Dually sensitive dextran-based micelles for methotrexate delivery. Issue 24 (6th March 2017)

• Record Type: Journal Article
• Authors: Blanco-Fernandez, B.; Concheiro, A.; Makwana, H.; Fernandez-Trillo, F.; Alexander, C.; Alvarez-Lorenzo, C.
• Is Part Of: RSC advances. Volume 7:Issue 24(2017)
• Page Start: 14448
• Page End: 14460
• Publication Date: 2017-03-06
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c7ra00696a
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Temperature and pH-sensitive micelles prepared from dextran grafted with poly( N -isopropylacrylamide) (PNIPAAm)/polyethylene glycol methyl ether (PEGMA) with/without 2-aminoethylmethacrylate (2-AEM) were evaluated as methotrexate delivery systems. 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.