N-isopropylacrylamide Copolymers Research Articles

N-isopropylacrylamide and spiropyran copolymer-grafted fluorescent carbon nanoparticles with dual responses to light and temperature stimuli

The fluorescent nanocomposites of carbon nanoparticles grafted with N-isopropylacrylamide and spiropyran copolymers (f-CNP-g-poly(NIPAM-co-SP)) were successfully synthesized via reversible addition-fragmentation chain transfer polymerization. The synthesized f-CNP-g-poly(NIPAM-co-SP) nanocomposites could be well dissolved in water and retain the fluorescence of carbon nanoparticles, which could simultaneously fluoresce blue-green and red. The blue-green and red fluorescence of the f-CNP-g-poly(NIPAM-co-SP) nanocomposites dissolved in water could be reversibly switched under UV and visible light stimuli. When the temperature increased from room temperature (20 °C) to 38 °C, the blue-green fluorescence intensity decreased, the red fluorescence intensity increased, and the average hydrodynamic diameter of the f-CNP-g-poly(NIPAM-co-SP) nanocomposites increased due to aggregation. The fluorescent carbon nanoparticles were grafted with the copolymers of N-isopropylacrylamide and spiropyran (f-CNP-g-poly(NIPAM-co-SP)), which have dual responses to light and temperature stimuli when they are in an aqueous solution. The blue-green and red fluorescence of the f-CNP-g-poly(NIPAM-co-SP) nanocomposites dissolved in water could be reversibly switched under UV and visible light stimuli. Meanwhile, when the temperature increased from room temperature (20 °C) to 38 °C, the blue-green fluorescence intensity decreased, the red fluorescence intensity increased, and the average hydrodynamic diameter of the f-CNP-g-poly(NIPAM-co-SP) nanocomposites increased due to aggregation.

Naphthalimide‐Based Aggregation‐Induced Emissive Polymeric Hydrogels for Fluorescent Pattern Switch and Biomimetic Actuators

Front Cover: In article 2000123, Wei Lu, Tao Chen and co-workers prepare a robust aggregation-induced emissive polymeric hydrogel by copolymerization of N-isopropylacrylamide and a specially designed 4-phenoxy-N-allyl-1,8-naphthalimide (PhAN) monomer. The hydrogel is characterized with thermally controlled emission/transmittance response, and its potential applications as a fluorescence pattern switch and biomimetic actuator are demonstrated.

The Influence of Vanillin Acrylate Derivative on the Phase Separation Temperature of Environmental Photo-Cross-Linked N-isopropylacrylamide Copolymer and Hydrogel Thin Films

The present study emphasizes the fabrication of thermal and pH-responsive photo-cross-linked polymers and hydrogel thin films. N-isopropylacrylamide was used as a thermal responsive monomer, while a new pH-responsive monomer was synthesized based on vanillin 2-((dimethylamino)methyl)-4-formyl-6-methoxyphenyl acrylate (DMAMVA). The photo-cross-linker (DMIA) and adhesion promotor (DMITAAc) have been prepared. All compounds were investigated by 1H NMR, 13C NMR, and FTIR. Terpolymers of 10, 15, and 20 mol% DMAMVA and 10 mol% of DMIA with N-isopropylacrylamide were fabricated. The chemical structures were investigated, and the molecular weights were determined by gel permeation chromatography GPC. Moreover, the glass transition temperatures were also recorded by differential scanning calorimeter DSC. The lower critical solution temperatures of polymers were determined by turbidity tests using UV–Vis spectroscopy. The polymer solution of 20 mol% sample was spin-coated over the gold to form hydrogel thin film within photo-cross-linking by the UV lamp. The film thickness was determined by the SPR-OW technique using Kretschmann configuration. The swelling was recorded and the transition temperature of hydrogel was determined as the change in volume degree of swelling and refractive index with the change in temperature. The dual responsive functional photo-cross-linked polymers and hydrogel thin films have significant importance in the grafting of some biological molecules.

Copolymeric nano/microgels of N-isopropylacrylamide and carboxyalkyl methacrylamides: Effect of methylene chains and the ionization state of the weak acids on size and sensitivity to pH and temperature

ABSTRACT We prepared nano/microgels by precipitation copolymerization of N-isopropylacrylamide (NIPAAm), and one of three different carboxyalkyl methacrylamides [methacryloylamido hexanoic acid (M5), 8-methacryloylamido octanoic acid (M7), and 11-methacryloylamido undecanoic acid (M10)], either in the acid forms or as carboxylates (potassium salts). The hydrodynamic diameter (Dh) of the nano/microgels prepared with the carboxylates was smaller (≈100 nm for M10 copolymers), compared to the size of homopolymeric NIPAAm microgels prepared by dispersion polymerization (around 600 nm), indicating that the carboxylates act as surfactants reducing the size of the seeds during the polymerization process. These materials presented a swollen-shrunken transition temperature (T tr) similar to the T tr of the homopolymeric NIPAAm microgels, without pH sensitivity. On the other hand, the copolymeric microgels prepared from the acid form of the comonomers have a similar or bigger size than NIPAAm microgels. For these copolymers, the T tr can be tuned by the type and proportion of acid comonomer used and present pH sensitivity. This is important for biomedical applications such as positive temperature control release. Polyelectrolyte titration demonstrates that the nano/microgels prepared with the carboxylates behave as hard spheres, while the microgels prepared with the weak acid behave as porous materials.

Highly Branched Waxy Potato Starch-Based Polyelectrolyte: Controlled Synthesis and the Influence of Chain Composition on Solution Rheology

In the present work, a series of highly branched random copolymers of acrylamide (AM), sodium 2-acrylamido-2-methyl-1-propanesulfonate (SAMPS), and N-isopropylacrylamide (NIPAM) were prepared by using water-soluble waxy potato starch-based macroinitiator via aqueous Cu0-mediated living radical polymerization (25 °C). The AM/SAMPS/NIPAM ratio was varied to investigate the influence of chain composition on the aqueous rheological properties of the prepared copolymers. Rheological results indicated an optimum SAMPS intake (25 mol %) for the balanced performance of viscosity and salt resistance in saline water. The intake of NIPAM units (e.g., 25 mol %), contrary to what was expected, undermines the thickening ability of the copolymers in saline water because of hydrophobic association. In high salinity solution, thermo-thickening behavior can be observed at low shear rates (γ ≤ 3 s–1) because of the screening effect of salt on the negatively charged SAMPS units. At the high shear rate, the thermo-thickening behavior disappears because of the disruption of the NIPAM aggregates. These results pave the way toward the use of the prepared polymers as rheology modifiers in a variety of possible formulations for different applications, in particular in enhanced oil recovery.

Tough, self-healable and conductive elastomers based on freezing-thawing strategy

Flexible conductive elastomers with excellent mechanical properties and body-temperature self-healing are highly desirable for wearable electronics. However, it is still a challenge to develop such elastomers because mechanical strength and healing efficiency are contradictory and are difficult to realize the concurrent optimization. Herein, we design stretchable conductive composites by combining tough self-healable elastomeric matrix and in-situ formed polypyrrole network. The elastomeric matrix, fabricated by copolymerization of N-isopropylacrylamide and 2-methoxyethylacrylate, displays superior mechanical strength (8.2 MPa) and high body-temperature healing efficiency (94%), enabled by combination of the dynamic hydrogen bonding and microphase separation structures from freezing-thawing treatment. The resultant conductive elastomers exhibit excellent strength of 7.4 MPa, high stretchability of 410%, good electrical conductivity of 12.5 S/m and over 70% body-temperature healing efficiency. Moreover, it is revealed that the conductive elastomers could be used as strain sensors due to high sensitivity of stretchability. The tough self-healing conductive elastomers may find potential applications in stretchable electronics and soft robotics

Modification of cellulose nanocrystal with dual temperature- and CO2-responsive block copolymers for ion adsorption applications

Cellulose nanocrystal (CNC)-grafted smart polymers have potential applications as adsorbents by providing simple regeneration process. In this study, carbon dioxide (CO2)- and temperature-responsive free block copolymers of N-isopropylacrylamide and (2-dimethylaminoethyl) methacrylate with different block lengths were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization. In addition, CNC was modified with the similar block copolymers by surface-initiated RAFT method. The synthesized block copolymers were used in nitrate ion removal from aqueous solutions. The synthesis process was confirmed by Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance (1H NMR) analysis, thermal gravimetric analysis, scanning electron microscopy, and transmission electron microscopy. Stimuli-responsivity of the free polymers was studied by pH measurement, turbidity investigation, and dynamic light scattering analysis. CO2-responsivity of the block copolymers in aqueous solution was confirmed by reduction of pH in the presence of CO2 by protonation of the PDMAEMA blocks. The copolymers with higher length of PDMAEMA showed highly intense CO2-responsivity. Deprotonation of the PDMAEMA units by purging N2 represents reversible responsivity of the copolymers. Turbidity analysis showed different critical solution temperatures (CST) for the block copolymers with various block lengths. Two different micellar and vesicular morphologies were observed for the self-assembled copolymers at temperatures above and below CST of the copolymers, which is related to the hydrophobic/hydrophilic block ratio. CO2-switched nitrate ion adsorption from aqueous solution at two temperatures (37 and 60 °C) was studied by UV–vis spectroscopy using the synthesized products as adsorbent. Adsorption of nitrate ions from aqueous solutions was increased by protonation of the PDMAEMA segments upon CO2 purging. Presence of CNC, morphology of the self-assembled copolymers, temperature, and time of CO2 purging affect the nitrite ion adsorption capacity. The maximum adsorption capacity (420 mg/g) is related to the sample with vesicular assemblies in aqueous solution and higher PDMAEMA block length at temperatures below CST of the block copolymer. N2 purging resulted in deprotonation of the PDMAEMA blocks and regeneration of the samples. Finally, the CNC substrate can be used in regeneration of the samples with simple filtration process in addition to the stimuli-regeneration process.

Swellable Copolymers of N-isopropylacrylamide and Alkyl Acrylic Acids for Optical pH Sensing.

Swellable polymers that respond to pH (including a portion of the physiological pH range) have been prepared from N-isopropylacrylamide (NIPA) copolymerized with acrylic acid, methacrylic acid, ethacrylic acid or propacrylic acid by dispersion polymerization. When the swellable polymer particles are dispersed in a polyvinyl alcohol (PVA) hydrogel membrane, large changes occur in the turbidity of the membrane (which is measured using an absorbance spectrometer) as the pH of the buffer solution in contact with the hydrogel membrane is varied. The swelling of the NIPA copolymer is nonionic, as the ionic strength of the buffer solution in contact with the PVA membrane was increased from 0.1 to 1.0 M without a decrease in the swelling. For many of these NIPA copolymers, swelling was also reversible in both low- and high ionic strength pH-buffered media and at ambient and physiological temperatures. The composition of the formulation used to prepare these copolymers of NIPA can be correlated to the enthalpy and entropy of the pH-induced swelling.

Core\u2013shell polymeric nanoparticles co-loaded with photosensitizer and organic dye for photodynamic therapy guided by fluorescence imaging in near and short-wave infrared spectral regions

BackgroundBiodistribution of photosensitizer (PS) in photodynamic therapy (PDT) can be assessed by fluorescence imaging that visualizes the accumulation of PS in malignant tissue prior to PDT. At the same time, excitation of the PS during an assessment of its biodistribution results in premature photobleaching and can cause toxicity to healthy tissues. Combination of PS with a separate fluorescent moiety, which can be excited apart from PS activation, provides a possibility for fluorescence imaging (FI) guided delivery of PS to cancer site, followed by PDT.ResultsIn this work, we report nanoformulations (NFs) of core–shell polymeric nanoparticles (NPs) co-loaded with PS [2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a, HPPH] and near infrared fluorescent organic dyes (NIRFDs) that can be excited in the first or second near-infrared windows of tissue optical transparency (NIR-I, ~ 700–950 nm and NIR-II, ~ 1000–1350 nm), where HPPH does not absorb and emit. After addition to nanoparticle suspensions, PS and NIRFDs are entrapped by the nanoparticle shell of co-polymer of N-isopropylacrylamide and acrylamide [poly(NIPAM-co-AA)], while do not bind with the polystyrene (polySt) core alone. Loading of the NIRFD and PS to the NPs shell precludes aggregation of these hydrophobic molecules in water, preventing fluorescence quenching and reduction of singlet oxygen generation. Moreover, shift of the absorption of NIRFD to longer wavelengths was found to strongly reduce an efficiency of the electronic excitation energy transfer between PS and NIRFD, increasing the efficacy of PDT with PS-NIRFD combination. As a result, use of the NFs of PS and NIR-II NIRFD enables fluorescence imaging guided PDT, as it was shown by confocal microscopy and PDT of the cancer cells in vitro. In vivo studies with subcutaneously tumored mice demonstrated a possibility to image biodistribution of tumor targeted NFs both using HPPH fluorescence with conventional imaging camera sensitive in visible and NIR-I ranges (~ 400–750 nm) and imaging camera for short-wave infrared (SWIR) region (~ 1000–1700 nm), which was recently shown to be beneficial for in vivo optical imaging.ConclusionsA combination of PS with fluorescence in visible and NIR-I spectral ranges and, NIR-II fluorescent dye allowed us to obtain PS nanoformulation promising for see-and-treat PDT guided with visible-NIR-SWIR fluorescence imaging.

Thermoresponsive chiral stationary phase functionalized with the copolymer of β-cyclodextrin and N-isopropylacrylamide for high performance liquid chromatography

A novel chiral stationary phase (CSP) was prepared through the reaction of surface-initiated atom transfer radical polymerization (ATRP) by the copolymerization of thermoresponsive N-isopropylacrylamide (NIPAM) and β-cyclodextrin (β-CD) on the silica beads for high performance liquid chromatography (HPLC). X-ray photoelectron spectroscopy (XPS), elemental analysis (EA), Fourier transform infrared spectrometry (FT-IR), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM) were applied to characterize the surface property of modified silica. Thermoresponsive modulation for the effect on enantioselectivity were investigated with chiral reagents including 1-phenyl-1-propanol, styrene oxide, 2-phenylpropionic acid and commercial chiral drugs comprising ibuprofen and labetalol hydrochloride. The column efficiency was evaluated by chromatographic parameters including retention factor (k), selective factor (α), resolution (Rs), plate number (N) and peak tailing factor (Tf). The results showed that five chiral solutes could be separated on the prepared smart column. And the selectivity of these compounds could be modulated by regulating the column temperature. It was contributed to the thermoresponsive NIPAM assisting β-CD to separate these chiral compounds. These results indicated that the thermoresponsive CSP would be a potential tool for separation of hydrophilic and hydrophobic chiral drugs and this paper provided a novel method for chiral separation in the future.

Conversion of an Injectable MMP-Degradable Hydrogel into Core-Cross-Linked Micelles.

In this study, a new type of injectable hydrogel called “HyMic” that can convert into core cross-linked (CCL) micelles upon exposure to matrix metalloproteinases (MMP’s), was designed and developed for drug delivery applications. HyMic is composed of CCL micelles connected via an enzyme cleavable linker. To this end, two complementary ABA block copolymers with polyethylene glycol (PEG) as B block were synthesized using atom transfer radical polymerization (ATRP). The A blocks were composed of a random copolymer of N-isopropylacrylamide (NIPAM) and either N-(2-hydroxypropyl)methacrylamide-cysteine (HPMA-Cys) or N-(2-hydroxypropyl) methacrylamide-ethylthioglycolate succinic acid (HPMA-ETSA). Mixing the aqueous solutions of the obtained polymers and rising the temperature above the cloud point of the PNIPAM block resulted in the self-assembly of these polymers into flower-like micelles composed of a hydrophilic PEG shell and hydrophobic core. The micellar core was cross-linked by native chemical ligation between the cysteine (in HPMA-Cys) and thioester (in HPMA-ETSA) functionalities. A slight excess of thioester to cysteine groups (molar ratio 3:2) was used to allow further chemical reactions exploiting the unreacted thioester groups. The obtained micelles displayed a Z-average diameter of 80 ± 1 nm (PDI 0.1), and ζ-potential of −4.2 ± 0.4 mV and were linked using two types of pentablock copolymers of P(NIPAM-co-HPMA-Cys)-PEG-peptide-PEG-P(NIPAM-co-HPMA-Cys) (Pep-NC) to yield hydrogels. The pentablock copolymers were synthesized using a PEG-peptide-PEG ATRP macroinitiator and the peptide midblock (lysine-glycine-proline-glutamine-isoleucine-phenylalanine-glycine-glutamine-lysine (Lys-Gly-Pro-Gln-Gly-Ile-Phe-Gly-Gln-Lys)) consisted of either l- or d-amino acids (l-Pep-NC or d-Pep-NC), of which the l-amino acid sequence is a substrate for matrix metalloproteases 2 and 9 (MMPs 2 and 9). Upon mixing of the CCL micelles and the linker (l/d-Pep-NC), the cysteine functionalities of the l/d-Pep-NC reacted with remaining thioester moieties in the micellar core via native chemical ligation yielding a hydrogel within 160 min as demonstrated by rheological measurements. As anticipated, the gel cross-linked with l-Pep-NC was degraded in 7–45 days upon exposure to metalloproteases in a concentration-dependent manner, while the gel cross-linked with the d-Pep-NC remained intact even after 2 months. Dynamic light scattering analysis of the release medium revealed the presence of nanoparticles with a Z-average diameter of ∼120 nm (PDI < 0.3) and ζ-potential of ∼−3 mV, indicating release of core cross-linked micelles upon HyMic exposure to metalloproteases. An in vitro study demonstrated that the released CCL micelles were taken up by HeLa cells. Therefore, HyMic as an injectable and enzyme degradable hydrogel displaying controlled and on-demand release of CCL micelles has potential for intracellular drug delivery in tissues with upregulation of MMPs, for example, in cancer tissues.

High oxygen preservation hydrogels to augment cell survival under hypoxic condition

Cell therapy is a promising approach for ischemic tissue regeneration. However, high death rate of delivered cells under low oxygen condition, and poor cell retention in tissues largely limit the therapeutic efficacy. Using cell carriers with high oxygen preservation has potential to improve cell survival. To increase cell retention, cell carriers that can quickly solidify at 37 °C so as to efficiently immobilize the carriers and cells in the tissues are necessary. Yet there lacks cell carriers with these combined properties. In this work, we have developed a family of high oxygen preservation and fast gelation hydrogels based on N-isopropylacrylamide (NIPAAm) copolymers. The hydrogels were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization of NIPAAm, acrylate-oligolactide (AOLA), 2-hydroxyethyl methacrylate (HEMA), and methacrylate-poly(ethylene glycol)-perfluorooctane (MAPEGPFC). The hydrogel solutions exhibited sol-gel temperatures around room temperature and were flowable and injectable at 4°C. They can quickly solidify (≤6 s) at 37°C to form flexible gels. These hydrogels lost 9.4~29.4% of their mass after incubation in Dulbecco's Phosphate-Buffered Saline (DPBS) for 4 weeks. The hydrogels exhibited a greater oxygen partial pressure than DPBS after being transferred from a 21% O2 condition to a 1% O2 condition. When bone marrow mesenchymal stem cells (MSCs) were encapsulated in the hydrogels and cultured under 1% O2, the cells survived and proliferated during the 14-day culture period. In contrast, the cells experienced extensive death in the control hydrogel that had low oxygen preservation capability. The hydrogels possessed excellent biocompatibility. The final degradation products did not provoke cell death even when the concentration was as high as 15 mg/ml, and the hydrogel implantation did not induce substantial inflammation. These hydrogels are promising as cell carriers for cell transplantation into ischemic tissues. Statement of SignificanceStem cell therapy for ischemic tissues experiences low therapeutic efficacy largely due to poor cell survival under low oxygen condition. Using cell carriers with high oxygen preservation capability has potential to improve cell survival. In this work, we have developed a family of hydrogels with this property. These hydrogels promoted the encapsulated stem cell survival and growth under low oxygen condition.

Use of Nanotrap particles for the capture and enrichment of Zika, chikungunya and dengue viruses in urine.

Nanotrap® (NT) particles are hydrogel microspheres developed for target analyte separation and discovery applications. NT particles consist of cross-linked N-isopropylacrylamide (NIPAm) copolymers that are functionalized with a variety of chemical affinity baits to enable broad-spectrum collection and retention of target proteins, nucleic acids, and pathogens. NT particles have been previously shown to capture and enrich arboviruses including Rift Valley fever and Venezuelan equine encephalitis viruses. Yet, there is still a need to enhance the detection ability for other re-emerging viruses such as Zika (ZIKV), chikungunya (CHIKV), and dengue (DENV) viruses. In this study, we exploited NT particles with different affinity baits, including cibacron blue, acrylic acid, and reactive red 120, to evaluate their capturing and enrichment capability for ZIKV, DENV and CHIKV in human fluids. Our results demonstrate that CN1030, a NT particle conjugated with reactive red 120, can recover between 8-16-fold greater genomic copies of ZIKV, CHIKV and DENV in virus spiked urine samples via RT-qPCR, superior to the other chemical baits. Also, we observed that CN1030 simultaneously enriched ZIKV, CHIKV and DENV in co-infection-based settings and could stabilize ZIKV, but not CHIKV infectivity in saliva spiked samples. CN1030 enriched viral detection at various viral concentrations, with significant enhancement observed at viral titers as low as 100 PFU/mL for ZIKV and 10 PFU/mL for CHIKV. The detection of ZIKV was further enhanced with NT particles by processing of larger volume urine samples. Furthermore, we developed a magnetic NT particle, CN3080, based on the same backbone of CN1030, and demonstrated that CN3080 could also capture and enrich ZIKV and CHIKV in a dose-dependent manner. Finally, in silico docking predictions support that the affinity between reactive red 120 and ZIKV or CHIKV envelope proteins appeared to be greater than acrylic acid. Overall, our data show that NT particles along with reactive red 120 can be utilized as a pre-processing technology for enhancement of detecting febrile-illness causing viruses.

Responsive Adsorption of N-Isopropylacrylamide Based Copolymers on Polymer Brushes.

We investigate the adsorption of pH- or temperature-responsive polymer systems by ellipsometry and neutron reflectivity. To this end, temperature-responsive poly (N-isopropylacrylamide) (PNIPAM) brushes and pH-responsive poly (acrylic acid) (PAA) brushes have been prepared using the “grafting onto” method to investigate the adsorption process of polymers and its reversibility under controlled environment. To that purpose, macromolecular brushes were designed with various chain lengths and a wide range of grafting density. Below the transition temperature (LCST), the characterization of PNIPAM brushes by neutron reflectivity shows that the swelling behavior of brushes is in good agreement with the scaling models before they collapse above the LCST. The reversible adsorption on PNIPAM brushes was carried out with linear copolymers of N-isopropylacrylamide and acrylic acid, P(NIPAM-co-AA). While these copolymers remain fully soluble in water over the whole range of temperature investigated, a quantitative adsorption driven by solvophobic interactions was shown to proceed only above the LCST of the brush and to be totally reversible upon cooling. Similarly, the pH-responsive adsorption driven by electrostatic interactions on PAA brushes was studied with copolymers of NIPAM and N,N-dimethylaminopropylmethacrylamide, P(NIPAM-co-MADAP). In this case, the adsorption of weak polycations was shown to increase with the ionization of the PAA brush with interactions mainly located in the upper part of the brush at pH 7 and more deeply adsorbed within the brush at pH 9.

Collapse–Decollapse of Thermosensitive Polyelectrolyte Gels in Aqueous Media

The effect of temperature on water sorption by gels based on the copolymers of N-isopropylacrylamide with sodium p-styrene sulfonate containing 1, 3, and 5 mol % of charged monomer units is studied in aqueous media in the presence of salt (NaCl, KCl) or urea. It is shown that the incubation of gels in salt solutions leads to compression of the gels. With increasing temperature, the collapse of gels is observed in all studied media. The difference in the gel collapse temperature in water and salt solution increases with an increase in the fraction of charged units in the polymer gel network and in the salt concentration in the solution. With a return temperature decrease and gel decollapse, the mass of all gels in salt solutions (0.5–5.0 wt %) is completely restored. The incubation of gels in aqueous solutions of urea (0.5–5.0 wt %) has practically no effect on water sorption by gels before the collapse and the collapse temperature. However, the degree of swelling of polyelectrolyte gels during decollapse caused by a temperature decrease is much lower than the initial value, in contrast to the completely reversible swelling of the poly(N-isopropylacrylamide) gel under similar conditions.

Thermo-Sensitivity of poly-N-isopropylacrylamide with Statistically Introduced D,L-Allylglycine Betainic Units

Statistical copolymers of N-isopropylacrylamide containing 2.2 – 2.7 mol % D,L-allylglycine were synthesized. The sample with 2.2 mol % allylglycine and molar mass 320000 g/mol was studied using light scattering and turbidimetry while heated in water and water–salt solutions. Temperature dependencies of light scattering intensity and optical transmission as well as hydrodynamic size and composition of the scattering entities were obtained in a wide range of pH. The onset temperatures of phase separation were independent of pH; however, in the basic pH region the phase transition was widened as compared to the neutral and acid media. It was shown that a small content of allylglycine results in a different thermoresponsive behavior of the copolymer as compared with N-isopropylacrylamide homopolymer. The addition of a physiological amount of NaCl shifts the copolymer thermo-sensitivity toward lower temperatures.

Osteogenic scaffolds based on fumaric/N-isopropylacrylamide copolymers: Designed, properties and biocompatibility studies

In the present work the creation of a new biomaterial aimed at bone tissue regeneration is shown, covering the synthesis of the polymers, the material design and their exhaustive physicochemical and biological characterization. The copolymers of dioctyl fumarate (DOF) and N-isopropylacrylamide (NIPAM) were synthetized and characterized by size exclusion chromatography, 1H NMR and its thermal properties were studied by DSC and TGA analyses. Based on their properties, two copolymers with different DOF content were selected as raw material to design scaffolds for bone tissue regeneration. The scaffolds were prepared by casting and electrospinning technique, giving rise to biomaterials with particular chemical and topographic surface which were characterized by water contact angle and scanning electron microscopy (SEM) analysis. The cytotoxicity and biodegradation by murine macrophage RAW 264.7 cells was assay, while biocompatibility and osteogenic induction were made using bone marrow progenitor cells (BMPC). None of the biomaterials obtained showed cytotoxicity. The biological properties suggest that the cells adhere and proliferate better on biomaterials with higher DOF content and fibrous morphology. All scaffolds support osteoblastic cell differentiation, but to a greater extent on the biomaterial that has higher DOF content prepared by casting. Altogether, our results suggesting that these biomaterials could be useful in the bone tissue engineering.

Dispersion polymerization of n-butylacrylate under the action of acrylic acid and N-isopropylacrylamide copolymers

The regularities of dispersion radical polymerization of n-butylacrylate in water-alcohol medium under the action of polymer tritiocarbonates based on copolymers of acrylic acid and N-isopropylacrylamide have been investigated. The conditions for the formation of a block copolymer with controlled molecular weight and high yield have been found. The conditions of formation of stable suspensions of block copolymers with unimodal particle size distribution have been determined.

Synthesis and characterization of poly(N-isopropylacrylamide-co-N,N′-methylenebisacrylamide-co-acrylamide) core – Silica shell nanoparticles by using reactive surfactant polyoxyethylene alkylphenyl ether ammonium sulfate

We report a novel approach based on using polyoxyethylene alkylphenyl ether ammonium sulfate (HS10) as an anion reactive surfactant, which greatly reduced the size of poly(N-isopropylacrylamide-co-acrylamide-co-N,N′-methylenebisacrylamide) [P(NIPAM/AM/MBA)] microgel core – silica shell particles. First, the microgel cores were synthesized by copolymerization of N-isopropylacrylamide (NIPAM), N,N′-methylenebisacrylamide (MBA) with a variation of acrylamide (AM) and HS10 concentration in water. It followed by silica encapsulation of the microgel cores via the addition of 3-glycidyloxypropyltrimethoxysilane (GLYMO) and tetraethyl orthosilicate (TEOS) at alkaline environment (pH 12). It is interesting to note that the size of both PNIPAM-based microgel cores and PNIPAM-based microgel core – silica shell particles were well-controlled by using a small level of HS10. Furthermore, SEM images of the hybrid core – shell particles show the well-defined spherical morphology with monodisperse particle size distribution. As expected, HS10-containing samples are covered by the porous silica shell layer, instead of continuous silica shell obtained from HS10-free samples observed in TEM images. This novel incorporation not only well controls the core size and shell morphology, leading to increase their specific surface area but also does not greatly affect the thermo-sensitivity of final products. The resultant thermo-responsive microgel core – silica shell particles with controlled particle morphology and physicochemical properties are useful for biomedical application fields.

Azlactone-functionalized smart block copolymers for organocatalyst immobilization

Nucleophilic ring-opening reaction of azlactone moieties was used for the immobilization of organocatalysts on smart block copolymers. Copolymerization of N-isopropylacrylamide with 2-vinyl-4,4-dimethylazlactone using a PEG-based macro-RAFT agent afforded temperature-sensitive block copolymers bearing azlactone side groups. Three different organocatalysts possessing primary amino groups were synthesized on the basis of L-proline and L-prolineamide using standard peptide coupling procedures. Organocatalyst immobilization was achieved using a post-polymerization reaction of the primary amino group with the azlactone moiety. The organocatalyst-functionalized block copolymers exhibited a temperature induced self-aggregation upon exceeding a critical phase transition temperature. The block copolymer aggregates with the immobilized organocatalyst in the core were subjected to the aldol reaction of cyclohexanone and p-nitrobenzaldehyde in water. Good diastereo- and enantioselectivities were observed, particularly for the immobilized prolineamides. Organocatalyst separation and reusability was demonstrated for five reaction cycles with no loss in catalyst reactivity. Finally, the applicability of the immobilized organocatalyst to the aldol reaction of cyclohexanone with differently substituted benzaldehydes in water was shown.