Thermoresponsive zwitterionic poly(phosphobetaine) microgels: Effect of macro-RAFT chain length and cross-linker molecular weight on their antifouling properties

Adsorption of proteins on biological surfaces is a detrimental phenomenon that reduces the work-life of the implants in various biomedical applications. Here, we synthesized a new class of thermoresponsive zwitterionic poly(phosphobetaine) (PMPC) microgel with excellent surface antifouling property by macro-RAFT mediated thiol-epoxy click reaction. End-group modified zwitterionic PMPC homopolymers with well-defined molecular weight and narrow dispersity were grafted onto poly(N-vinylcaprolactam-co-glycidyl methacrylate) (PVG) copolymer backbone followed by addition of a cross-linker, leading to microgel formation. While no upper critical solution temperature (UCST) was found in poly(N-vinylcaprolactam-co-glycidyl methacrylate-g-2-methacryloyloxyethyl phosphorylcholine) (PVGP) graft copolymers, the corresponding microgels exhibited both UCST and lower critical solution temperature (LCST) transitions, related to the swelling and collapse of PMPC and poly (N-vinylcaprolactam) (PVCL) components respectively. An increase in the molecular chain length of the PMPC increased the shifting of UCST and LCST of the microgels to higher temperatures, due to the ability of zwitterionic groups to coordinate a large number of water molecules. The effect of the variation in the molecular weights of amphiphilic poly(ethylene glycol) diamine (PEG-NH2) cross-linker was also reflected in both temperature and salt responsiveness of the microgels. The efficacy of the microgels as potential antifouling materials was further studied by fluorescence microscopy and XPS analysis on microgel coatings treated with FITC-BSA solution and pure BSA solution respectively. Lower protein adsorption was observed for microgels grafted with higher molecular chain length of PMPC, whereas, the microgels synthesized using higher molecular weight PEG-NH2 diamine cross-linker displayed greater protein adsorption on their surfaces

Spectrum of diffuse parenchymal lung diseases with special reference to idiopathic pulmonary fibrosis and connective tissue disease: An eastern India experience

Objective: To evaluate the clinical spectrum of diffuse parenchymal lung diseases (DPLD) encountered in the Indian setting and to compare idiopathic pulmonary fibrosis (IPF) and connective tissue disease associated DPLD (CTD-DPLD), the two commonest aetiologies. Materials and Methods: A prospective study of clinical, imaging and laboratory parameters of patients diagnosed as DPLD and followed up in the Pulmonary Medicine Department of a tertiary-care teaching institution in eastern India was conducted over a period of one year. Results: 92 patients of DPLD were diagnosed in the study period with IPF (n = 35, 38.04%), CTD-DPLD (n = 29, 31.5%), hypersensitivity pneumonitis (n = 10, 10.9%), sarcoidosis (n = 5, 5.4%) and silicosis (n = 5, 5.4%) being the common causes. The CTD-DPLD group had a lower mean age (39.5 ± 1.86 vs 56.9 ± 1.12 years), a longer duration of symptoms (3.5 ± 0.27 vs 2.5 ± 0.26 years), more extra pulmonary manifestations, significantly more base line FVC and 6-minute-walk-distance than the IPF patients. 19 patients of IPF (54%) opted for treatment. All the IPF patients had a significant fall in FVC after six months (mean change -0.203 ± 0.01 litres) compared to the CTD-DPLD group (mean change - 0.05 ± 0.04 litres.) Conclusion: CTD-DPLD patients belong to a younger age group, with longer duration of symptoms, more extrapulmonary features, better physiological parameters and better response to therapy than IPF patients. Larger prospective epidemiological studies and enrolment in clinical trials are necessary for better understanding of the spectrum of diffuse parenchymal lung disorders and their therapeutic options

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

Thermoresponsive zwitterionic poly(phosphobetaine) microgels : Effect of macro‐RAFT chain length and cross‐linker molecular weight on their antifouling properties

Adsorption of proteins on biological surfaces is a detrimental phenomenon that reduces the work-life of the implants in various biomedical applications. Here, we synthesized a new class of thermoresponsive zwitterionic poly(phosphobetaine) (PMPC) microgel with excellent surface antifouling property by macro-RAFT mediated thiol-epoxy click reaction. End-group modified zwitterionic PMPC homopolymers with well-defined molecular weight and narrow dispersity were grafted onto poly(N-vinylcaprolactam-co-glycidyl methacrylate) (PVG) copolymer backbone followed by addition of a cross-linker, leading to microgel formation. While no upper critical solution temperature (UCST) was found in poly(N-vinylcaprolactam-co-glycidyl methacrylate-g-2-methacryloyloxyethyl phosphorylcholine) (PVGP) graft copolymers, the corresponding microgels exhibited both UCST and lower critical solution temperature (LCST) transitions, related to the swelling and collapse of PMPC and poly (N-vinylcaprolactam) (PVCL) components respectively. An increase in the molecular chain length of the PMPC increased the shifting of UCST and LCST of the microgels to higher temperatures, due to the ability of zwitterionic groups to coordinate a large number of water molecules. The effect of the variation in the molecular weights of amphiphilic poly(ethylene glycol) diamine (PEG-NH2) cross-linker was also reflected in both temperature and salt responsiveness of the microgels. The efficacy of the microgels as potential antifouling materials was further studied by fluorescence microscopy and XPS analysis on microgel coatings treated with FITC-BSA solution and pure BSA solution respectively. Lower protein adsorption was observed for microgels grafted with higher molecular chain length of PMPC, whereas, the microgels synthesized using higher molecular weight PEG-NH2 diamine cross-linker displayed greater protein adsorption on their surfaces

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

Thermoresponsive zwitterionic poly(phosphobetaine) microgels:Effect of macro-RAFT chain length and cross-linker molecular weight on their antifouling properties

Adsorption of proteins on biological surfaces is a detrimental phenomenon that reduces the work-life of the implants in various biomedical applications. Here, we synthesized a new class of thermoresponsive zwitterionic poly(phosphobetaine) (PMPC) microgel with excellent surface antifouling property by macro-RAFT mediated thiol-epoxy click reaction. End-group modified zwitterionic PMPC homopolymers with well-defined molecular weight and narrow dispersity were grafted onto poly(N-vinylcaprolactam-co-glycidyl methacrylate) (PVG) copolymer backbone followed by addition of a cross-linker, leading to microgel formation. While no upper critical solution temperature (UCST) was found in poly(N-vinylcaprolactam-co-glycidyl methacrylate-g-2-methacryloyloxyethyl phosphorylcholine) (PVGP) graft copolymers, the corresponding microgels exhibited both UCST and lower critical solution temperature (LCST) transitions, related to the swelling and collapse of PMPC and poly (N-vinylcaprolactam) (PVCL) components respectively. An increase in the molecular chain length of the PMPC increased the shifting of UCST and LCST of the microgels to higher temperatures, due to the ability of zwitterionic groups to coordinate a large number of water molecules. The effect of the variation in the molecular weights of amphiphilic poly(ethylene glycol) diamine (PEG-NH2) cross-linker was also reflected in both temperature and salt responsiveness of the microgels. The efficacy of the microgels as potential antifouling materials was further studied by fluorescence microscopy and XPS analysis on microgel coatings treated with FITC-BSA solution and pure BSA solution respectively. Lower protein adsorption was observed for microgels grafted with higher molecular chain length of PMPC, whereas, the microgels synthesized using higher molecular weight PEG-NH2 diamine cross-linker displayed greater protein adsorption on their surfaces

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

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