labeled polymersomes. Clonogenic assays to determine cell survival were performed by treating Panc-1 cells with varying concentrations of unencapsulated gemcitabine (FreeGem) and polymersome-encapsulated gemcitabine (PolyGem) for 48 hours. 1 μM PolyGem was equivalent in tumor cell toxicity to 1 μM FreeGem, with a one log cell kill observed. These studies suggest that further investigation on polymersome-based drug formulations is warranted for chemotherapy of pancreatic cancer. |
format | Online Article Text |
id | pubmed-4496003 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-44960032015-07-08 Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells Sood, Nimil Jenkins, Walter T. Yang, Xiang-Yang Shah, Nikesh N. Katz, Joshua S. Koch, Cameron J. Frail, Paul R. Therien, Michael J. Hammer, Daniel A. Evans, Sydney M. J Pharm (Cairo) Research Article Traditional anticancer chemotherapy often displays toxic side effects, poor bioavailability, and a low therapeutic index. Targeting and controlled release of a chemotherapeutic agent can increase drug bioavailability, mitigate undesirable side effects, and increase the therapeutic index. Here we report a polymersome-based system to deliver gemcitabine to Panc-1 cells in vitro. The polymersomes were self-assembled from a biocompatible and completely biodegradable polymer, poly(ethylene oxide)-poly(caprolactone), PEO-PCL. We showed that we can encapsulate gemcitabine within stable 200 nm vesicles with a 10% loading efficiency. These vesicles displayed a controlled release of gemcitabine with 60% release after 2 days at physiological pH. Upon treatment of Panc-1 cells in vitro, vesicles were internalized as verified with fluorescently labeled polymersomes. Clonogenic assays to determine cell survival were performed by treating Panc-1 cells with varying concentrations of unencapsulated gemcitabine (FreeGem) and polymersome-encapsulated gemcitabine (PolyGem) for 48 hours. 1 μM PolyGem was equivalent in tumor cell toxicity to 1 μM FreeGem, with a one log cell kill observed. These studies suggest that further investigation on polymersome-based drug formulations is warranted for chemotherapy of pancreatic cancer. Hindawi Publishing Corporation 2013 2013-06-23 /pmc/articles/PMC4496003/ /pubmed/26167335 http://dx.doi.org/10.1155/2013/932797 Text en Copyright © 2013 Nimil Sood et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Sood, Nimil Jenkins, Walter T. Yang, Xiang-Yang Shah, Nikesh N. Katz, Joshua S. Koch, Cameron J. Frail, Paul R. Therien, Michael J. Hammer, Daniel A. Evans, Sydney M. Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells |
title | Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells |
title_full | Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells |
title_fullStr | Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells |
title_full_unstemmed | Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells |
title_short | Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells |
title_sort | biodegradable polymersomes for the delivery of gemcitabine to panc-1 cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496003/ https://www.ncbi.nlm.nih.gov/pubmed/26167335 http://dx.doi.org/10.1155/2013/932797 |
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