Semi-batch control over functional group distributions in thermoresponsive microgels

Thermosensitive poly(N-isopropylacrylamide-co-methacrylic acid) (poly(NIPAM-co-MAA)) microgels were prepared via semi-batch free radical copolymerization in which the functional monomer (methacrylic acid) was continuously fed into the reaction vessel at various speeds. Microgels with the same bulk MAA contents (and thus the same overall compositions) but different radial functional group distributions were produced, with batch copolymerizations resulting in core-localized functional groups, fast-feed semi-batch copolymerizations resulting in near-uniform functional group distributions, and slow-feed semi-batch copolymerizations resulting in shell-localized functional groups. Functional group distributions in the microgels were probed using titration analysis, electrophoresis, and transmission electron microscopy. The induced functional group distributions have particularly significant impacts on the pH-induced swelling and cationic drug binding behavior of the microgels; slower monomer feeds result in increased pH-induced swelling but lower drug binding. This work suggests that continuous semi-batch feed regimes can be used to synthesize thermoresponsive microgels with well-defined internal morphologies if an understanding of the relative copolymerization kinetics of each comonomer relative to NIPAM is achieved.