N‐vinylcaprolactam‐based microgels: Synthesis and characterization

Poly(N‐vinylcaprolactam) (PVCL) is well known for its thermoresponsive behavior in aqueous solutions. PVCL combines useful and important properties; it is biocompatible polymer with the phase transition in the region of physiological temperature (32–38 °C). This combination of properties allows consideration of PVCL as a material for design biomedical devices and use in drug delivery systems. In this work, PVCL based temperature‐sensitive crosslinked particles (microgels) were synthesized in a batch reactor to analyze the effect of the crosslinker, initiator, surfactant, temperature, and VCL concentration on polymerization process and final microgels characteristics. The mean particle diameters at different temperatures and the volume phase‐transition temperature of the final product were analyzed. To obtain information about the inner structure of microgel particles, semicontinuous polymerizations were carried out and the evolution of the hydrodynamic average particle diameters at different temperatures of the microgel synthesized was investigated. In the case of microgel particles obtained in a batch reactor the size and the swelling‐de‐swelling behavior as a function of the temperature of the medium can be tuned by modulating the reaction variables. When the microgel particles were synthesized in a semibatch reactor different swelling‐de‐swelling behaviors were observed depending on particles inner structure. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2510–2524, 2008     

N‐vinylcaprolactam‐based microgels: Effect of the concentration and type of cross‐linker

New microgel particles produced by using N‐vinylcaprolactam (VCL) and poly(ethylene glycol) diacrylate (PEGDA) or N,N′‐methylenbisacrylamide (BA) were synthesized in a batch reactor. The influence of the concentration and type of crosslinker on polymerization kinetics and colloidal characteristics of such temperature‐sensitive particles was studied. The partial and total conversion evolutions of VCL, PEGDA, and BA were determined by quantitative ¹H NMR and the average diameters of microgel particles together with the swelling–deswelling behavior were analyzed by means of photon correlation spectroscopy (PCS). Partial and total conversions, final average diameters at collapsed state, and the swelling–deswelling behavior varied as a function of the type of crosslinker. These results were attributed to the higher solubility and stabilizing ability of PEGDA compared with that of BA. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2766–2775, 2008     

N‐vinylcaprolactam‐based microgels for biomedical applications

Three types of poly(N‐vinylcaprolactam)‐based temperature‐sensitive microgel particles were synthesized by emulsion polymerization. The uptake of a model drug (calcein) into the particles was analyzed in terms of the amount of calcein absorbed and equilibrium–swelling degree. By incubating the microgels with primary neuronal cell cultures of embrionary rats, cell viability and biocompatibility tests were carried out. The results show that the driving force for the model drug to penetrate into the microgel particles is H‐bonding associations. On the other hand, cell death was microgel concentration and incubation period dependent. Microgels can be stored in a dried state and resuspended in water when necessary without changing their swelling–deswelling ability. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1173–1181, 2010     

Dual stimuli‐responsive microgels based on photolabile crosslinker: Temperature sensitivity and light‐induced degradation

The synthesis and characterization of a new photocleavable crosslinker is presented here. Dual stimuli‐responsive P(VCL‐co‐NHMA) microgels were prepared by precipitation polymerization of vinylcaprolactam (VCL) with N‐hydroxymethyl acrylamide (NHMA) and the new crosslinker. The microgels had distinct temperature sensitivity as observed in the case of PVCL‐based particles and their volume phase transition temperature (VPTT) shifted to higher temperature with increasing NHMA content. Photolytic degradation experiments were investigated by irradiation with UV light, which led to microgel disintegration caused by cleavage of the photolabile crosslinking points. The degradation behavior of the microgels was conducted with respect to degradation rates by means of the relative turbidity changes. Hence, the microgels could totally degrade into short linear polymers by UV light, thus representing a great potential as new light and temperature dual responsive nanoscale materials. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1676–1685     

Preparation,morphology, and thermoresponsive properties of poly(N‐isopropylacrylamide)‐based copolymer microgels

In this research, thermoresponsive copolymer latex particles with an average diameter of about 200–500 nm were prepared via surfactant‐free emulsion polymerization. The thermoresponsive properties of these particles were designed by the addition of hydrophilic monomers [acrylic acid (AA) and sodium acrylate (SA)] to copolymerize with N‐isopropylacrylamide (NIPAAm). The effects of the comonomers and composition on the synthesis mechanism, kinetics, particle size, morphology, and thermoresponsive properties of the copolymer latex were also studied to determine the relationships between the synthesis conditions, the particle morphology, and the thermoresponsive properties. The results showed that the addition of hydrophilic AA or SA affected the mechanism and kinetics of polymerization. The lower critical solution temperature (LCST) of the latex copolymerized with AA rose to a higher temperature. However, because the strong hydrophilic and ionic properties of SA caused a core–shell structure, where NIPAAm was in the inner core and SA was in the outer shell, the LCST of the latex copolymerized with SA was still the same as that of pure poly(N‐isopropylacrylamide) latex. It was concluded that these submicrometer copolymer latex particles with different thermoresponsive properties could be applied in many fields. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 356–370, 2006     

Dynamic control of volume phase transitions of poly(N‐isopropylacrylamide) based microgels in water using hydrazide‐aldehyde chemistry

We demonstrate that the volume phase transition temperature (VPTT) of copolymer microgel particles made from N‐isopropylacrylamide (NIPAm) and methacryloyl hydrazide (MH) can be tailored in a reversible manner upon the reaction of the hydrazide functional groups with aldehydes. The microgels were synthesized by precipitation polymerization in water. Due to the water‐soluble nature of the MH monomer, the VPTT at which the microgel particles contract shifts to higher values by increasing the incorporated amounts of methacryloyl hydrazide from 0 to 5.0 mol %. The VPTT of the copolymer microgel dispersions in water can be fine‐tuned upon addition of hydrophobic/hydrophilic aldehydes, which react with the hydrazide moiety to produce the hydrazone analogue. This hydrazone formation is reversible, which allows for flexible, dynamic control of the thermo‐responsive behavior of the microgels. The ability to “switch” the VPTT was demonstrated by exposing hydrophilic streptomycin sulfate salt incubated microgel particles to an excess of a hydrophobic aldehyde, that is benzaldehyde. The temperature at which these microgels contracted in size upon heating was markedly lowered in these aldehyde exchange experiments. Transformation into benzaldehyde hydrazone derivatives led to assembly of the microgel particles into small colloidal clusters at elevated temperatures. This control of supracolloidal cluster formation was also demonstrated with polystyrene particles which had a hydrazide functionalised microgel shell. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1745–1754     

Synthesis of biocompatible and thermally sensitive poly(N‐vinylcaprolactam) nanogels via inverse miniemulsion polymerization: Effect of the surfactant concentration

The goal of this study was to develop a new route to prepare thermally responsive polymer nanogels. Poly(N‐vinylcaprolactam) nanogels were prepared via inverse miniemulsion polymerization (W/O) at 70 °C using n‐hexadecane as a nonpolar continuous phase, potassium persulfate as an initiator, and N,N′‐methylenebisacrylamide as a crosslinker. Sorbitan monooleate (Span 80) was used as surfactant and its influence on the polymerization kinetics and on the colloidal characteristics of the nanogels were principally investigated. It was observed that the addition of a strong “lipophobe” is required to stabilize the resulting miniemulsion. The nanogels were characterized in terms of morphology, size, zeta potential, and thermoproperties using transmission electron microscopy and dynamic light scattering. It was observed that all the nanogels obtained collapsed when the lower critical solution temperature (LCST) was raised. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3932–3941, 2010     

Polymer hydrogels of 2‐hydroxyethyl acrylate and acrylic acid obtained by frontal polymerization

In this work, we report on the synthesis and characterization of homopolymers and copolymers of acrylic acid and 2‐hydroxyethyl acrylate prepared by the use of the frontal polymerization (FP) technique. Tetraethyleneglycoldiacrylate was used as a crosslinker and benzoyl peroxide as an initiator. The maximum temperatures reached by the front were in the range between 214 °C and 296 °C. Besides, front velocities ranged between 3.9 and 10.8 cm/min, the latter being one of the highest values reported so far in the FP literature. Differential scanning calorimetry was used to estimate the conversion degree, which was always comprised between 90% and 96%, and to determine the glass transition temperatures, which were found to be dependent on the composition, with values ranging from 13 °C to 168 °C. Moreover, the obtained materials were allowed to swell in aqueous solutions at various pH. The samples exhibit a moderate increase of the swelling ratio percentage (SR%) at pH ≈ 5–6, and a sudden and larger SR% increase at pH ≈ 12–13 depending on the composition, thus indicating the obtainment of pH‐responsive polymer hydrogels. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Lead‐sensitive PNIPAM microgels modified with crown ether groups

A series of lead‐sensitive poly(N‐isopropylacrylamide) microgels with pendant crown ether groups were prepared. Their cation‐sensitive behaviors were studied by dynamic light scattering. When ionic strength is not controlled, adding salts causes the microgel particles to deswell. However, when the salt effect is ruled out by keeping a constant ionic strength, adding Pb²⁺ results in much larger swelling. The Pb²⁺‐induced swelling was explained by the formation of host–guest complex between Pb²⁺ and the pendant crown ether groups, which increases the hydrophilicity of the polymer and accordingly the degree of swelling. The lead sensitivity of the microgels increases with increasing crown ether content. For the modified microgel with the highest crown ether content, it swells to ～430% of its original volume at [Pb²⁺] = 10 mM. Other cations also increase the swelling degree of the modified microgels. The extent of the cation‐induced swelling mainly depends on their affinity to the pendant crown ether groups. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 4120–4127, 2010     

Magnetic poly(N‐isopropylacrylamide) microspheres by dispersion and inverse emulsion polymerization

The aim of this study was to develop novel thermally responsive polymer microspheres with magnetic properties. Dispersion and inverse emulsion copolymerization of N‐isopropylacrylamide (NIPAAm) and N,N′‐methylenebisacrylamide (MBAAm) was investigated in the presence of γ‐Fe₂O₃ nanoparticles. The resulting microspheres were characterized in terms of morphology, size, polydispersity, iron content, and temperature‐dependent swelling using optical microscopy, transmission electron microscopy, scanning electron microscopy, QELS, and AAS. The effects of several variables, such as the concentration of γ‐Fe₂O₃, MBAAm crosslinking agent, Span 80 surfactant, 2,2′‐azobis(2‐methyloctanenitrile) (AMON) initiator, and polymerization temperature on the properties of the microspheres were studied. Swelling and thermoresponsive behavior of the microspheres containing γ‐Fe₂O₃ nanoparticles were also investigated. The microspheres contained about 8 wt % of iron. The presence of magnetic nanoparticles and their concentration changes did not have any significant effect on the temperature sensitivity of the composites. The particles gradually shrink into an increasingly collapsed state when the temperature is raised to 40 °C since the increase in temperature weakens the hydration and PNIPAAm chains gradually become more hydrophobic, which leads to the collapse of the particles. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5884–5898, 2007     

Effect of Gold Nanoparticles on the Thermosensitivity,Morphology, and Optical Properties of Poly(acrylamide–acrylic acid) Microgels

Novel positive thermosensitive microgels of poly(acrylamide–acrylic acid) with embedded gold nanoparticles have been synthesized and characterized by means of dynamic light scattering, UV‐vis spectroscopy, field emission scanning electron microscopy, and transmission electron microscopy. These systems show temperature (upper critical solution temperature‐like volume phase transition) and optical responsiveness making them externally triggered systems.

     

Synthesis and Characterization of Novel pH‐Responsive Polyampholyte Microgels

Summary: We synthesized for the first time novel pH‐responsive polyampholyte microgels consisting of poly(methacrylic acid) and poly(2‐(diethylamino)ethyl methacrylate) (PMAA‐PDEA) that are sterically stabilized with poly(ethylene glycol) methyl ether methacrylate (PEGMEM). These microgels showed enhanced hydrophilic behavior in aqueous medium at low and high pH but become hydrophobic and compact between pH 4 and 6 near the isoelectric point. Dynamic‐light scattering measurements showed that the hydrodynamic radius, R_h of these microgels is approximately 100 nm between pH 4 and 6 and increases to around 140 and 170 nm at pH 2 and 10, respectively. It is evident that the cross‐linked MAA‐DEA microgel that is sterically stabilized with PEGMEM retains the polyampholyte properties in solution.

Sterically stabilized cross‐linked MAA‐DEA microgel.     

Conjugation of arginine–glycine–aspartic acid peptides to thermoreversible N‐isopropylacrylamide polymers

Thermoreversible polymeric biomaterials are finding increased acceptance in tissue engineering applications. One drawback of the polymers is their synthetic nature, which does not allow direct interaction of mammalian cells with the polymers. This limitation may be alleviated by grafting arginine–glycine–aspartic acid (RGD) containing peptides onto the polymer backbone to facilitate interactions with cell‐surface integrins. Toward this goal, N‐isopropylacrylamide (NiPAM)‐based thermoreversible polymers containing amine‐reactive N‐acryloxysuccinimide (NASI) groups were synthesized. Conjugation of RGD‐containing peptides to polymers was demonstrated with ¹H NMR spectroscopy and reverse‐phase high‐pressure liquid chromatography. The conjugation reaction was optimal at 4 °C and pH of 8.0, and increased with the increasing NASI content of polymers. With a peptide grafting ratio of 0.25 mol %, there was no significant change in the lower critical solution temperature of the polymers. Finally, the NASI‐containing polymers, cast as films, on tissue culture polystyrene, were shown to conjugate to RGD‐containing peptides and support C2C12 cell attachment. We conclude that NASI‐containing thermoreversible polymers are amenable for grafting biomimetic peptides to impart cell adhesiveness to the polymers. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3989–4000, 2003     

Synthesis and characterization of graphene‐containing thermoresponsive nanocomposite hydrogels of poly(N‐vinylcaprolactam) prepared by frontal polymerization

Thermoresponsive poly(N‐vinylcaprolactam) nanocomposite hydrogels containing graphene were successfully prepared by frontal polymerization. High concentration of graphene (5.0 mg/mL) was obtained by direct graphite sonication in the self‐same liquid monomer, thus avoiding any chemical manipulation and obtaining “real” graphene as nanofiller instead of one of its more or less oxidized derivative, which is what generally reported in published reports. Furthermore, the corresponding nanocomposites were obtained without using any solvent to be eventually removed. The materials were fully characterized by RAMAN, SEM, and TEM, and their swelling behavior and rheological properties were investigated. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis of low‐polydispersity poly(N‐ethylmethylacrylamide) by controlled radical polymerizations and their thermal phase transition behavior

Controlled radical polymerizations of N‐ethylmethylacrylamide (EMA) by atom transfer radical polymerization and reversible addition‐fragmentation chain transfer processes were investigated in detail for the first time, employing complementary characterization techniques including gel permeation chromatography, ¹H NMR spectroscopy, and matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry. In both cases, relatively good control of the polymerization of EMA was achieved, as revealed by the linear evolution of molecular weights with monomer conversions and the low polydispersity of poly(N‐ethylmethylacrylamide) (PEMA). The thermal phase transitions of well‐defined PEMA homopolymers with polydispersities less than 1.2 and degrees of polymerization up to 320 in aqueous solution were determined by temperature‐dependent turbidity measurements. The obtained cloud points (CPs) vary in the range of 58–68 °C, exhibiting inverse molecular weight and polymer concentration dependences. Moreover, the presence of a carboxyl group instead of an alkyl one at the PEMA chain end can elevate its CP by ～3–4 °C. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 60–69, 2008     

Synthesis of well‐defined 7‐arm and 21‐arm poly(N‐isopropylacrylamide) star polymers with β‐cyclodextrin cores via click chemistry and their thermal phase transition behavior in aqueous solution

The syntheses of well‐defined 7‐arm and 21‐arm poly(N‐isopropylacrylamide) (PNIPAM) star polymers possessing β‐cyclodextrin (β‐CD) cores were achieved via the combination of atom transfer radical polymerization (ATRP) and click reactions. Heptakis(6‐deoxy‐6‐azido)‐β‐cyclodextrin and heptakis[2,3,6‐tri‐O‐(2‐azidopropionyl)]‐β‐cyclodextrin, β‐CD‐(N₃)₇ and β‐CD‐(N₃)₂₁, precursors were prepared and thoroughly characterized by nuclear magnetic resonance and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. A series of alkynyl terminally functionalized PNIPAM (alkyne‐PNIPAM) linear precursors with varying degrees of polymerization (DP) were synthesized via atom transfer radical polymerization (ATRP) of N‐isopropylacrylamide using propargyl 2‐chloropropionate as the initiator. The subsequent click reactions of alkyne‐PNIPAM with β‐CD‐(N₃)₇ and β‐CD‐(N₃)₂₁ led to the facile preparation of well‐defined 7‐arm and 21‐arm star polymers, namely β‐CD‐(PNIPAM)₇ and β‐CD‐(PNIPAM)₂₁. The thermal phase transition behavior of 7‐arm and 21‐arm star polymers with varying molecular weights were examined by temperature‐dependent turbidity and micro‐differential scanning calorimetry, and the results were compared to those of linear PNIPAM precursors. The anchoring of PNIPAM chain terminal to β‐CD cores and high local chain density for star polymers contributed to their considerably lower critical phase separation temperatures (T_c) and enthalpy changes during phase transition as compared with that of linear precursors. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 404–419, 2009     

Hydrogen‐bond‐assisted syndiotactic‐specific radical polymerizations of N‐alkylacrylamides: The effect of the N‐substituents on the stereospecificities and unusual large hysteresis in the phase‐transition behavior of aqueous solution of syndiotactic poly(N‐n‐propylacrylamide)

The radical polymerizations of N‐alkylacrylamides, such as N‐methyl‐(NMAAm), N‐n‐propyl‐(NNPAAm), N‐benzyl‐(NBnAAm), and N‐(1‐phenylethyl)acrylamides (NPhEAAm), at low temperatures were investigated in the absence or presence of hexamethylphosphoramide (HMPA) and 3‐methyl‐3‐pentanol (3Me3PenOH), which induced the syndiotactic specificities in the radical polymerization of N‐isopropylacrylamide (NIPAAm). In the absence of the syndiotactic‐specificity inducers, the syndiotacticities of the obtained polymers gradually increased as the bulkiness of the N‐substituents increased. Both HMPA and 3Me3PenOH induced the syndiotactic specificities in the NNPAAm polymerizations as well as in the NIPAAm polymerizations. The addition of 3Me3PenOH into the polymerizations of NMAAm significantly induced the syndiotactic specificities, whereas the tacticities of the obtained polymers were hardly affected by adding HMPA. In the polymerizations of bulkier monomers, such as NBnAAm and NPhEAAm, HMPA worked as the syndiotactic specificity inducer at higher temperatures, whereas 3Me3PenOH hardly influenced the stereospecificity, regardless of the temperatures. The phase‐transition behaviors of the aqueous solutions of poly(NNPAAm)s were also investigated. It appeared that the poly (NNPAAm) with racemo dyad content of 70% exhibited unusual large hysteresis between the heating and cooling processes. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4575–4583, 2008     

Synthesis of backbone thermo and pH dual‐responsive hyperbranched poly(amine‐ether)s through proton‐transfer polymerization

Stimuli‐responsive hyperbranched polymers have attracted great attention in recent years because of their wide applications in biomedicine. Through proton‐transfer polymerization of triethanolamine and 1,2,7,8‐diepoxyoctane with the help of potassium hydride, a series of novel backbone thermo and pH dual‐responsive hyperbranched poly(amine‐ether)s were prepared successfully in one‐pot. The degrees of branching of the resulting polymers were at 0.40–0.49. Turbidity measurements revealed that hyperbranched poly(amine‐ether)s exhibited thermo and pH dual‐responsive properties in water. Importantly, these responsivities could be readily adjusted by changing the polymer composition as well as the polymer concentration in aqueous solution. Moreover, in vitro evaluation demonstrated that hyperbranched poly(amine‐ether)s showed low cytotoxicity and efficient cell internalization against NIH 3T3 cell lines. These results suggest that these backbone thermo and pH dual‐responsive hyperbranched poly(amine‐ether)s are promising materials for biomedicine. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Heterotactic‐specific radical polymerization of N‐isopropylacrylamide and phase transition behavior of aqueous solution of heterotactic poly(N‐isopropylacrylamide)

Radical polymerization of N‐isopropylacrylamide (NIPAAm) in toluene at low temperatures, in the presence of fluorinated‐alcohols, produced heterotactic polymer comprising an alternating sequence of meso and racemo dyads. The heterotacticity reached 70% in triads when polymerization was carried out at ?40 °C using nonafluoro‐tert‐butanol as the added alcohol. NMR analysis revealed that formation of a 1:1 complex of NIPAAm and fluorinated‐alcohol through C?O···H? O hydrogen bonding induces the heterotactic specificity. A mechanism for the heterotactic‐specific polymerization is proposed. Examination of the phase transition behavior of aqueous solutions of heterotactic poly(NIPAAm) revealed that the hysteresis of the phase transition between the heating and cooling cycles depended on the average length of meso dyads in poly(NIPAAm). © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2539–2550, 2009