Impact of Microgel Morphology on Functionalized Microgel−Drug Interactions

The interactions of a range of water-soluble drugs of different charges and hydrophobicities with carboxylic acid-functionalized poly(N-isopropylacrylamide)-based microgels containing different functional group distributions are investigated to determine the impact of drug properties and microgel morphologies on drug uptake and release. The radial distribution of carboxylic acid functional groups in the microgel and the hydrophobicities of the cationic drugs both strongly affect drug partitioning between the solution and microgel phases. Microgels with surface-localized functional group distributions bind less cationic drug than bulk-functionalized microgels, likely due to the formation of a locally collapsed "skin layer" at the acid-base drug binding sites at the microgel surface. In this way, cationic drugs induce a local phase transition that can be used to regulate small molecule diffusion in and out of the gel. As the drug hydrophobicity is increased, the skin layer becomes more condensed and less drug uptake is achieved. In the case of anionic or neutral drugs, high drug uptakes are achieved independent of the functional group distribution within the microgel. High drug uptake is also observed when nonfunctionalized poly(N-isopropylacrylamide) microgels are used as the uptake matrix, suggesting the importance of hydrophobic partitioning in regulating drug-microgel interactions.