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).

Graphical abstractSchematic representation of the principle of operation of pH/thermosensitive poly(NIPAAm-co-MA) microgels in the presence of the triggering agent, under simulated physiological conditions.Figure optionsDownload full-size imageDownload high-quality image (135 K)Download as PowerPoint slide