Covalently cross-linked and hydrolytically degradable poly(oligoethylene glycol methacrylate) (POEGMA)-based nanogels are fabricated using an all-aqueous self-assembly approach. The nanogels are
composed of hydrazide- (POH) and aldehyde-functionalized (POA) POEGMA precursor polymers that exhibit lower critical solution temperature (LCST) behavior in aqueous media and form a covalent, yet
degradable, hydrazone linkage upon mixing. By systematically changing the chemistry of the core and cross-linking precursor polymers, the concentration of the core precursor polymer, the ratio of
core to cross-linking precursor polymer, and the temperature at which the assembly is conducted, a library of nanogels was produced with significant differences in size, polydispersity, and colloidal
stability. Multivariate statistics indicates the presence of significant nonlinear responses within the process variables as well as correlations between the output variables, reflective of the
complex balance of aggregation and stabilization mechanisms at play to produce a stable, monodisperse nanogel population. Furthermore, formulations that yield more polydisperse nanogels on a small
scale result in macroscopic aggregate formation when scaled up while formulations that yield more monodisperse nanogels can be scaled to yield nanogels with matched properties. We anticipate these
results can be applied to strategically synthesize stable, covalently cross-linked, degradable nanogels with targeted sizes at scalable quantities for a range of biomedical and biosensing
applications.
