Issue 24, 2017, Issue in Progress

Dually sensitive dextran-based micelles for methotrexate delivery

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.

Graphical abstract: Dually sensitive dextran-based micelles for methotrexate delivery

Supplementary files

Article information

Article type
Paper
Submitted
17 Jan 2017
Accepted
17 Feb 2017
First published
06 Mar 2017
This article is Open Access
Creative Commons BY license

RSC Adv., 2017,7, 14448-14460

Dually sensitive dextran-based micelles for methotrexate delivery

B. Blanco-Fernandez, A. Concheiro, H. Makwana, F. Fernandez-Trillo, C. Alexander and C. Alvarez-Lorenzo, RSC Adv., 2017, 7, 14448 DOI: 10.1039/C7RA00696A

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