Stimuli‐Responsive Hydrogels Synthesis using Free Radical and RAFT Polymerization

Abstract

Summary: Temperature and pH stimuli-responsive hydrogel particles were synthesized using inverse-suspension polymerization in batch stirred reactor. Different water soluble co-monomers were present in the initial mixture (e.g. N-isopropylacrylamide and acrylic acid) as well as crosslinkers with different functionalities. Different operating conditions such as polymerization temperature, monomers dilution, neutralization and the initial ratios of co-monomers and monomers/crosslinker were also tried. Hydrogel particles were produced considering classical free-radical polymerization (FRP) and also RAFT polymerization. Commercially available RAFT agents 4-cyano-4-phenylcarbonothioylthio-pentanoic acid (CPA), 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT) and cyanomethyl dodecyl trithiocarbonate (CDT) were alternatively used. Sampling at different polymerization times allowed the study of the kinetics of polymerization through the analysis by SEC of the soluble phase. A tetra-detector array with simultaneous detection of refractive index, light scattering, intrinsic viscosity and ultra-violet signals was used in these studies. Usefulness of in-line FTIR-ATR monitoring to study the building process of such networks was also assessed. The performance of hydrogel beads was studied through drug delivery tests triggered by changes in the environmental temperature and pH. This research aims to contribute for the elucidation of the connection between the synthesis conditions, molecular architecture and properties/performance of such advanced materials.

Comparison of Thermoresponsive Hydrogels Synthesized by Conventional Free Radical and RAFT Polymerization

“…To be noted, the SR of G1R could be not evaluated because of the lack of gel consistency; we believe that this constitutes indirect evidence that non-defined chemical entanglement from side reactions (i.e., chain-chain crosslinking) contribute to the formation of gels by FRP; this explains the inability of RAFT to form gels at lower crosslinker feeds, simply because the reaction mechanism is more well-defined with a minimization of side-reactions [34] leading to better defined crosslinks overall and this is also corroborated by the difference between the SR of FRP and RAFT gels. RAFT polymerization allows for the incorporation of chemical crosslinks in a highly controlled manner, hence forming a well-defined hydrogel network [21,22,23,24,25,26]. Finally, after 24 h, the temperature was increased to 37 °C, and the SR of each gel instantly dropped to 1 due to the loss of PNIPAAm solubility in water above 32 °C.…”

“…More particularly, RAFT polymerization [18,19,20] has been used to copolymerize (di-)vinyl monomers to form more homogeneous and structurally well-defined three-dimensional (3D) networks that are difficult, if not impossible, to obtain via the conventional FRP route [19,21]; these networks find numerous applications as swelling matrices, cell/drug encapsulants, separation technologies, self-healing materials, and responsive sensors and actuators. Recently, several groups reported on the macroscopic differences between RAFT and FRP-made polymer networks [21,22,23,24,25,26]; it is generally accepted that FRP networks tend to produce less well-defined polymer meshes with collapsed micro-domains, which in turn compromise the (de-)swelling or responsive properties of the bulk materials macroscopically. Conversely, RAFT produced gels with narrow polymer mesh distributions with very good control on the polymerization kinetics.…”

Molecular imprinting in hydrogels using reversible addition-fragmentation chain transfer polymerization and continuous flow micro-reactor

“…The introduction of a RAFT agent is currently used by many researchers mainly to obtain a homogeneous polymer network by avoiding the presence of broad distributions of sizes for any sub‐structures like sub‐chains or loops. One could rationally design a close to ideal polymer network architecture by using RAFT agent.…”

“…However, microfluidic devices have their own technical challenges concerning the choice of an optimum residence time, fast enough reaction kinetics, agglomeration of particles and controlling the shape and size of the final product. Controlled radical polymerization (CRP) using a RAFT (reversible addition‐fragmentation chain transfer) agent has been considered by several researchers to improve the molecular architectures of the resulting materials (aiming at achieving lower chain heterogeneity, controlled topologies, etc.) and to control the polymerization kinetics.…”

PNIPAM-MAPOSS Hybrid Hydrogels with Excellent Swelling Behavior and Enhanced Mechanical Performance: Preparation and Drug Release of 5-Fluorouracil

“…During the drug delivery, PNIPAM hydrogels swell and load the drug at a temperature below LCST, and shrink and release the loaded drug when the temperature rises above LCST. Typical types of polymerization are free radical polymerization and reversible addition-fragmentation chain transfer polymerization (RAFT).Polymerization methods include solution polymerization, inverse microemulsion polymerization [ 14 ], inverse suspension polymerization [ 15 ], precipitation polymerization [ 16 ], etc.…”