Sequential and controlled release of small molecules from poly(N-isopropylacrylamide) microgel-based reservoir devices

Systems composed of a poly(N-isopropylacrylamide)-co-acrylic acid (pNIPAm-co-AAc) microgels (AAc-MG) and poly(N-isopropylacrylamide-3-(acrylamido)phenylboronic acid) (pNIPAm-co-APBA) microgels (APBA-MG) were used to sequentially release small molecules to a system in a controlled and triggered fashion. Specifically, at pH 10.0, methylene blue (MB, positively charged) exhibited strong electrostatic interactions with both the negatively charged AAc and APBA-modified microgels. This resulted in MB uptake into both of the microgels. At pH 7.0, the APBA groups were neutralized, allowing MB to be released from the APBA-MG only. When the solution pH was again lowered to 3.0, the AAc groups are neutralized allowing MB to be released from the AAc-MG. By incorporating the mixed microgels into reservoir devices, and varying their ratio, the small molecule release rate and release amount (dosage) can be easily tuned. Furthermore, two different small molecules can be loaded into the two distinct microgels, which allows for their sequential release at particular pHs. These devices could find use for delivering multiple drugs to a system in a controlled and triggered fashion, which may find a variety of biomedical applications.