How to cite this article: Fundueanu G, Constantin M, Asmarandei I, Harabagiu V, Ascenzi P, Simionescu BC. 2013. The thermosensitivity of pH/thermoresponsive microspheres activated by the electrostatic interaction of pH-sensitive units with a bioactive compound. J Biomed Mater Res Part A 2013:101A:1661–1669.
The thermosensitivity of pH/thermoresponsive microspheres activated by the electrostatic interaction of pH-sensitive units with a bioactive compound†
Article first published online: 27 NOV 2012
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Biomedical Materials Research Part A
Volume 101A, Issue 6, pages 1661–1669, June 2013
How to Cite
Fundueanu, G., Constantin, M., Asmarandei, I., Harabagiu, V., Ascenzi, P. and Simionescu, B. C. (2013), The thermosensitivity of pH/thermoresponsive microspheres activated by the electrostatic interaction of pH-sensitive units with a bioactive compound. J. Biomed. Mater. Res., 101A: 1661–1669. doi: 10.1002/jbm.a.34469
- Issue published online: 13 APR 2013
- Article first published online: 27 NOV 2012
- Manuscript Accepted: 21 SEP 2012
- Manuscript Revised: 18 SEP 2012
- Manuscript Received: 16 MAY 2012
- European Social Fund—“Cristofor I. Simionescu” Postdoctoral Fellowship Programme (ID POSDRU/89/1.5/S/55216), Sectoral Operational Programme Human Resources Development 2007–2013
- sensor-based self-regulated drug delivery system;
- pH/thermoresponsive copolymers;
- smart polymers;
- stimuli-sensitive polymers;
- lower critical solution temperature
pH/thermosensitive hydrogels whose thermosensitivity is activated by the electrostatic interaction of the pH-sensitive units with a hydrophobic bioactive compound are proposed here as sensor-based self-regulated drug delivery systems. Poly(N-isopropylacrylamide-co-acrylamide-co-aminoethylacrylamide) (poly(NIPAAm-co-AAm-co-AEAAm)) was prepared as a new pH/thermoresponsive polymer by hydrolysis of poly(N-isopropylacrylamide-co-acrylamide (poly(NIPAAm-co-AAm)) at high temperature (120°C) in the presence of ethylenediamine. Owing to the hydrophilicity of the inserted amine, the copolymers lose the thermosensitivity at physiological temperature and have a slow-phase transition at temperatures much higher than that of the human body. However, when the positively charged amine groups of the pH-sensitive units bind electrostatically with the negatively charged drug diclofenac, the copolymers retrieve the thermosensitivity. Poly(NIPAAm-co-AAm-co-AEAAm) was transformed into pH/thermoresponsive stable microspheres by an original approach based on crosslinking of the amine groups of aminoethylacrylamide (AEAAm) with glutaraldehyde at a temperature slightly below the lower critical solution temperature. The swelling/deswelling processes of microspheres occur only after the interaction of poly(NIPAAm-co-AAm-co-AEAAm) with the negatively charged drug diclofenac. The pH/temperature-sensitive microgels and dicofenac act as sensors and as the triggering agent, respectively. Conductometric titration reveals that the thermosensitivity of poly(NIPAAm-co-AAm-co-AEAAm) is retrieved when just half of its amino groups are complexed with diclofenac. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.