Poly(N-isopropylacrylamide-co-methacrylic acid) pH/thermo-responsive porous hydrogels as self-regulated drug delivery system.
A dual drug delivery system based on a "biosensor" (pH-sensitive unit) and a delivery component (thermosensitive hydrogel) was developed. The pH/thermosensitive hydrogel is able to restore the thermosensitive characteristics after electrostatic interaction of the pH-sensitive units with selected biologically active compounds that act as triggering agents. The poly(N-isopropylacrylamide-co-methacrylic acid) (poly(NIPAAm-co-MA)) was synthesized as an interesting pH/thermo-responsive copolymer by free radical polymerization method. Due to the presence of carboxylic groups in MA units, the copolymer loses its thermosensitivity at physiological pH and temperature. However, when the negatively-charged carboxylic groups of the pH-sensitive units interact electrostatically with the positively-charged drugs with hydrophobic character propranolol, lidocaine or metoclopramide, taken as model biologically active compounds, the copolymer restores the thermosensitive properties around the physiological pH and temperature. The poly(NIPAAm-co-MA) linear copolymer was converted into pH/thermo-responsive porous microgels using oligomers of NIPAAm above their LCST, as porogens. Accordingly, the swelling/collapsing processes of the microgels occur only after the interaction with the positively-charged hydrophobic drugs. The hydrophobic drug acts as a triggering agent and the pH/temperature sensitive hydrogel turns as a biosensor (pH-sensitive units) and a delivery component (thermosensitive hydrogel).
Department of Natural Polymers, Bioactive and Biocompatible Materials, "Petru Poni" Institute of Macromolecular Chemistry, 700487 Iassy, Romania.
Marieta
M
Constantin
Department of Natural Polymers, Bioactive and Biocompatible Materials, "Petru Poni" Institute of Macromolecular Chemistry, 700487 Iassy, Romania.
Sanda
S
Bucatariu
Department of Natural Polymers, Bioactive and Biocompatible Materials, "Petru Poni" Institute of Macromolecular Chemistry, 700487 Iassy, Romania.
Valeria
V
Harabagiu
Department of Natural Polymers, Bioactive and Biocompatible Materials, "Petru Poni" Institute of Macromolecular Chemistry, 700487 Iassy, Romania.
Irina
I
Popescu
Interdepartmental Laboratory for Electron Microscopy, University Roma Tre, I-00146 Roma, Italy.
Paolo
P
Ascenzi
Department of Natural Polymers, Bioactive and Biocompatible Materials, "Petru Poni" Institute of Macromolecular Chemistry, 700487 Iassy, Romania. Electronic address: ghefun@icmpp.ro.
Gheorghe
G
Fundueanu
D000178:Acrylamides / Q000737:chemistry*; D016503:Drug Delivery Systems; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D011109:Polymethacrylic Acids / Q000737:chemistry*; D016062:Porosity; D013696:Temperature
D000178:Acrylamides; D020100:Hydrogels; D011109:Polymethacrylic Acids; C085085:poly(N-isopropylacrylamide-co-methacrylic acid)
Lower critical solution temperature; Self-regulated drug delivery system; Stimuli-sensitive polymer; Volume phase transition temperature; pH/thermoresponsive copolymer