Influence of Buffers, Ionic Strength, and pH on the Volume Phase Transition Behavior of Acrylamide-Based Nanogels

The use of covalently crosslinked nanogels for applications in biology and medicine is dependent on their properties and characteristics, which often change because of the biological media involved. Understanding the role of salts, ionic strength and pH in altering specific properties is key to progress in this area. We studied the effect of both chemical structure and media environment on the thermoresponsive behavior of nanogels. A small library of methylenebisacrylamide (MBA) crosslinked nanogels were prepared using N-isopropylacrylamide (NIPAM) or N-n-propylacrylamide (NPAM), in combination with functional monomers N-hydroxyethylacrylamide (HEAM) and N-acryloyl-l-proline (APrOH). The thermoresponsive properties of nanogels were evaluated in phosphate buffer, tris-acetate buffer and Ringer HEPES, with varying concentrations and ionic strengths. The presence of ions facilitates the phase separation of nanogels, and this “salting-out” effect strongly depends on the electrolyte concentration as well as the specificity of individual anions, e.g., their positions in the Hofmeister series. A subtle change in the chemical structure of the side chain of the monomer from NIPAM to NPAM leads to a reduction of the volume phase transition temperature (VPTT) value by ~10 °C. The addition of hydrophilic comonomers such as HEAM, on the other hand, causes a ~20 °C shift in VPTT to higher values. The data highlight the significant role played by the chemical structure of the monomers used, with hydrophobicity and rigidity closely interlinked in determining thermoresponsive behavior. Furthermore, the volume phase transition temperature (VPTT) of nanogels copolymerized with ionizable APrOH comonomer can be tailored by changes in the pH of buffer solutions. This temperature-controlled phase transition is driven by intricate interplay involving the entropy of mixing, electrostatic interactions, conformational transitions, and structural rigidity. These results highlight the importance of understanding the physiochemical properties and behavior of covalently crosslinked nanogels in a biological environment prior to their applications in life-science, such as temperature/pH-triggered drug delivery systems.

Equilibrium swelling of thermo-responsive copolymer microgels

A model is developed for equilibrium swelling of thermo-responsive copolymer gels and is applied to predict the effect of molar fraction of comonomers on the volume phase transition temperature of macroscopic gels and microgels.

Deuteration-Induced Volume Phase Transition Temperature Shift of PNIPMAM Microgels

The effect of deuteration on the volume phase transition (VPT) temperature of poly (N-isopropylmethacrylamide) (pNIPMAM) microgels in aqueous suspension is determined via IR spectroscopy and size measurements by photon correlation spectroscopy (PCS). We study the effect of a hydrogenated and a deuterated solvent (H2O/D2O), and of the hydrogenated and (partially) deuterated monomer. Deuteration of the monomer or copolymerization with deuterated monomers shifts the volume phase transition temperature (VPTT) by up to 8.4 K to higher temperatures, in good agreement with known results for pNIPAM microgels. Moreover, the shape of the swelling curve is found to depend on deuteration, with the highest deuteration leading to the sharpest VPT. Finally, the quantitative agreement between FTIR spectroscopy and PCS evidences the spatial homogeneity of the microgel particles. Our results are rationalized in terms of the effect of deuteration on hydrogen bonding. They shall be of primary importance for any experimental measurements close to the VPT involving isotopic substitution, and in particular contrast variation small angle neutron scattering.

Thermoresponsive Behavior of Magnetic Nanoparticle Complexed pNIPAm-co-AAc Microgels

Characterization of responsive hydrogels and their enhancement with novel moieties have improved our understanding of functional materials. Hydrogels coupled with inorganic nanoparticles have been sought for novel types of responsive materials, but the efficient routes for the formation and the responsivity of complexed materials remain for further investigation. Here, we report that responsive poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAm-co-AAc) hydrogel microparticles (microgels) are tunable by varying composition of co-monomer and crosslinker as well as by their complexation with magnetic nanoparticles in aqueous dispersions. Our results show that the hydrodynamic diameter and thermoresponsivity of microgels are closely related with the composition of anionic co-monomer, AAc and crosslinker, N,N′-Methylenebisacrylamide (BIS). As a composition of hydrogels, the higher AAc increases the swelling size of the microgels and the volume phase transition temperature (VPTT), but the higher BIS decreases the size with no apparent effect on the VPTT. When the anionic microgels are complexed with amine-modified magnetic nanoparticles (aMNP) via electrostatic interaction, the microgels decrease in diameter at 25 °C and shift the volume phase transition temperature (VPTT) to a higher temperature. Hysteresis on the thermoresponsive behavior of microgels is also measured to validate the utility of aMNP-microgel complexation. These results suggest a simple, yet valuable route for development of advanced responsive microgels, which hints at the formation of soft nanomaterials enhanced by inorganic nanoparticles.

A robust method to calculate the volume phase transition temperature (VPTT) for hydrogels and hybrids

Phase transition temperatures along with system reversibilities defined by a unique reversibility parameter have been developed in this study.