Stimuli-Responsive Block Copolymer Micelles Based on Mussel-Inspired Metal-Coordinated Supramolecular Networks.

Amphiphilic diblock copolymers containing dopamine and zwitterions are synthesized via the RAFT polymerization method, which undergo temperature-mediated micellization in aqueous media. The presence of catechol moiety in dopamine is exploited to form pH-responsive cross-links with ferric ions (Fe3+ ) at different pH value. Herein, a comprehensive study of the effect of pH as well as temperature on the size and solution behavior of these cross-linked micelles is presented. These micelles cross-linked via metal-catechol coordination bonds can have several important biomedical applications such as degradable scaffolds for payload delivery.

Zwitterionic Nanogels and Microgels: An Overview on Their Synthesis and Applications.

Zwitterionic polymers by virtue of their unique chemical and physical attributes have attracted researchers in recent years. The simultaneous presence of positive and negative charges in the same repeat unit renders them of various interesting properties such as superhydrophilicity, which has significantly broadened their scope for being used in different applications. Among polyzwitterions of different architectures, micro- and/or nano-gels have started receiving attention only until recently. These 3D cross-linked colloidal structures show peculiar characteristics in context to their solution properties, which are attributable either to the comonomers present or the presence of different electrolytes and biological specimens. In this review, a concise yet detailed account is provided of the different synthetic techniques and application domains of zwitterion-based micro- and/or nanogels that have been explored in recent years. Here, the focus is kept solely on the "polybetaines," which have garnered maximum research interest and remain the extensively studied polyzwitterions in literature. While their vast application potential in the biomedical sector is being detailed here, some other areas of scope such as using them as microreactors for the synthesis of metal nanoparticles or making smart membranes for water-treatment are discussed in this minireview as well.

A dual thermoresponsive and antifouling zwitterionic microgel with pH triggered fluorescent "on-off" core.

A unique, tailor-made, zwitterionic, dual thermoresponsive and fluorescent microgel probe was synthesized via Reversible Addition Fragmentation chain-Transfer (RAFT) polymerization. Microgels were prepared via oil in water (o/w) emulsion polymerization where poly(carboxybetaine) (PCB) acted as a macro-RAFT reagent as well as an emulsifier. The presence of poly(N-vinylcaprolactam) (PNVCL) in the microgel system imparts the thermoresponsiveness to the system and the presence of a rhodamine derivative as fluorophore makes it responsive to pH change of the system by showing a fluorescence emission at 580 nm (reddish orange color). The dual thermoresponsiveness [i.e. the presence of upper critical solution temperature (UCST @ 12 °C) as well as lower critical solution temperature (LCST @ 33 °C)] of the microgels was studied via UV-visible spectroscopy (UV-vis) and temperature responsive dynamic light scattering (DLS) analyses. Presence of the PCB in the corona-crosslinked microgel, played a vital role in the formation of self-assembled structure as well as in protein immobilization (antifouling activity). Antifouling property was studied using UV-vis spectroscopy where bovine serum albumin (BSA) was taken as a model protein. The presence of the pH-responsive fluorescence, thermoresponsiveness as well as antifouling properties makes this zwitterionic microgel system a potential a potential candidate for medical diagnostics and for drug delivery vehicles.

Stimuli-Responsive Zwitterionic Core-Shell Microgels for Antifouling Surface Coatings.

Fouling on filtration membranes is induced by the nonspecific interactions between the membrane surface and the foulants, and effectively hinders their efficient use in various applications. Here, we established a facile method for the coating of membrane surface with a dual stimuli-responsive antifouling microgel system enriched with a high polyzwitterion content. Different poly(sulfobetaine) (PSB) zwitterionic polymers with defined molecular weights and narrow dispersities were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization and integrated onto poly(N-vinylcaprolactam) (PVCL) microgels via a controlled dosage of a cross-linker, adapting a precipitation polymerization technique to obtain a core-shell microstructure. Increasing the PSB macro-RAFT concentration resulted in a shift of both upper critical solution temperature and lower critical solution temperature toward higher temperatures. Cryogenic transmission electron microscopy at different temperatures suggested the formation of a core-shell morphology with a PVCL-rich core and a PSB-rich shell. On the other hand, the significant variations of different characteristic proton signals and reversible phase transitions of the microgel constituents were confirmed by temperature-dependent 1H NMR studies. Utilizing a quartz crystal microbalance with dissipation monitoring, we have been able to observe and quantitatively describe the antipolyelectrolyte behavior of the zwitterionic microgels. The oscillation frequency of the sensor proved to change reversibly according to the variations of the NaCl concentration, showing, in fact, the effect of the interaction between the salt and the opposite charges present in the microgel deposited on the sensor. Poly(ethersulfone) membranes, chosen as the model surface, when functionalized with zwitterionic microgel coatings, displayed protein-repelling property, stimulated by different transition temperatures, and showed even better performances at increasing NaCl concentration. These kinds of stimuli-responsive zwitterionic microgel can act as temperature-triggered drug delivery systems and as potential coating materials to prevent bioadhesion and biofouling as well.

Dual-Temperature-Responsive Microgels from a Zwitterionic Functional Graft Copolymer with Superior Protein Repelling Property.

In this work, we developed a synthetic strategy to synthesize dual-temperature-responsive low surface fouling zwitterionic microgels. Statistical poly(N-vinylcaprolactam-co-glycidyl methacrylate) copolymers were synthesized by RAFT polymerization and post-modified by thiol-epoxy click reaction with thiol end-group-modified poly(sulfobetaine) macro-RAFT (PSB-SH) to obtain poly(N-vinylcaprolactam-co-glycidyl methacrylate)-graft-poly(sulfobetaine) (PVCL-co-PGMA-g-PSB) graft copolymers. Synthesized graft copolymers were cross-linked by diamine cross-linker in water-in-oil (w/o) inverse mini-emulsion to obtain zwitterionic microgels. Using this approach, we synthesized microgels with unique microstructure, high loading and uniform distribution of poly(sulfobetaine) chains, which exhibits tunable dual-volume phase transition temperatures. The microgels also showed excellent antifouling property reflected in strongly reduced protein absorption on a microgel-coated surface observed in real time by a Quartz Crystal Microbalance with Dissipation (QCM-D) monitoring experiment with continuous flow of protein solution. Therefore, this kind of zwitterionic microgel can be potentially used for temperature-triggered drug delivery and anti-bioadhesion coating material as well.