Dually sensitive dextran-based micelles for methotrexate delivery

Temperature-sensitive polymeric micelles were prepared from dextran grafted with poly(N-isopropylacrylamide) (PNIPAAm) or polyethylene glycol methyl ether (PEGMA) via controlled radical polymerization and evaluated as delivery systems of the anticancer drug methotrexate (MTX). Polymer-grafting was c...

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Main Authors: Blanco-Fernandez, B., Concheiro, A., Makwana, H., Fernandez-Trillo, Francisco, Alexander, Cameron, Alvarez-Lorenzo, C.
Format: Article
Published: Royal Society of Chemistry 2017
Online Access:https://eprints.nottingham.ac.uk/44129/
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author Blanco-Fernandez, B.
Concheiro, A.
Makwana, H.
Fernandez-Trillo, Francisco
Alexander, Cameron
Alvarez-Lorenzo, C.
author_facet Blanco-Fernandez, B.
Concheiro, A.
Makwana, H.
Fernandez-Trillo, Francisco
Alexander, Cameron
Alvarez-Lorenzo, C.
author_sort Blanco-Fernandez, B.
building Nottingham Research Data Repository
collection Online Access
description Temperature-sensitive polymeric micelles were prepared from dextran grafted with poly(N-isopropylacrylamide) (PNIPAAm) or polyethylene glycol methyl ether (PEGMA) via controlled radical polymerization and evaluated as delivery systems of the anticancer drug methotrexate (MTX). Polymer-grafting was carried out after introduction of initiating groups onto the polysaccharide backbone, without the need for protection of hydroxyl groups and avoiding the use of toxic solvents. Temperature-responsive dextran-based copolymers were designed to exhibit self-aggregation behaviour, affinity for MTX and high cellular internalization. In addition, some grafted polymers incorporated 2-aminoethyl methacrylate to reinforce MTX encapsulation in the micelles by means of ionic interactions. Dextran-based micelles were cytocompatible and had an appropriate size to be used as drug carriers. MTX release was dependent on the pH and temperature. The combination of poly(2-aminoethylmethacrylate) and PNIPAAm with the dextran backbone permitted the complete release of MTX at normal physiological temperature. Co-polymer micelles were highly internalized by tumour cells (CHO-K1) and, when loaded with MTX, led to enhanced cytotoxicity compared to the free drug.
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spelling nottingham-441292020-05-04T18:36:51Z https://eprints.nottingham.ac.uk/44129/ Dually sensitive dextran-based micelles for methotrexate delivery Blanco-Fernandez, B. Concheiro, A. Makwana, H. Fernandez-Trillo, Francisco Alexander, Cameron Alvarez-Lorenzo, C. Temperature-sensitive polymeric micelles were prepared from dextran grafted with poly(N-isopropylacrylamide) (PNIPAAm) or polyethylene glycol methyl ether (PEGMA) via controlled radical polymerization and evaluated as delivery systems of the anticancer drug methotrexate (MTX). Polymer-grafting was carried out after introduction of initiating groups onto the polysaccharide backbone, without the need for protection of hydroxyl groups and avoiding the use of toxic solvents. Temperature-responsive dextran-based copolymers were designed to exhibit self-aggregation behaviour, affinity for MTX and high cellular internalization. In addition, some grafted polymers incorporated 2-aminoethyl methacrylate to reinforce MTX encapsulation in the micelles by means of ionic interactions. Dextran-based micelles were cytocompatible and had an appropriate size to be used as drug carriers. MTX release was dependent on the pH and temperature. The combination of poly(2-aminoethylmethacrylate) and PNIPAAm with the dextran backbone permitted the complete release of MTX at normal physiological temperature. Co-polymer micelles were highly internalized by tumour cells (CHO-K1) and, when loaded with MTX, led to enhanced cytotoxicity compared to the free drug. Royal Society of Chemistry 2017-03-06 Article PeerReviewed Blanco-Fernandez, B., Concheiro, A., Makwana, H., Fernandez-Trillo, Francisco, Alexander, Cameron and Alvarez-Lorenzo, C. (2017) Dually sensitive dextran-based micelles for methotrexate delivery. RSC Advances, 7 (24). pp. 14448-14460. ISSN 2046-2069 http://pubs.rsc.org/en/Content/ArticleLanding/2017/RA/C7RA00696A#!divAbstract doi:10.1039/c7ra00696a doi:10.1039/c7ra00696a
spellingShingle Blanco-Fernandez, B.
Concheiro, A.
Makwana, H.
Fernandez-Trillo, Francisco
Alexander, Cameron
Alvarez-Lorenzo, C.
Dually sensitive dextran-based micelles for methotrexate delivery
title Dually sensitive dextran-based micelles for methotrexate delivery
title_full Dually sensitive dextran-based micelles for methotrexate delivery
title_fullStr Dually sensitive dextran-based micelles for methotrexate delivery
title_full_unstemmed Dually sensitive dextran-based micelles for methotrexate delivery
title_short Dually sensitive dextran-based micelles for methotrexate delivery
title_sort dually sensitive dextran-based micelles for methotrexate delivery
url https://eprints.nottingham.ac.uk/44129/
https://eprints.nottingham.ac.uk/44129/
https://eprints.nottingham.ac.uk/44129/