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A Novel PAA Derivative with Enhanced Drug Efficacy in Pancreatic Cancer Cell Lines

Nanoparticles have been shown to be effective drug carriers in cancer therapy. Pancreatic cancer forms dense tumours which are often resistant to drug molecules. In order to overcome such multidrug resistance, new drug entities, novel delivery systems and combination therapy strategies are being exp...

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Detalles Bibliográficos
Autores principales: Alsuraifi, Ali, Lin, Paul Kong Thoo, Curtis, Anthony, Lamprou, Dimitrios A., Hoskins, Clare
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315666/
https://www.ncbi.nlm.nih.gov/pubmed/30248980
http://dx.doi.org/10.3390/ph11040091
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author Alsuraifi, Ali
Lin, Paul Kong Thoo
Curtis, Anthony
Lamprou, Dimitrios A.
Hoskins, Clare
author_facet Alsuraifi, Ali
Lin, Paul Kong Thoo
Curtis, Anthony
Lamprou, Dimitrios A.
Hoskins, Clare
author_sort Alsuraifi, Ali
collection PubMed
description Nanoparticles have been shown to be effective drug carriers in cancer therapy. Pancreatic cancer forms dense tumours which are often resistant to drug molecules. In order to overcome such multidrug resistance, new drug entities, novel delivery systems and combination therapy strategies are being explored. In this paper, we report the design and synthesis of a poly(allylamine)-based amphiphile modified with hydrophobic naphthalimido pendant groups. Bisnaphthalimide compounds have been shown to possess anticancer activity. The potential of this polymer to encapsulate, solubilize and enhance drug (5-fluorouricil and bis-(naphthalimidopropyl)-diaminooctane) cytotoxicity in BxPC-3 cells was evaluated. Our studies showed that the insoluble drugs could be formulated up to 4.3 mg mL(−1) and 2.4 mg mL(−1) inside the amphiphiles, respectively. Additionally, the novel poly(allylamine)-naphthalimide carrier resulted in an amplification of cytotoxic effect with drug treatment after 24 h, and was capable of reduction of 50% cell population at concentrations as low as 3 μg mL(−1).
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spelling pubmed-63156662019-01-11 A Novel PAA Derivative with Enhanced Drug Efficacy in Pancreatic Cancer Cell Lines Alsuraifi, Ali Lin, Paul Kong Thoo Curtis, Anthony Lamprou, Dimitrios A. Hoskins, Clare Pharmaceuticals (Basel) Article Nanoparticles have been shown to be effective drug carriers in cancer therapy. Pancreatic cancer forms dense tumours which are often resistant to drug molecules. In order to overcome such multidrug resistance, new drug entities, novel delivery systems and combination therapy strategies are being explored. In this paper, we report the design and synthesis of a poly(allylamine)-based amphiphile modified with hydrophobic naphthalimido pendant groups. Bisnaphthalimide compounds have been shown to possess anticancer activity. The potential of this polymer to encapsulate, solubilize and enhance drug (5-fluorouricil and bis-(naphthalimidopropyl)-diaminooctane) cytotoxicity in BxPC-3 cells was evaluated. Our studies showed that the insoluble drugs could be formulated up to 4.3 mg mL(−1) and 2.4 mg mL(−1) inside the amphiphiles, respectively. Additionally, the novel poly(allylamine)-naphthalimide carrier resulted in an amplification of cytotoxic effect with drug treatment after 24 h, and was capable of reduction of 50% cell population at concentrations as low as 3 μg mL(−1). MDPI 2018-09-22 /pmc/articles/PMC6315666/ /pubmed/30248980 http://dx.doi.org/10.3390/ph11040091 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Alsuraifi, Ali
Lin, Paul Kong Thoo
Curtis, Anthony
Lamprou, Dimitrios A.
Hoskins, Clare
A Novel PAA Derivative with Enhanced Drug Efficacy in Pancreatic Cancer Cell Lines
title A Novel PAA Derivative with Enhanced Drug Efficacy in Pancreatic Cancer Cell Lines
title_full A Novel PAA Derivative with Enhanced Drug Efficacy in Pancreatic Cancer Cell Lines
title_fullStr A Novel PAA Derivative with Enhanced Drug Efficacy in Pancreatic Cancer Cell Lines
title_full_unstemmed A Novel PAA Derivative with Enhanced Drug Efficacy in Pancreatic Cancer Cell Lines
title_short A Novel PAA Derivative with Enhanced Drug Efficacy in Pancreatic Cancer Cell Lines
title_sort novel paa derivative with enhanced drug efficacy in pancreatic cancer cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315666/
https://www.ncbi.nlm.nih.gov/pubmed/30248980
http://dx.doi.org/10.3390/ph11040091
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