pH-Responsive Micellization of Amphiphilic Diblock Copolymers Synthesized via Reversible Addition−Fragmentation Chain Transfer Polymerization

Abstract

Well-defined poly(sodium 2-(acrylamido)-2-methylpropanesulfonate-block-sodium 6-acrylamidohexanoate) (pNaAMPS-AaH) was synthesized by reversible addition−fragmentation chain transfer (RAFT) radical polymerization of sodium 6-acrylamidohexanoate (AaH) using the sodium 2-(acrylamido)-2-methylpropanesulfonate-based macrochain transfer agent. The “living” polymerization of AaH was evidenced by the fact that the number-average molecular weight increased linearly with monomer conversion while the molecular weight distribution remained narrow independent of the conversion. pH-induced association and dissociation behavior of the diblock copolymers was investigated by quasi-elastic light scattering (QELS), static light scattering (SLS), 1H NMR spin−spin relaxation time, and fluorescence probe techniques. At pH < 4, the diblock copolymers exhibited large values of the hydrodynamic radius and small values of the 1H NMR spin−spin relaxation time. These observations indicated that micellization occurred to form polymer micelles comprising hydrophobic protonated AaH cores and hydrophilic NaAMPS coronas at pH < 4. On the other hand, these diblock copolymers dissolved in aqueous solutions as a state of unimer under high-pH conditions. 8-Anilino-1-naphthalenesulfonic acid, ammonium salt hydrate (ANS), as a fluorescence probe could be incorporated into the protonated AaH core of diblock copolymer micelles at low pH and released upon dissociation of the micelles at high pH, which was completely reversible.

pH-Responsive Intra- and Inter-Molecularly Micelle Formation of Anionic Diblock Copolymer in Water

“…The results for characteristics of PAMPS-PAaU are listed in Table 1. The M w /M n value of PAMPS-PAaU is relatively small (M w /M n = 1.23), predicting that the controlled/living polymerization proceeded successfully [11]. Table 1.…”

“…The experimental data indicated that PAMPS-PAaH forms polymer micelles conditions. The pH-induced association and dissociation are completely reversible without hysteresis [11].…”

Development of acid-sensitive copolymer micelles for drug delivery

“…This can be problematic for biological applications, since it is usually desirable to have stable micelles during circulation in the blood at pH 7.4. For example, poly[sodium 2-(acrylamido)-2-methylpropanesulfonate-block-poly(sodium 6-acrylamidohexanoate)] and poly(sodium 4-styrenesulfonate)-block-poly(sodium 4-vinylbenzoate) form micelles at acidic pHs less than 5, but exist as unimers at and near neutral pH [27,28]. Hydroxyethylcellulose-graft-poly(acrylic acid) (HEC-g-PAA) forms micellar aggregates at pH less than 4 [29].…”

Synthesis and characterization of the PEG‐based nonionic surfactants endowed with carboxylic acid moiety at the hydrophobic terminal

“…[1][2][3][4][5][6][7][8] The pH-responsive behavior is driven by the charge of the carboxylic acid moiety in the hydrophobic micellar core, that is, the collapse of the micelle is caused by electrostatic repulsion between carboxylate ions under neutral to alkaline conditions of aqueous media. The function depends on the molecular design in the polymer structures.…”