N-isopropylacrylamide Copolymers Research Articles

Synthesis of dual-sensitive nanocrystalline cellulose-grafted block copolymers of N-isopropylacrylamide and acrylic acid by reversible addition-fragmentation chain transfer polymerization

A core–shell structure of crosslinked poly(2-hydroxyethylmethacrylate) as corona and nanocrystalline cellulose (NCC) as core was synthesized by distillation precipitation polymerization. Then, it was reacted with a chain transfer agent of S-(thiobenzoylthioglycolic) acid to obtain NCC-RA. Homopolymers of N-isopropylacrylamide (NIPAAm) and acrylic acid (AA) as temperature- and pH-sensitive materials, as well as their dual-sensitive block copolymers, were grafted at the surface of NCC-RA by an in situ reversible addition-fragmentation chain transfer polymerization method via R-group approach. Grafting of chain transfer agent and polymer chains at the surface of nanocrystals was studied by X-ray photoelectron (XPS), Fourier transform infrared, and Raman spectroscopies. Thermogravimetric analysis and XPS were also used to study the graft content of chain transfer agent and polymers. Sensitivity of the polymer-grafted NCCs to temperature and pH were studied by UV–visible spectroscopy. By the addition of poly(N-isopropylacrylamide) block to the poly(acrylic acid)-grafted nanocrystals, phase transition is observed at 32 °C. When the poly(acrylic acid) block is the outer layer, phase transition is observed at higher temperatures and pH-responsivity is observed at pH 7.0–10.0. Finally, morphology of the neat and polymer-grafted NCCs was studied by scanning and transmission electron microscopies.

Stimulative nanogels with enhanced thermosensitivity for therapeutic delivery via β-cyclodextrin-induced formation of inclusion complexes

To explore the potential biomedical application of thermoresponsive nanosystems, it is important to enhance their thermosensitivity to improve the controllability in delivery of therapeutic agents. The present work develops multifunctional nanogels with enhanced thermosensitivity through copolymerization of N-isopropylacrylamide (NIPAM) and acrylic acid (AA) in the presence of β-cyclodextrin (β-CD), using N,N′-bis(acryloyl)cystamine (BAC) as a biodegradable crosslinker. The resulting nanogels display significantly improved sensitivity in deswelling (swelling) behavior upon temperature increase (decrease) around body temperature. The nanogels can effectively encapsulate doxorubicin (DOX), which can be released in an accelerated way under microenvironments that mimic intracellular reductive conditions and acidic tumor tissues. Release can also be remotely manipulated by increasing temperature. In vitro study indicates that the nanogels are quickly taken up by KB cells (a human epithelial carcinoma cell line), exerting improved anticancer cytotoxicity, showing their potential for delivery of therapeutic agents beyond anticancer drugs.

Smart polymeric nanoparticles for boron scavenging

Boron is biologically beneficial but only in trace quantities. It is hard to detect and remove from water, as sometimes required in the treatment of residual waters. We have designed an approach based on thermo-responsive polymer nanoparticles containing vicinal diol groups for boron scavenging. The particles have a core of poly(methyl methacrylate) (PMMA) and a thermosensitive shell with a brush composed of a copolymer of N-isopropylacrylamide (NIPAM), 2-aminoethyl methacrylate (AEMH), and either d-gluconoamidoethyl methacrylate (GAEM) or monodiol methacrylate (MDM) boron chelating monomers. The nanoparticles show boron removal efficiencies of up to 96%, with removal of phenylboronic acid being more efficient than that of boric acid. The best boron scavenging efficiency was obtained for the higher specific surface area particles containing d-gluconoamidoethyl groups. At temperatures above ca. 35°C the particle shell collapses, inducing particle aggregation which allows simple separation and recovery of the nanoparticles. These can be subsequently used for boron scavenging, without loss of efficiency.

Facile synthesis of tunable core-shell particles via one-step copolymerization

A type of tunable particles consisting of a soft poly(N-isopropylacrylamide) (PNIPAM) core and a solid shell were directly synthesized in toluene via a facile one-pot copolymerization of N-isopropylacrylamide (NIPAM), (3-Methacryloyloxypropyl)methyldiethoxysilane (MADS), and N,N′-methylenebis(2-propenamide) (MBA). Of particular concern is the shells’ potential to burst due to the swelling and expansion of the PNIPAM core after soaking in water, resulting in an outflow of the core. The toughness of the particle shells could be tuned by altering the feed ratio of MADS or MBA relative to NIPAM, resulting in a series of morphologies that varied from resembling a broken egg to being deformed core-shell spheres. The morphologies could be further modulated by dispersing the particles in different solvents.

Thermo- and electro-dual responsive poly(ionic liquid) electrolyte based smart windows.

Thermo- and electro-dual responsive poly(ionic liquid) (PIL) based electrolytes were synthesized by co-polymerization of N-isopropylacrylamide (NIPAM) with (or without) 3-butyl-1-vinyl-imidazolium bromide ([BVIm][Br]) using diallyl-viologen (DAV) as both the cross-linking agent and electrochromic material.

Wide-range pKa tuning of proton imprinted nanoparticles for reversible protonation of target molecules via thermal stimuli.

pKa tuning of Brønsted acids in synthetic nano-materials is of great importance for the design of ion exchange and bio-/molecular-separation media and polymer catalysis. It has been reported that hydrogel nanoparticles with carboxylic acids that show large and reversible pKa shifts in response to thermal stimuli can be prepared by copolymerization of N-isopropylacrylamide (NIPAm), acrylic acids (AAc) and N,N'-methylene bisacrylamide (BIS) via the proton imprinting polymerization process. However, the reported range of pKa shifts is limited to the range of 5.3 to 7.5. In this study, we report a procedure to prepare proton imprinted NPs that show pKa shifts in the tuned pKa range and demonstrate applications of the NPs. pKa values ranging from 4.3 to 8.7 were achieved by designing the structure of monomers containing carboxylic acids and applying the proton imprinting procedure. It was demonstrated that proton-imprinted NPs with different pKa values could be used for the reversible and selective protonation of target molecules which have specific pKa values. Our results establish the generality of the proton imprinting procedure and provide a guide for designing stable and inexpensive materials for sophisticated purification processes.

The interaction between polyelectrolyte microgels of N-isopropylacrylamide copolymers and aqueous solutions of alcian blue

The temperature influence on the behavior of microgels based on poly-N-isopropylacrylamide (PNIPA) homopolymer, N-isopropylacrylamide copolymers with sodium methacrylate (PNIPA/MANa), sodium styrenesulfonate (PNIPA/SSNa), and sodium vinylsulfonate (PNIPA/VSNa) was studied. The comparative analysis of the temperature-induced collapse of macro- and microgels was conducted. The interaction between alcian blue and PNIPA, PNIPA/SSNa, PNIPA/VSNa, and PNIPA/MANa gels was studied. The research showed that dye sorption leads to the contraction of oppositely charged microgels. The sorption effectiveness depends on the nature of the ionogenic units. The dye sorption by PNIPA/SSNa microgels is more effective than the sorption by the corresponding macrogels. The AB sorption by PNIPA/MANa microgels is less than the sorption by the corresponding macrogels and by the PNIPA/SSNa microgels. The interaction properties are connected to the structure of the crosslinked polymer chains in the microgels.

Versatile Synthesis of Amino Acid Functional Polymers without Protection Group Chemistry

The copolymerization of N-isopropylacrylamide (NiPAm) with aldehyde functional monomers facilitates postpolymerization functionalization with amino acids via reductive amination, negating the need for protecting groups. In reductive amination, the imine formed from the condensation reaction between an amine and an aldehyde is reduced to an amine. In this work, we categorize amino acids into four classes based on the functionality of their side chains (acidic, polar neutral, neutral, and basic) and use their amine groups in condensation reactions with aldehyde functional polymers. The dynamic nature of the imine as well as the versatility of reductive amination to functionalize a polymer with a range of amino acids is highlighted. In this manner, amino acid functional polymers are synthesized without the use of protecting groups with high yields, demonstrating the high functional group tolerance of carbonyl condensation chemistry and the subsequent reduction of the imine. Prior to the reduction of the imine bond, transimination reactions are used to demonstrate dynamic polymers that shuffle from a glycine- to a histidine-functional polymer.

Synthesis and Drug Delivery Application of Thermo- and pH-Sensitive Hydrogels: Poly(β-CD-co-N-Isopropylacrylamide-co-IAM).

Copolymerization of N-isopropylacrylamide (NIPAM), itaconamic acid (IAM; 4-amino-2-methylene-4-oxobutanoic acid) and β-cyclodextrin was investigated in this study. β-cyclodextrin was at first modified by reacting with allyl glycidyl ether to substitute its OH end groups with moieties containing double bonds to facilitate the subsequent radical copolymerization with NIPAM and IAM. It was reported that poly(NIPAM-IAM) can respond to the change of temperature as well as pH value. In this study, the structure of β-cyclodextrin was introduced to poly(NIPAM-IAM) copolymers because of its cavity structure capable of encapsulating a variety of drug molecules. The tri-component copolymers, poly(CD-NIPAM-IAM), were synthesized with different monomeric ratios of NIPAM/IAM/β-CD and the hydrogels of the tri-component copolymers were also synthesized by additionally adding N,N′-methylenebisacrylamide as a cross-linking agent. The results show that the lower critical solution temperature (LCST) of the copolymer (or hydrogel) increases as the molar fraction of IAM increases. The transmission electron microscopic (TEM) images of linear copolymers (no cross-linking) show that molecules undergo self-assembly to have a distinct core–shell structure, compared to poly(CD-NIPAM) which contains no IAM. On the other hand, the scanning electron microscopic (SEM) images of hydrogels show that the pores gradually become sheet-like structures as the molar fraction of IAM increases to enhance the water absorption capacity. In order to exhibit the thermal and pH sensitivities of poly(CD-NIPAM-IAM) as the drug carrier, the drug release of the newly synthesized hydrogels at 37 °C and different pH values, pH = 2 and pH = 7.4, was investigated using atorvastatin which was used primarily as a lipid-lowering drug. The drug release experimental result shows that poly(CD-NIPAM-IAM) as a drug carrier was pH-sensitive and has the largest release rate at pH = 7.4 at 37 °C, indicating it is useful to release drugs in a neutral or alkaline (intestinal) environment.

Acellular mineral deposition within injectable, dual‐gelling hydrogels for bone tissue engineering

This study sought to characterize the composition and morphology of acellular mineralization occurring in thermally and chemically gelable hydrogels comprising copolymers of hydrophobic N-isopropylacrylamide as a function of hydrogel hydrophobicity and culture medium formulation. The deposition of calcium phosphate (CaP) mineral was hypothesized to occur with increasing hydrogel hydrophobicity and presence of serum proteins in the culture medium. Two hydrogel compositions with a solid content of 15 and 20 wt % were examined in serum-containing and nonserum-containing media for 0, 14, 28, and 56 days. Using biochemical assays, calcium, but not phosphate content, was found to significantly increase over time in hydrophobic hydrogels soaked in cell culture medium with fetal bovine serum. Significant increases in the calcium to phosphate ratio were observed within these hydrogels from day 0 to 56, with mineralization indicated by von Kossa histological staining. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDX) were used to analyze CaP mineral characteristics. No crystalline apatitic reflection peaks were observed using XRD, which was supported by the lack of observable mineral deposits as observed using SEM/EDX. However, FTIR showed the presence of new absorption peaks in the serum-containing samples at 28 and 56 days which suggested the formation of an immature apatitic-like mineral. The ability to undergo hydrophobicity-dependent and protein-mediated mineralization demonstrates the potential of these dual-gelling hydrogels as acellular self-mineralizing materials for bone tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 110-117, 2017.

Temperature-Responsive Nanofibrillar Hydrogels for Cell Encapsulation.

Natural extracellular matrices often have a filamentous nature, however, only a limited number of artificial extracellular matrices have been designed from nanofibrillar building blocks. Here we report the preparation of temperature-responsive nanofibrillar hydrogels from rod-shaped cellulose nanocrystals (CNCs) functionalized with a copolymer of N-isopropylacrylamide and N,N'-dimethylaminoethyl methacrylate. The composition of the copolymer was tuned to achieve gelation of the suspension of copolymer-functionalized CNCs at 37 °C in cell culture medium and gel dissociation upon cooling it to room temperature. The mechanical properties and the structure of the hydrogel were controlled by changing copolymer composition and the CNC-to-copolymer mass ratio. The thermoreversible gels were used for the encapsulation and culture of fibroblasts and T cells and showed low cytotoxicity. Following cell culture, the cells were released from the gel by reducing the temperature, thus, enabling further cell characterization. These results pave the way for the generation of injectable temperature-responsive nanofibrillar hydrogels. The release of cells following their culture in the hydrogels would enable enhanced cell characterization and potential transfer in a different cell culture medium.

Conformation-dependent affinity of protein-like copolymers for small ligands. Poly(NIPAM-co-sodium styrene sulfonate) – Polyamines systems

Abstract The thermoresponsive copolymers of N-isopropylacrylamide (NIPAM) with sodium styrene sulfonate (SSS) exhibit a protein-like transition behavior in aqueous medium. They undergo a coil-to-globule conformational transition without phase separation. In the present work we investigated a conformation-dependent binding of polyfunctional ligands to the protein-like NIPAM- b -SSS copolymers modelling their functional behavior by analogy with the enzyme-substrate interaction. Natural polyamines of various charge (putrescine, spermidine and spermine) were used as the polyfunctional ligands. The polyamine-copolymer binding was evaluated by high-sensitivity differential scanning calorimetry. The dependences of the transition parameters (transition temperature, enthalpy, heat capacity increment and thermodynamic width) for two NIPAM- b -SSS copolymers of low and high charge density on the polyamine concentrations were obtained. In general, they pointed to a preferential binding of polyamines to the copolymers in globular conformation, that is particularly pronounced for the copolymer of low charge density. The excess transition enthalpy was introduced as an apparent measure of the ligand binding to the copolymer. The apparent binding constants increased in the series putrescine

Self-Activated Healable Hydrogels with Reversible Temperature Responsiveness.

The self-healable polymer hydrogel along with reversible temperature responsiveness was prepared through self-catalyzed dynamic acylhydrazone formation and exchange without any additional stimulus or catalyst. The hydrogel was prepared from a copolymer of N-isopropylacrylamide and acylhydrazine P(NIPAM-co-AH) cross-linked by PEO dialdehyde. Besides self-healed under catalysis of acid and aniline, the hydrogel can also self-heal activated by excess of acylhydrazine groups. Without interference of catalyst during the hydrogel formation and self-healing, this kind of hydrogel prepared from biocompatible polymers can be used in more areas including biotechnology and be more persistent. The hydrogel with a large part of the PNIPAM segment also showed temperature responsiveness around body temperature influenced by the variation in group ratio. This self-healable hydrogel has great potential application in areas related to bioscience and biotechnology.

Preparation of thermoresponsive fluorescent carbon dots for cellular imaging

Nowadays, carbon dots (CDs) have aroused widespread interest due to their chemical stability, biocompatibility as well as low toxicity. Herein, polymerizable CD monomers were synthesized through amidation between hydrophobic CDs and methacryloyl chloride, which has emerged as a facile method for preparing various fluorescent CD monomers. The fluorescent polymerizable CDs were copolymerized with N-isopropylacrylamide (NIPAM) to form thermoresponsive fluorescent nanoparticles. The poly(NIPAM) (PNIPAM) grafted hydrophobic CDs (CDs-g-PNIPAM) have excellent dispersivity in water, rendering hydrophobic CDs with fluorescence properties in aqueous media. Moreover, CDs-g-PNIPAM nanocomposites show a remarkable thermoresponsive behavior, and the fluorescence intensity decreases progressively with increase in temperature. Cytotoxicity tests show that CDs-g-PNIPAM nanocomposites have great biocompatibility. When the CDs-g-PNIPAM nanocomposites were cultured with HaCaT cells at a concentration of 2000 µg mL−1, cell viability was maintained over 85%. Benefiting from the copolymerization of NIPAM, the excitation-independent fluorescence of CDs-g-PNIPAM nanocomposites can be used for cellular labeling and show long-term biostability in a cellular environment. © 2016 Society of Chemical Industry

Ternary copolymers of acrylic acid, N-isopropylacrylamide, and butyl acrylate: Synthesis and aggregative behavior in dilute solutions

Narrowly dispersed hydrophilic block and random copolymers of acrylic acid and N-isopropylacrylamide of various compositions and molecular masses are synthesized for the first time by controlled radical polymerization via the reversible addition-fragmentation chain-transfer mechanism. The copolymers are used for the synthesis of ternary copolymers with n-butyl acrylate. As shown by dynamic light scattering, the resulting amphiphilic copolymers can form stable dispersions in diluted aqueous solutions. It is found that the effective hydrodynamic radii of dispersion particles may be controlled via variation both in the primary structure of the ternary copolymer, i.e., the amount and sequence of hydrophilic and hydrophobic units, and in the external stimuli, i.e., the temperature and pH of a solution.

Highly sensitive multiresponsive photonic hydrogels based on a crosslinked Acrylamide- N-isopropylacrylamide (AM-NIPAM) co-polymer containing Fe3O4@C crystalline colloidal arrays

Multiresponsive photonic hydrogels (MRPHs) were prepared by magnetically controlled self-assembly of Fe3O4@C nanoparticles and these are sensitive to temperature, humidity, compression, tension and ethanol. This exhibits brilliant structural color thanks to the combination of AM and NIPAM monomers. Along with the increase of compression and tension on the MRPHs, the reflection peak of the samples blue shifts. When exposed MRPHs in environments with different humidity, its structure color red shifts as the humidity increases from 33% RH to 95% RH. Besides, the reflection peak redshift was observed when the MRPHs was immersed in absolute ethyl alcohol. This work may provide a new way to prepare smart photonic hydrogel with integrated functions of mechano-, humidity-, temperature- and solvent- responses.

Poly(N-isopropylacrylamide) hydrogels cross-linked by α,α-trehalose diacetals as thermo-responsive and acid-degradable carriers for drug delivery

A series of novel thermo-responsive hydrogels cross-linked by acid-degradable trehalose diacetals with VPTTs tailored to biologically useful temperatures were obtained by copolymerization of Nisopropylacrylamide with more hydrophilic comonomers: acrylamide, N-(2-hydroxyethyl)acrylamide or N,N-dimethylacrylamide. Due to the properties of the acetal bond, these hydrogels degraded via acid-catalyzed hydrolysis, in the course of which water-soluble terpolymers were formed and trehalose molecules with bioprotective properties were released. The incorporation of hydrophilic comonomers influenced the volume phase transition, swelling capacity, response rate to temperature change, mechanical properties, morphology and the degradation rate in acidic conditions. The release profile of the model drug, propranolol hydrochloride, was found to be dependent on the hydrogel composition, matrix form, and a medium pH. The preliminarily results of cytotoxicity assay suggest, that hydrogels and terpolymers are non-toxic towards L929 mouse fibroblasts.

Photo-swing extraction system for the separation of lanthanide using a pyrene group-containing thermosensitive polymer combined with carbon nanotubes

ABSTRACTA novel photo-swing extraction system for lanthanide separation was developed using a copolymer of acid phosphoxy ethyl methacrylate (Phosmer-M), N-isopropylacrylamide (NIPAM), and (1-pyrene)methyl methacrylate (Phosmer-M/NIPAM/PyMMA). Single-walled carbon nanotubes (CNTs) were successfully dispersed in the Phosmer-M/NIPAM/PyMMA as a result of the π-π interactions of the pyrene groups. The phase transition of the copolymer was successfully induced via photo-irradiation as a result of heat generation by the CNTs. The extraction of Eu(III) was increased by the photo-irradiation because of changes in volume and hydrophobicity of the copolymer. Separation of the lanthanides was improved by the photo-irradiation, especially for the combination of Eu(III)/Sc(III).

Synergetic catalytic effect of α-cyclodextrin on silver nanoparticles loaded in thermosensitive hydrogel

Thermosensitive poly(NIPAAm-co-AMPS) hydrogels were prepared by copolymerization of N-isopropyl acrylamide (NIPAAm) and 2-acrylamido-2-methyl 1-propansulfonic acid (AMPS) by employing N,N′-methylenebis(acrylamide) (BIS) as cross-linker. Uniformly distributed silver nanoparticles (Ag-NP) were obtained within hydrogel networks as nanoreactors via in situ reduction of silver nitrate (AgNO3) using sodium borohydride (NaBH4) as reducing agent. The catalytic properties of Ag-NP-poly(NIPAAm-co-AMPS) hydrogels presented obvious temperature dependence upon the reduction of 4-nitrophenol (4-NP) in aqueous solution. Interestingly, the addition of α-cyclodextrin (α-CD) could further enhance the reduction rate and change the associated activation parameters. This advanced catalytic system with temperature dependence and α-CD synergetic effect presented promising applications in catalytic chemistry.

Investigation of the Thermosensitive Nanosphere Polymer in Removing Organophosphorus Pesticides from Water and Its Isotherm Study (Case Study: Diazinon)

In this research, a novel thermosensitive nanosphere polymer (TNP) was synthesized by copolymerization of N-isopropylacrylamide with 3-allyloxy-1,2-propanediol for the removal of diazinon from water. The characterization of the synthesized adsorbent has been performed by Fourier transform infrared spectrometer, scanning electron microscopy and elemental analysis. Batch adsorption method was performed to investigate the influences of various parameters like pH, temperature and contact time on the adsorption of diazinon. The equilibrium adsorption data of diazinon by TNP was studied by Langmuir, Freundlich, Temkin and Redlich–Peterson model. According to equilibrium adsorption results, the Langmuir, Freundlich and Temkin constants were evaluated to be 0.912 (L/mg), 7.916 (mg/g) (L/mg)1/n and 2.494 respectively at pH 7 and room temperature. Based on Redlich–Peterson model analysis, the equilibrium data for the adsorption of diazinon was conformed well to the Langmuir isotherm model. This method was successfully applied for removal of diazinon from environmental samples. Moreover, in reusing of TNP, the sorption capacity was maintained without any significant change after 10 cycles of sorption–desorption process.