Influence of Nanoaggregation Routes on the Structure and Thermal Behavior of Multiple-Stimuli-Responsive Micelles from Block Copolymers of Oligo(ethylene glycol) Methacrylate and the Weak Acid [2-(Hydroxyimino)aldehyde]butyl Methacrylate.

In this work, we compare nanoaggregation driven by pH-induced micellization (PIM) and by the standard solvent displacement (SD) method on a series of pH-, light-, and thermosensitive amphiphilic block copolymers. Specifically, we investigate poly(HIABMA)-b-poly(OEGMA) and poly(HIABMA)-b-poly(DEGMA-r-OEGMA), where HIABMA = [(hydroxyimino)aldehyde]butyl methacrylate, OEGMA = oligo(ethylene glycol)methyl ether methacrylate, and DEGMA = di(ethylene glycol)methyl ether methacrylate. The weakly acidic HIA group (pKa ≈ 8) imparts stability to micelles at neutral pH, unlike most of the pH-responsive copolymers investigated in the literature. With SD, only some of our copolymers yield polymeric micelles (34-59 nm), and their thermoresponsivity is either poor or altogether absent. In contrast, PIM affords thermoresponsive, smaller micelles (down to 24 nm), regardless of the polymer composition. In some cases, cloud points are remarkably well defined and exhibit limited hysteresis. By combining turbidimetric, dyamic light scattering, and small-angle X-ray scattering measurements, we show that SD yields loose micelles with POEGMA segments partly involved in the formation of the hydrophobic core, whereas PIM yields more compact core-shell micelles with a well-defined PHIABMA core. We conclude that pH-based nanoaggregation provides advantages over block-selective solvation to obtain compact micelles exhibiting well-defined responses to external stimuli.