Sulfonate-functionalized ionic liquids for pH-sensitive alginate beads preparation: Macromolecular structure study and drug release evaluation

Abstract

Aiming at a new application of ionic liquids in the formation of biomaterials, polymeric hydrogel beads sensitive to pH were produced based on alginate, using sulfonate ionic liquids (ILs) in a novel way as crosslinking agents. Among the tested ILs, the new functionalized IL A1 [1-(4-ethoxy-1-butylsulfonic)-3-methylimidazolium bromide] was synthesized for the first time. The IL A1 and the IL A2 (triethylammonium hydrogen sulfate) resulted in the formation of beads by drip method. Their structural representation was obtained from the molecular docking, allowing a study of their molecular interactions. Tests of variation in the degree of swelling showed that under pH 6.0 and 7.4, the beads dissolved in a few minutes; while under pH 1.2, they remain stable for at least 7 h. The lower degree of swelling in relation to time obtained for the systems resulted in beads with more compact structures, when compared to swelled beads formed with alginate and conventional bivalents ions. Cumulative release point of 5-fluorouracil and indomethacin remained sustained until at least 8 h, under pH 1.2. The lower energy conformations were calculated for each macromolecule combination of bead-drug, and was obtained that the 5-fluorouracil interacts more strongly with the beads structural network than indomethacin, resulting in a slower release that reached 9.84% (w/w) against 25.00% (w/w). These results indicate a potential application for the ionic liquids-beads as a site-specific drug carrier.