Volume Transition and Phase Coexistence in Polyelectrolyte Gels Interacting with Amphiphiles and Proteins

Abstract

Polyelectrolyte gels have the capacity to absorb large amounts of multivalent species of opposite charge from aqueous solutions of low ionic strength, and release them at elevated ionic strengths. The reversibility offers the possibility to switch between “storage” and “release” modes, useful in applications such as drug delivery. The review focuses on systems where so-called volume phase transitions (VPT) of the gel network take place upon the absorption and release of proteins and self-assembling amphiphiles. We discuss the background in terms of thermodynamic driving forces behind complex formation in oppositely charged mixtures, the role played by cross-links in covalent gels, and general aspects of phase coexistence in networks in relation to Gibbs’ phase rule. We also briefly discuss a gel model frequently used in papers covered by the review. After that, we review papers dealing with collapse and swelling transitions of gels in contact with solution reservoirs of macroions and surfactants. Here we describe recent progress in our understanding of the conditions required for VPT, competing mechanisms, and hysteresis effects. We then review papers addressing equilibrium aspects of core–shell phase coexistence in gels in equilibrium. Here we first discuss early observations of phase separated gels and results showing how the phases affect each other. Then follows a review of recent theoretical and experimental studies providing evidence of thermodynamically stable core–shell phase separated states, and detailed analyses of the conditions under which they exist. Finally, we describe the results from investigations of mechanisms and kinetics of the collapse/swelling transitions induced by the loading/release of proteins, surfactants, and amphiphilic drug molecules.

Antiseptic Polymer–Surfactant Complexes with Long-Lasting Activity against SARS-CoV-2

“…We observed that the formation of collapsed shells could be avoided if the concentration of CPC solution used for loading is rather low (for instance, lower than 0.25 M for PAAm-AMPSA-4s hydrogel). Note that, in these experiments, we tried to avoid the formation of dense shells of polymer-surfactant complex, which are observed when the surface region collapses because of complex formation, whereas the central part of the gel remains in the swollen state [47][48][49][50]. Such collapsed shells release a considerable amount of CPC, so that the disinfectant is quickly exhausted, shortening the antiseptic activity of the material.…”

Drug-Induced Phase Separation in Polyelectrolyte Microgels

“…In many applications the polyelectrolyte networks are spherical microgel particles with diameters in the range 10–1000 µm. There are a number of research papers showing that proteins and peptides can be loaded onto such microgels at low ionic strength and subsequently released at elevated ionic strengths [ 4 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. The electrostatic interaction with the charged network does not seem to denature the molecules; instead the environment inside the microgel has been shown to protect them against degrading species [ 34 , 35 ].…”

“…The electrostatic interaction with the charged network does not seem to denature the molecules; instead the environment inside the microgel has been shown to protect them against degrading species [ 34 , 35 ]. The reversible loading-release property is particularly efficient for multivalent proteins and species forming aggregates of multivalent charge, such as micelle forming surfactants [ 28 , 31 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. At low ionic strength the gain in entropy from replacing a large number of network counterions with a small number of multivalent species provides a strong driving force for binding.…”

Re-Entrant Conformation Transition in Hydrogels

“…Tanaka’s work has stimulated a huge interest in the theoretical and experimental studies on the volume phase transition in hydrogels [ 1 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Because the additional ionic term in eq 1 significantly affects the swelling properties, the existence of ionic groups facilitates the volume phase transition in hydrogels.…”

“…Many synthetic and biological hydrogels containing ionic groups exhibit a reversible discontinuous volume phase transition depending on the external stimuli such as temperature, pH, composition of the solvent, etc. [ 1 , 15 , 17 , 19 , 20 , 23 , 24 , 25 ]. Because the external stimuli affect the extent of polymer–solvent interactions, the volume phase transition occurs due to the change of the χ parameter of polymer–solvent system.…”