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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
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.
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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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