pH-Regulated Controlled Swelling and Sustained Release from the Core Functionalized Amphiphilic Block Copolymer Micelle.

pH-responsive amphiphilic block copolymers based on poly(ethylene glycol)monomethyl ether--poly(methyl methacrylate--methacrylamidepropanoic acid) (PEO--PMMA--PMAPA) with different MMA/MAPA ratios were synthesized from respective amine-reactive prepolymers based on poly(ethylene glycol)monomethyl ether--poly(methyl methacrylate--methacryloxysuccinimide) (PEO--PMMA--PMASI) in such a way that the pH-responsive carboxylic acid groups were randomly distributed in the hydrophobic (PMMA) block. In aqueous medium, they formed micellar aggregates. Control experiments showed stability and critical aggregation concentration and dye encapsulation properties were better for carboxylic acid functionalized micelles at acidic pH compared to a structurally similar block copolymer micelle that lacked any carboxylic acid group. This was attributed to H-bonding among the carboxylic acid groups. In basic pH upon deprotonation, controlled swelling of the aggregates was observed due to repulsion among the negatively charged carboxylate groups. The extent of swelling/deswelling was well controlled by simply changing the percentage of the pH-responsive units in the hydrophobic block and could be probed quantitatively by pH-dependent dynamic light scattering (DLS) and fluorescence resonance energy transfer (FRET) studies. The aggregates were able to encapsulate a hydrophobic guest such as pyrene at the interior of the micelle, and sustained release of this hydrophobic probe was achieved selectively at basic pH due to swelling of the micelles instead of complete disassembly that generally leads to burst release.