Controlled\nDrug Release from the Aggregation–Disaggregation\nBehavior of pH-Responsive Microgels

Abstract

In this submission, two independent\nsets of microgels were synthesized\nthat exhibit pH responsivity over different solution pH ranges. The\nmicrogels were synthesized by copolymerizing two different comonomers\nwith poly­(<i>N</i>-isopropylacrylamide) (pNIPAm). The microgels\ncopolymerized with acrylic acid exhibit a negative charge above pH\n4.25, while the microgels copolymerized with <i>N</i>-[3-(dimethylamino)­propyl]­methacrylamide\nexhibit a positive charge below pH 8.4; these microgels are neutral\noutside of these pH ranges. We show that aggregates form when the\ntwo independent sets of microgels are exposed to one another in a\nsolution that renders them both charged. Furthermore, in solutions\nof pH outside of this range, the microgels disaggregate because one\nof the microgels becomes neutralized. This behavior was exploited\nto load (aggregation) and release (disaggregation) a small-molecule\nmodel drug, methylene blue. This aggregate-based system is one example\nof how pNIPAm-based microgels can be used for controlled/triggered\ndrug delivery, which can have implications for therapeutics.