Water-based synthesis of cationic hydrogel particles: effect of the reaction parameters and in vitro cytotoxicity study

Abstract

Micro/nanoscale hydrogel particles are of great interest for biomedical applications, such as carriers for therapeutic delivery. Compared to conventional hydrogel particles that are mainly composed of vinylic monomers, we have introduced a simple methodology to prepare multi-functional cationic hydrogel particles by adopting the epoxy-amine chemistry in water exemplifying "click" characteristics. Herein, we investigate the effects of key reaction parameters, including time, temperature, reactant concentration and amine-epoxy stoichiometric ratio, on the preparation and properties of such hydrogel particles. Our results indicated that the aforementioned parameters could greatly impact the particle formation. The hydrodynamic diameter, surface charge, and morphology of the resultant particles were characterized by dynamic light scattering and scanning electron microscopy. Particle size was inversely correlated with the following reaction parameters: reaction time, temperature, and reactant concentration. This is likely due to the influence of the parameters on the formation of the intermediate thermosensitive prepolymers. Different reaction conditions yielded a wide range of particle surface charges, varying from +47 mV to +71 mV. Morphological analysis also revealed significant effects induced by the variation of reaction time and temperature. All particles exhibited a temperature-dependent swelling property.However, the extent of swelling and sensitivity varied depending on the reaction conditions. Finally, in vitro cytocompatibility studies based on murine RAW264.7 macrophages showed the particle acute cytotoxicity being dose and surface charge dependent. Cytocompatibility of the cationic hydrogel particles was improved by reducing the surface charges with variation of the synthesis conditions. † Electronic supplementary information (ESI) available: SEM images of products collected from reactions based on amino hydrogen to epoxy stoichiometric ratios of 0.5 and 1; thermal responsiveness of the monomer JT403; intensity correlation curves of various hGPs; transmission electron microscopy (TEM) images of hGPs prepared using different reaction times; hGP stability in serum-containing culture medium; and phase contrast image of the non-treated macrophage control culture. See

Complexation-induced resolution enhancement of 3D-printed hydrogel constructs

“…In general, positively charged hydrogels are less frequently utilized and are typically adopted for situations where their charge is key for the application (a feature that would be negated by our complexation-based technique). Moreover, cationic hydrogels in general are more cytotoxic 16 and therefore less commonly used for applications intended to grow cells in before charge neutralization. Therefore, we intended to focus more on the shrinking abilities of negatively charged hydrogels (i.e., HAMA, GelMA, and alginate), with a brief demonstration also on the shrinking of positively charged hydrogels (chitosan).…”

Facile Use of Cationic Hydrogel Particles for Surface Modification of Planar Substrates Toward Multifunctional Neural Permissive Surfaces: An in Vitro Investigation

“…Among the various types of HPs that have been reported to date, we selected the one prepared from monomers of bisepoxide and aliphatic polyetheramine largely because of the cationic characteristic of the resulting particles and the ease of preparation. , For neuronal cultures, it is widely shown that surface treatments of culture substrates with cationic polymers such as polylysine, polyornithine, or PEI can greatly improve neuron adhesion to the substrates. , Thus, HPs carrying positive charges can provide a chemical-cue based strategy to modulate neuron adhesion. As shown in Figure , the prepared HPs used in this study have an average surface charge of +60 mV with intensity average hydrodynamic diameter being 410 nm based on DLS measurements.…”

“…The details of the hydrogel particle (HP) preparation have been described elsewhere. , Briefly, Jeffamine T-403 polyetheramine (Huntsman) and 1,3-butadiene diepoxide (Aldrich) were mixed at the molar ratio of 2:3 (Jeffamine/diepoxide) to a final monomer concentration of 15 wt % in water. The resulting solution was first incubated at 65 °C for 10 min before it was diluted to 0.5 wt % and further reacted for 30 min.…”

“…On the other hand, a topographical cue is naturally fulfilled by the physical presence of adsorbed particles on the substrate. In this study, a colloidal hydrogel particle system recently developed by our group was applied. , These particles were formed readily in water by “click” reaction between monomers of bisepoxide and polyetheramine. Because of the presence of amine groups, the particles are cationic in nature under physiological pH.…”

Application of Acrolein Imines to Organic Synthesis, Biofunctional Studies, and Clinical Practice

“…Acrolein released in large quantities from disordered cells mediates a sequential [4+4] imino‐polymerization reaction with polyamines to yield a diazacyclooctane hydrogel. This highly cationic and conformationally flexible hydrogel can induce cell death when it adheres firmly to negatively charged cell surfaces [16a,20] …”