Ionic Strength-Induced Compartmentalization for Nanogel-in-Microgel Colloids.

Compartmentalization is crucial for control over complex biological cascade reactions. In microgels, the formation of discrete compartments allows for simultaneous uptake and orthogonal release of physicochemically distinct drugs, among others. However, many state-of-the-art approaches yielding compartmentalized microgels require the use of specific, though not always biocompatible, components and temperatures well above the physiological range, which may damage possible biological cargo. Therefore, a novel technique to fabricate compartmentalized microgels by exploiting ionic strength-induced precipitation as a mechanism for compartmentalization is developed. For this, a droplet-based microfluidic approach in which preformed nanogels are incorporated into poly(N-isopropylacrylamide)- or poly(acrylamide)-based microgels is employed. Allowing contact between the nanogel-monomer mixture and a salt solution only at the cross junction inhibits premature precipitation of the nanogels and aggregates form on the chip. It is demonstrated that this method is applicable to a variety of nanogel species in both stimuli-responsive and non-stimuli-responsive microgel networks. For temperature-responsive nanogel compartments in non-responsive microgels, anisotropic shape change is investigated by adjusting temperature or salt concentration or changing the solvent. Lastly, an exemplary uptake and release experiment demonstrates highly selective drug absorption, paving the way for more advanced biomimetic polymer structures.