Thermoresponsive poly(oligo ethylene glycol acrylates)

Thermoresponsive polymers have been the subject of numerous publications and research topics in the last few decades mostly driven by their easily controllable temperature stimulus and high potential for in vitro and in vivo applications. P(NIPAAm) is the most studied amongst these polymers, but recently other types of polymers are increasingly being investigated for their thermoresponsive behavior. In particular, polymers bearing a short oligo ethylene glycol (OEG) side chain have been shown to combine the biocompatibility of polyethylene glycol (PEG) with a versatile and controllable LCST behavior. These polymers can be synthesized via controlled radical polymerization techniques from various monomers consisting of an OEG chain and a polymerizable group like a (meth)acrylate, styrene or acrylamide. OEG acrylates offer significant advantages over, e.g., OEG methacrylates as the lower hydrophilicity of the backbone facilitates thermoresponsive behavior with smaller, more defined side chains. Furthermore, PEG acrylates can be polymerized using all major controlled radical polymerization techniques, unlike OEG methacrylates. This review will focus on OEG acrylate based (co)polymers and will provide a comprehensive overview of their reported thermoresponsive properties. The combination and comparison of this data will not only highlight the potential of these monomers, but will also serve as a starting point for future studies.     

New degradable polyesters from deoxycholic acid and oligo(ethylene glycol)s

A new class of polyesters was prepared by polycondensation of a bile acid, deoxycholic acid, and an oligo(ethylene glycol) (OEG) with molar mass ranging from 100 to 1500. The chemical structure and composition of the polyesters were confirmed by ¹H‐NMR, Fourier transform infrared spectroscopy and HPLC analysis. Polyester molar masses measured by gel permeation chromatography were between 5000 and 20 000. Thermal stability and glass transition temperature decreased with increasing length of OEG. Hydrolytic degradation was also enhanced by the presence of longer chain OEG. Polyesters obtained from OEG with molar mass ≥ 1000 were water soluble, semicrystalline and thermosensitive. As a function of the OEG length used for their preparation, the new polyesters can be useful for biomedical or industrial applications. © 2012 Society of Chemical Industry     

甲氧基聚氧化乙烯甲基丙烯酸酯的合成

利用甲基丙烯酸、聚乙二醇单甲醚直接酯化合成甲氧基聚氧化乙烯甲基丙烯酸酯,采用预处理的方法制备了甲基丙烯酸高效阻聚剂,同时研究了相对分子质量、反应温度、反应时间对酯化反应的影响规律。结果表明：预处理制备的TN酚醌混合阻聚剂对甲基丙烯酸具有良好阻聚效果,掺量为0.75％时,120 ℃反应20 h无明显聚合;140 ℃时,聚乙二醇单甲醚开始分解,—OH被氧化,产生了C=O;120 ℃时TN催化剂与MPEG混合物能够稳定存在,基本无副反应发生,该体系酯化率可达到99％;MPEG相对分子质量影响反应速度,酯化反应1～4 h酯化率随相对分子质量的增加而降低;当反应4 h时,转化率已达80％。之后反应速度减慢,酯化率随MPEG相对分子质量的变化较小。     

Synthesis of porous poly[oligo(ethylene glycol) methyl ether methacrylate] gels that exhibit thermosensitivity in highly concentrated aqueous NaCl solution

The polymerization of 2-(2-methoxyethoxy)ethyl methacrylate (MEO₂MA) in 20 wt% aqueous ethanol solution and oligo(ethylene glycol) methyl ether methacrylate (OEGMA₃₀₀, M_n = 300 g mol^?1) in water was carried out in the presence of a crosslinker. Polymerization at temperatures above the lower critical solution temperature (LCST) yielded the corresponding porous poly[oligo(ethylene glycol) methyl ether methacrylate] gels by polymerization-induced phase separation. The resulting porous gels showed rapid swelling-deswelling in water. The temperature dependency of the equilibrium swelling ratio of the gels was investigated in several concentrated aqueous NaCl solutions. At 20 °C, the equilibrium swelling ratios of the POEGMA₃₀₀ gel obtained from OEGMA₃₀₀ were largely unaffected by NaCl concentration; however, above 30 °C, they decreased with increasing NaCl concentration. Therefore, the POEGMA₃₀₀ gel showed sharp and high thermosensitivity in highly concentrated aqueous NaCl solutions. Similar swelling behaviors were observed for PMEO₂MA gel, which was prepared from MEO₂MA.     

Polymer gel electrolytes synthesized by photopolymerization in the presence of star-shaped oligo(ethylene glycol) ethers (OEGE)

The photoinitiated cross-linking polymerization of tri(ethylene glycol) dimethacrylate and its copolymerization with cyanomethyl methacrylate in the presence of LiCF₃SO₃ and of various oligo(ethylene glycol) methyl ethers as plasticizer was studied for potential use of the resulting polymer gel electrolytes in lithium batteries. Comparing linear and star-shaped (three and four arm molecules) oligo(ethylene glycol) methyl ethers, the influence of the architecture of the plasticizers on the polymerization course was investigated by means of differential scanning calorimetry. Linear and star-shaped plasticizers with molar masses < 1000 g/mol differ from each other concerning the dependence of their viscosity on their molar mass but not concerning the influence of the viscosity on the polymerization rate. Compared with linear plasticizers, the star-shaped ones have as an essential advantage a distinctly lower tendency to crystallize which is even completely suppressed in some cases. The gels were characterized with regard to the network density of their polymer matrix, to their thermal transitions, thermo-mechanical properties and ionic conductivity. The conductivity of solutions and gels with star-shaped plasticizers was slightly lower than that with linear ones at temperatures above room temperature.     

Conformation of oligo(ethylene glycol) grafted polystyrene in dilute aqueous solutions

Temperature induced conformational changes of poly(p-oligo(ethylene glycol) styrene) (POEGS) in aqueous solutions were investigated by small angle neutron scattering (SANS), neutron transmission and dynamic light scattering (DLS). The molecular weight of the polymer studied was 9400 g/mol with a polydispersity index of 1.18 and each repeat unit of the polymer had four ethylene glycol monomer segments. The polymer was water soluble due to the hydrophilicity of the OEG side chains and these solutions showed lower critical solution temperature (LCST) depending on the concentration of the polymer. Measurements of solution behavior were made as a function of temperature in the range of 25-55 °C for three polymer concentrations (0.1 wt%, 0.3 wt%, and 1.8 wt%). Neutron transmission measurements were used to monitor the amount of polymer which precipitated or remained in solution above the cloud point temperature (T_CP). DLS revealed the presence of large clusters in all solutions both below and above T_CP while SANS provided information on the structure and interactions between individual chains. It was found that in the homogeneous region below T_CP the shape of individual polymers in solution was close to ellipsoidal with the dimensions R_a = 37 Å and R_b = 14 Å and was virtually independent of temperature. The SANS data taken for the most concentrated solution studied (1.8 wt%) were fit to the ellipsoidal model with attractive interactions which were approximated by the Ornstein-Zernike function with a temperature-dependent correlation length in the range of 24-49 Å. The collapse of individual polymers to spherical globules with the radius of 15 Å above T_CP was observed.     

Thermosensitive PMMA core/oligo(ethylene glycol)-based shell microgels as drug carriers in detoxification treatment

The core-shell structured polymer microgels were synthesized by coating the hydrophobic poly(methyl methacrylate) (PMMA) sphere cores with hydrophilic nonlinear poly(ethylene glycol)-based gel shell layer. The uniqueness of these core-shell microgels lies in the integration of the PMMA core microsphere with strong hydrophobicity and the novel oligo(ethylene glycol)-based gel layer with well-defined thermosensitivity for improving loading/release efficacy of two detoxification drugs (chlorpromazine and diltiazem). The hydrophilic shell is composed of hydrophilic copolymer of 2-(2-methoxyethoxy)ethyl methacrylate (MEO₂MA) with oligo(ethylene glycol) methyl ether methacrylates (MEO₅MA). It was found that the molar ratio of two shell monomers n(MEO₂MA)/n(MEO₅MA) of 1:6 was an ideal matching value for production of the P(MEO₂MA)/P(MEO₂MA-co-MEO₅MA) core-shell microgels with tunable volume phase transition temperature and excellent colloidal stability across the physiologically important temperature range. Moreover, chlorpromazine- and diltiazem-loaded microgels can show an obvious thermosensitive release and in vitro sustained-release characteristic up to 80 h.     

Self-assembly of thermo-responsive poly(oligo(ethylene glycol) methyl ether methacrylate)-C60 in water-methanol mixtures

Well-defined statistical copolymer of poly (di(ethylene glycol) methyl ether methacrylate-stat-oligo(ethylene glycol) methyl ether methacrylate-C₆₀ ((PMEO₂MA-stat-POEGMA₃₀₀)-C₆₀) was synthesized via atom transfer radical polymerization (ATRP) reaction and atom transfer radical addition (ATRA) processes. The lower critical solution temperature (LCST) of PMEO₂MA-stat-POEGMA₃₀₀ increased from 42 to 95 °C when the amounts of methanol was increased from 0 to 30 vol%, beyond which the LCST could not be quantified. Similarly, the LCST of (PMEO₂MA-stat-POEGMA₃₀₀)-C₆₀ also increased with methanol content, however it was lower than PMEO₂MA-stat-POEGMA₃₀₀ for all methanol/water compositions. The CMC of (PMEO₂MA-stat-POEGMA₃₀₀)-C₆₀ increased with increasing methanol content, suggesting that methanol is a better solvent for PMEO₂MA-stat-POEGMA₃₀₀ segment. The amphiphilic (PMEO₂MA-stat-POEGMA₃₀₀)-C₆₀ structure formed spherical micelles in water/methanol mixture, and larger micelles were formed at higher methanol content. The hydrodynamic radius (R_h) remained constant at temperature below the LCST. It increased dramatically at temperature greater than the LCST, and the (R_g/R_h) increased from ∼0.75 to ∼1.0. We believe that the (PMEO₂MA-stat-POEGMA₃₀₀) coronas dehydrate at higher temperature, and the micelles associate to form larger aggregates. In water/methanol mixtures, core-shell micelles and large compound micelles are produced below and above the LCST respectively.     

Hydrolysis‐improved thermosensitive polyorganophosphazenes with α‐amino‐ω‐methoxy‐poly(ethylene glycol) and amino acid esters as side groups

A series of hydrolysis‐improved thermosensitive polyorganophosphazenes with α‐amino‐ω‐methoxy‐poly(ethylene glycol) (AMPEG) and amino acid esters (AAEs) of ‘N,N‐systems’ was synthesized, and their properties were evaluated in comparison with the thermosensitive polyorganophosphazenes with methoxy‐poly(ethylene glycol) (MPEG) and AAEs of ‘O,N‐systems’, by means of ³¹P NMR spectroscopy, gel permeation chromatography (GPC) and differential scanning calorimetry (DSC). Most of the present polymers showed a lower critical solution temperature (LCST) in the range 32.0–79.0 °C, depending on the kinds of AAE, length of AMPEG and the mol ratio of the two substituents. These polymers exhibited higher LCSTs and faster degradation rates than the MPEG‐based polymers. The aqueous solution of poly(ethyl glycinate phosphazene)‐graft‐poly(ethylene glycol) [NP(GlyEt)_0.94(AMPEG350)_1.06]_n did not show an LCST, which is presumed to be due to its high hydrophilicity, in contrast to [NP(GlyEt)_1.01(MPEG350)_0.99]_n which showing an LCST at 77.5 °C. On the other hand, the polymers with a high content of AAE or with hydrophobic amino acids such as L ‐aspartic acid and L ‐glutamic acid, have shown a similar LCST to those of the MPEG‐based polymers. The half‐lives (t_1/2) for hydrolysis of [NP(AMPEG350)_1.06(GlyEt)_0.94]_n at pH 5, 7.4 and 10 were 9, 16, and 5 days, respectively, which are almost 2.5 to 4 times faster than that of the MPEG‐based polymers. The LCST of the present N,N‐polymers has been shown to be more influenced by salts such as NaCl (‘salting‐out’ effect) and tetrapropylammonium bromide (TPAB) (‘salting‐in’ effect) compared with the ‘O,N‐system’. Such differences of the ‘N,N‐systems’ from the ‘O,N‐systems’ in thermosensitivity, hydrolysis behavior and salt effect seem to be due to the higher hydrophilicity of the amino group in AMPEG. Copyright © 2005 Society of Chemical Industry     

Comb-shaped chitosan derivatives having oligo(ethylene glycol) side chains

Summary Monoaldehydes have been synthesized from tri- and tetra(ethylene glycol) monosubstituted derivatives and introduced into chitosan by the reductive alkylation technique to give comb-shaped polysaccharide hybrids. The reaction of chitosan with the aldehydes in the presence of sodium cyanoborohydride proceeded efficiently to give chitosan derivatives having oligo(ethylene glycol) side chains at the amino groups. The products were characterized by high affinity for organic solvents as well as water in sharp contrast to the original chitin and chitosan. They showed significant adsorption capacity toward metal cations. Received: 6 November 1998/Revised version: 15 February 1999/Accepted: 22 February 1999     

Biocompatible,ionic‐strength‐sensitive,double‐network hydrogel based on chitosan and an oligo(trimethylene carbonate)–poly(ethylene glycol)–oligo(trimethylene carbonate) triblock copolymer

A double‐network (DN) hydrogel was prepared through the sequential photopolymerization of oligo(trimethylene carbonate) (TPT)‐block‐poly(ethylene glycol)‐block‐oligo(trimethylene carbonate) diarylate and methacrylated chitosan (CS–MA). The swelling behavior and mechanical properties of the hydrogels were tunable via the control of the concentration of CS–MA. Under physiological conditions, the fracture stress of the DN hydrogel reached 3.4 MPa; this was more than twice that of the corresponding TPT‐block‐poly(ethylene glycol)‐block‐TPT single network (1.6 MPa). At high ionic strength, the fracture stress of the DN hydrogel reached 6.4 MPa. The DN hydrogel exhibited good cytocompatibility, as revealed by a live–dead assay. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42459.     

Polyurethane elastomers based on molecular weight advanced poly(ethylene ether carbonate) polyols. IV. Effects of poly(propylene glycol) modified diols

A series of polyurethane elastomers with a (A{BC}_m)n type of structure have been prepared and characterized based on poly(propylene glycol) modified poly(ethylene ether carbonate) polyols, where the poly(propylene glycol) content and block length were varied systematically. Strength and modulus properties showed a marked dependence on modifier level and exhibited synergistic property improvements at 25–50 wt % modifier, relative to both unmodified poly(ethylene ether carbonate) diol and poly(propylene glycol) controls. DMA results indicated an increased modulus for the modified plaques throughout the rubbery plateau region, with higher thermal dissociation temperatures. Excellent organic solvent resistance was maintained with 25–50 wt % poly(propylene glycol) modification in the soft segment. Chemical structure of the polyurethane elastomers was established by proton and ¹³C-NMR spectroscopy. The morphology of these modified polyurethanes appears to be quite complex. Since the modified soft segments are block copolymers of blocks with a tendency toward immiscibility, some microphase separation within the soft segment domains of the polyurethane polymers might be expected. The soft segment T_g is highest where properties are maximized, suggesting changes in phase mixing. © 1992 John Wiley & Sons, Inc.     

Engineering oligo(ethylene glycol)-based thermosensitive microgels for drug delivery applications

Novel oligo(ethylene glycol)-based thermosensitive microgels with well engineered core-shell structures were developed for storage and delivery of chemotherapeutic agents. The core is consisted of hydrophobic poly[2-(2-methoxyethoxy)ethyl methacrylate], while the shell is consisted of hydrophilic copolymer of 2-(2-methoxyethoxy)ethyl methacrylate with oligo(ethylene glycol) methyl ether methacrylates. These core-shell microgels exhibit tunable volume phase transition temperature and excellent colloidal stability across the physiologically important temperature range. The thickness of the hydrophilic shell can control the collapsing degree (or mesh size) of the hydrophobic core network, which can be utilized to significantly increase the loading capacity of the model hydrophobic drugs dipyridamole by tailoring the shell thickness of microgels. While the microgels are nontoxic, the drug molecules released from the microgels remain active to kill the cancer cells. The presented results provide important guidelines for the rational design of core-shell structured polymeric microgels for drug uptake and release applications.     

Synthesis and surface‐active properties of a trisiloxane‐modified oligo(propylene oxide‐block‐ethylene oxide) wetting agent

Polydisperse 1,1,1,3,5,5,5‐heptamethyltrisiloxane‐oligo(propylene oxide‐block‐ethylene oxide) wetting agents were synthesized through the hydrosilylation of 1,1,1,3,5,5,5‐heptamethyltrisiloxane (HMTS) with active hydrogen and allyl oligo(propylene oxide‐block‐ethylene oxide) [allyl oligo(PO‐b‐EO)] with hexachloro dihydrogen platinate(IV) as a catalyst. Allyl oligo(PO‐b‐EO) with a hydrophilic–hydrophobic balance was synthesized through the combination of propylene oxide (PO) and ethylene oxide with allyl alcohol. The wetting agents with a hydrophilic–hydrophobic balance were synthesized. The aqueous solutions of the wetting agents (0.1 wt %) were almost visibly turbid. An increase in the number of hydrophobic groups of HMTS and PO for the wetting agents resulted in a lower critical solution temperature. Lower surface tensions of 20–25 dyn/cm were found above the critical micelle concentration (cmc), and they decreased with an increase in the number of hydrophobic groups. The cmc's were below 0.01 wt %, decreasing with as the number of hydrophobic groups increased. The wetting power and emulsion stability for the oil‐in‐water systems increased as the concentration of the wetting agents increased, and they decreased as the number of hydrophobic groups increased. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 3292–3302, 2004     

Glucose recognition capabilities of hydroxyethyl methacrylate‐based hydrogels containing poly(ethylene glycol) chains

A configurational biomimetic imprinting technique was used to prepare recognition sites for glucose in copolymers of 2‐hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA) prepared with crosslinking agents containing poly(ethylene glycol) (PEG). We report on the structure, diffusive, and recognition characteristics of these gels, the effect of the type and ratio of crosslinking agent, as well as the template/comonomer ratios on glucose binding ability. The highest equilibrium glucose binding was found as 2.67 mg/g dry polymer when PEG monomethacrylate (PEGMMA) was used in combination with tetra ethylene glycol dimethacrylate (TEGDMA) (50%) as a crosslinking agent. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 103: 432–441, 2007     

Self-assembly and drug release control of dual-responsive copolymers based on oligo(ethylene glycol)methyl ether methacrylate and spiropyran

Iranian Polymer Journal - To compare the synthesis and drug release of random and block copolymers, random and block copolymerizations of oligo(ethylene glycol)methyl ether methacrylate (OEGMA) and...     

Tuning the thermoresponsive properties of poly(oligo(propylene glycol) methacrylate) hydrogels via gradient copolymerization with 2-hydroxyethyl methacrylate

Gamma radiation was used to prepare copolymer hydrogel libraries based on oligo(propylene glycol) methacrylate (OPGMA) and 2-hydroxyethyl methacrylate (HEMA); a complete screening in composition of P(OPGMA/HEMA) copolymers was elaborated from 0% to 100% of OPGMA. Determination of gel fraction was performed as the first step after radiation induced synthesis. Tuning of the volume phase transition temperature (VPTT) of P(OPGMA/HEMA) copolymeric hydrogels was investigated by swelling study. Additional characterization of structure and properties was conducted by FTIR, DSC, and UV-Vis spectroscopy. All results indicate that new P(OPGMA/HEMA) copolymeric hydrogels have wide diversity in thermoresponsive properties which strongly depend on their composition.     

Comparison of reaction kinetics and gelation behaviors in atom transfer, reversible addition-fragmentation chain transfer and conventional free radical copolymerization of oligo(ethylene glycol) methyl ether methacrylate and oligo(ethylene glycol) dimethacrylate

The reaction kinetics and gelation behavior in atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain transfer (RAFT), and conventional free radical copolymerizations (FRP) of oligo(ethylene glycol) methyl ether methacrylate (OEGMEMA) and oligo(ethylene glycol) dimethacrylates (OEGDMAs) were investigated and compared with respect to the polymerization rate, gel point, and the evolution of network with vinyl conversion. All the three systems experienced autoacceleration in the reaction rate but occurred at different regions of vinyl conversion, caused by diffusion-controlled radical reactions: termination in the FRP, addition in the RAFT, and deactivation in the ATRP, respectively. In the FRP, significant amount of gel materials was collected by solvent extraction far before the onset of macro-gelation detected by an abrupt increase in complex viscosity. However, in the RAFT and ATRP, no gels were found until the systems approached their macro-gelation points. The observation suggests limited intramolecular crosslinking/cyclization reactions in the ATRP and RAFT systems. This is because the slow growth of primary chains (ATRP and RAFT in hours versus FRP in seconds) allowed adequate chain relaxation and diffusion of reacting species. The gel materials thus synthesized by ATRP and RAFT are expected to be more homogeneous in network structure than that by FRP.     

Preparation and biodegradation of copolyesters based on poly(ethylene terephthalate) and poly(ethylene glycol)/oligo(lactic acid) by transesterification

The poly(ethylene terephthalate‐co‐ethyleneoxide‐co‐DL ‐lactide) copolymers were successfully prepared by the melt reaction between poly(ethylene terephthalate), poly(ethylene glycol), and DL ‐oligo(lactic acid) without any catalysts. The transesterification between ethylene terephthalate, ethyleneoxide, and lactide segments during the reaction was confirmed by the ¹H NMR analysis. The effect of reaction temperatures and the starting feed ratios on the molecular microstructures, molecular weights, solubility, thermal properties, and degradability of the copolyesters was extensively studied. The values of crystallization temperature, melting temperature, crystallization, and melting enthalpy of the copolyesters were found to be influenced by the reaction temperatures, starting feed ratios, etc. The copolyesters showed good tensile properties and were found to degrade in the soil burial experiments during the period of 3 months. The morphology of the copolyester films were also investigated by scanning electron microscopy during soil burial degradation. POLYM. ENG. SCI., 2010. © 2009 Society of Plastics Engineers     

Synthesis of poly(propylene glycol)‐grafted polyimide precursors and preparation of nanoporous polyimides

A novel approach to prepare a polyimide nanofoam was explored by using a polyimide precursor grafted with a labile poly(propylene glycol) (PPG) oligomer. The PPG‐grafted polyimide precursor, poly((amic acid)‐co‐(amic ester)), was synthesized via partial esterification of poly(amic acid) derived from pyromellitic dianhydride (PMDA) and 4,4′‐oxydianiline (ODA) with bromo‐terminated poly(propylene glycol) in the presence of K₂CO₃ in hexamethylphosphoramide and N‐methylpyrrolidone. The precursor polymer film was spin‐coated onto a glass substrate, then imidized at 200 °C under nitrogen, and subsequently the PPG graft was decomposed by heating the film at 300 °C for 9 h in air, resulting in the PMDA/ODA polyimide nanofoam. The precursor polymers, polyimides and foamed polyimides were characterized by a variety of techniques including ¹H‐NMR spectroscopy, Fourier‐transform infrared (FT‐IR) spectroscopy, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The homogeneously distributed nano‐sized pores of 20–40 nm were observed by transmission electron microscopy (TEM) of the foamed polyimide. Copyright © 2004 Society of Chemical Industry