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  • Title: The thermosensitivity of pH/thermoresponsive microspheres activated by the electrostatic interaction of pH-sensitive units with a bioactive compound.
    Author: Fundueanu G, Constantin M, Asmarandei I, Harabagiu V, Ascenzi P, Simionescu BC.
    Journal: J Biomed Mater Res A; 2013 Jun; 101(6):1661-9. PubMed ID: 23184700.
    Abstract:
    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.
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