Dually sensitive dextran-based micelles for methotrexate delivery

Blanco-Fernandez, B.; Concheiro, A.; Makwana, H.; Fernandez-Trillo, Francisco; Alexander, Cameron; Alvarez-Lorenzo, C.

Abstract

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.

Citation

Blanco-Fernandez, B., Concheiro, A., Makwana, H., Fernandez-Trillo, F., Alexander, C., & Alvarez-Lorenzo, C. (2017). Dually sensitive dextran-based micelles for methotrexate delivery. RSC Advances, 7(24), https://doi.org/10.1039/c7ra00696a

• Journal Article Type: Article
• Acceptance Date: Feb 17, 2017
• Publication Date: Mar 6, 2017
• Deposit Date: Jul 12, 2017
• Publicly Available Date: Jul 12, 2017
• Journal: RSC Advances (Deleted)
• Print ISSN: 2046-2069
• Electronic ISSN: 2046-2069
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 24
• DOI: https://doi.org/10.1039/c7ra00696a
• Public URL: https://nottingham-repository.worktribe.com/output/848977
• Publisher URL: http://pubs.rsc.org/en/Content/ArticleLanding/2017/RA/C7RA00696A#!divAbstract