title: The thermosensitivity of pH/thermoresponsive microspheres activated by the electrostatic interaction of pH-sensitive units with a bioactive compound.
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.
authors.affiliation: Department of Bioactive and Biocompatible Polymers, Petru Poni Institute of Macromolecular Chemistry, Iasi 700487, Romania. ghefun@icmpp.ro
authors.forename: Gheorghe
authors.initials: G
authors.lastname: Fundueanu
authors.forename: Marieta
authors.initials: M
authors.lastname: Constantin
authors.forename: Ionela
authors.initials: I
authors.lastname: Asmarandei
authors.forename: Valeria
authors.initials: V
authors.lastname: Harabagiu
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.forename: Bogdan C
authors.initials: BC
authors.lastname: Simionescu
mesh_terms: D000180:Acrylic Resins / Q000138:chemical synthesis / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry*; D004008:Diclofenac / Q000737:chemistry / Q000494:pharmacology; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008012:Lidocaine / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009391:Nephelometry and Turbidimetry; D044367:Phase Transition; D055672:Static Electricity; D013696:Temperature
chemical_list: D000180:Acrylic Resins; D001672:Biocompatible Materials; C469412:poly(N-isopropylacrylamide-co-acrylamide); D004008:Diclofenac; D006493:Heparin; D008012:Lidocaine