Methacrylamide Polymers Research Articles

Novel Methacrylamide Polymers Based on Thiazole and Styrene: A Study on Synthesis, Characterization, and Determination of Monomer Reactivity Ratios

In this study, firstly, a thiazole methacrylamide (TMAAm) monomer was synthesized from methacryloyl chloride with 2-aminothiazole. Later on, a series of copolymers of 2-thiazole methacrylamide (TMAAm) with styrene (St) using strange compositions in the feed has been prepared in solution via radical at 70 oC with AIBN as initiator. The structure of the copolymers was elucidated by FT-IR, 1H-NMR, and 13C-NMR spectroscopy methods. The compositions of the copolymers were determined from the nitrogen (N) difference according to the elemental analysis results. Monomer reactivity ratios; The rTMAAm and rSt, Fineman-Ross (FR), Kelen-Tüdös (KT) linear methods, and the error method model in non-linear variables were calculated with the computer program RREVM. The molecular weights and heterogeneity indices of the copolymers were determined by the GPC method. The thermal stability of the copolymers was investigated by thermogravimetry (TG) measurements.

Synthesis, characterization, thermal and kinetic properties of chalcone methacrylamide polymers containing halogen group in side chain

Synthesis, characterization, thermal and kinetic properties of chalcone methacrylamide polymers containing halogen group in side chain

Synthesis, characterization and thermal properties of chalcone methacrylamide polymers containing methoxy group in side chain

Synthesis, characterization and thermal properties of chalcone methacrylamide polymers containing methoxy group in side chain

N-Alkyl Methacrylamide Polymers as High Performing Kinetic Hydrate Inhibitors

Homo- and copolymers of N-alkyl methacrylamides with varying alkyl pendant groups have been synthesized and investigated for their performance as kinetic hydrate inhibitors (KHIs) in slow constant ...

Polymers of N-(Pyrrolidin-1-yl)methacrylamide as High Cloud Point Kinetic Hydrate Inhibitors

Formation of gas hydrates is a major problem in flowlines where gas and water are transported together, and can lead to blockages, downtime, economic losses, and potential accidents. One way of preventing gas hydrates from forming is by injection of kinetic hydrate inhibitors (KHIs). KHIs are typically water-soluble polymers, often containing amide pendant groups. Based on our previous work on high cloud point polymers of N,N-dimethylhydrazidoacrylamide (polyDMHAM) and N,N-dimethylhydrazidomethacrylamide (polyDMHMAM), we have now synthesized a series of N-(pyrrolidin-1-yl)methacrylamide polymers (polyNPyMA) which contains a pyrrolidine-substituted hydrazido pendant group. These polymers show improvement on all previous hydrazido polymers as they exhibit improved KHI performance while having no cloud point in deionized water or 7 wt % aqueous NaCl up to 95 °C. Their performance as KHIs have been investigated using a high-pressure gas hydrate rocker rig at a pressure of 76 bar using a structure II forming n...

Dehydroascorbic Acid and pGPMA Dual Modified pH-Sensitive Polymeric Micelles for Target Treatment of Liver Cancer

In clinical therapy, the poor prognosis of hepatocellular carcinoma (HCC) is mainly attributed to the failure of chemotherapeutical agents to accumulate in tumor as well as lack of potency of tumor penetration. In this work, we developed actively tumor-targeting micelles with pH-sensitive linker as a novel nanocarrier for HCC therapy. These micelles comprised biodegradable poly(ethylene glycol)-poly(aspartate) polymers, in which paclitaxel can be covalently conjugated to pAsp via an acid-labile acetal bond to form pH-responsive structures. In vitro drug release studies showed that these structures were stable in physiological condition, whereas collapsed once internalized into cells due to the mildly acidic environment in endo/lysosomes, resulting in facilitated intracellular paclitaxel release. In addition, dehydroascorbic acid and guanidinopropyl methacrylamide polymers were decorated on the surface of micelles to achieve specific tumor accumulation and tumor penetration. Cellular uptake and in vivo imaging studies proved that these micelles had remarkable targeting property toward hepatocarcinoma cells and tumor. Enhanced anti-HCC efficacy of the micelles was also confirmed both in vitro and in vivo. Therefore, this micellar system may be a potential platform of chemotherapeutics delivery for HCC therapy.

Immunomodulatory Therapy of Inflammatory Liver Disease Using Selectin-Binding Glycopolymers.

Immunotherapies have the potential to significantly advance treatment of inflammatory disease and cancer, which are in large part driven by immune cells. Selectins control the first step in immune cell adhesion and extravasation, thereby guiding leukocyte trafficking to tissue lesions. We analyzed four different highly specific selectin-binding glycopolymers, based on linear poly(2-hydroxypropyl)-methacrylamide (PHPMA) polymers. These glycopolymers contain either the tetrasaccharide sialyl-LewisX (SLeX) or the individual carbohydrates fucose, galactose, and sialic acids mimicking the complex SLeX binding motive. The glycopolymers strongly bind to primary human macrophages, without activating them, and also to primary human blood leukocytes, but poorly to fibroblasts and endothelial cells in vitro. After intravenous injection in mice, all glycopolymers accumulated in the liver without causing hepatotoxicity. The glycosylated binder most potently targeted resident hepatic macrophages (Kupffer cells) and protected mice from acute toxic liver injury in the two different experimental models, carbon tetrachloride (CCl4) or Concanavalin A (ConA)-based hepatitis. Its sulfated counterpart, on the other hand, induced a decrease in infiltrating and resident macrophages, increased T helper cells, and aggravated immune-mediated liver injury. We demonstrate that, in the context of selectin-binding glycopolymers, minor modifications strongly impact leukocyte influx and macrophage activation, thereby ameliorating or aggravating liver inflammation depending on the underlying immunopathology. The nonsulfated random glycopolymer is a promising candidate for the treatment of inflammatory disease. The modulation of hepatic immune cells by selectin-binding glycopolymers might breach the immunosuppressive hepatic microenvironment and could improve efficacy of immunotherapies for inflammatory disease and cancer.

Analyzing the surface properties of acrylic-based water-soluble polymers

ABSTRACTThe surface properties of newly synthesized N-methoxy isopropyl acrylamide, N-methoxy isopropyl methacrylamide, cyclo propyl acrylamide, and cyclo propyl methacrylamide polymers were investigated using inverse gas chromatography. The highest dispersive component of the surface energy value was obtained for cyclo propyl methacrylamide at 30°C. The values obtained for all polymers were decreasing with the increasing temperature. The values obtained for the acidic and the basic parameters revealed strong basic characters for the surface of N-methoxy isopropyl methacrylamide and cyclo propyl methacrylamide polymers and weak basic characters for the surface of N-methoxy isopropyl acrylamide and cyclo propyl acrylamide polymers.

Efficient Tumor Accumulation, Penetration and Tumor Growth Inhibition Achieved by Polymer Therapeutics: The Effect of Polymer Architectures.

To obtain high tumor-specific accumulation, strong tumor penetration and low off-target uptake, we developed a series of polymer therapeutics with different architectures, including random, block, and brush-like structure, based on the classic N-(2-hydroxypropyl) methacrylamide polymers. The influence of polymer architecture on biological properties such as cellular uptake, blood clearance, and biodistribution have been investigated. Besides small micelles whose sizes were determined by polymer architectures, large aggregates formed by micelle aggregation could also be observed. Although they had different architectures, the drug release rate, endocytic pathways and cellular uptake level of various conjugates have been proved to be identical. The polymer architecture of various conjugates lay great impact on the blood clearance, biodistribution and tumor growth inhibition. We assumed that the differences in in vivo biological properties were coordinately caused by the different size of the small aggregates and the formation and stability of large aggregates for different conjugates. Even though the reason was still unclear, the results inspired us that only by diblock conjugates with improved cellular uptake can we realize tumor specific accumulation, deep penetration, and efficient tumor inhibition.

Abstract 14013: E-selectin-targeted Novel Nano Polymers Stabilize Atherosclerotic Plaque and Improve Cardiac Remodeling

Introduction: Inflammation is implicated in the initiation and progression of cardiovascular disease. Endothelial activation with up-regulation of E-selectin adhesion molecules stimulates leukocyte infiltration leading to atherosclerotic plaque growth, plaque vulnerability and acute myocardial infarction. Hypothesis: Novel E-selectin-targeted polymers, with or without dexamethasone, can prevent plaque progression and adverse cardiac remodeling in atherosclerosis prone ApoE deficient ApoE (-/-) mice. Methods and Results: To target and modulate cardiovascular inflammation we used novel N-(2-hydroxypropyl)-meth-acrylamide polymers conjugated with peptides that bind E-selectin with high affinity, with and without dexamethasone 1mg/kg (P-ESBP-Dex, P-ESBP). Five-month-old ApoE (-/-) mice were fed a high-fat diet (HFD) for 8 weeks. Plaque growth was assessed by vascular ultrasound (US) 4 and 8 weeks after onset of HFD. We used a novel software application designed to measure in-vivo vessel wall anatomy and motion in small-animal models. Following the baseline vascular US, mice were randomized to 4 treatment groups: P-ESBP-Dex, P-ESBP, free dexamethasone or saline, delivered by 4 weekly intraperitoneal injections. Left ventricular remodeling and function were assessed by echocardiography in parallel to the vascular US. We found that both P-ESBP and P-ESBP-Dex selectively targeted atherosclerotic lesions, and reduced wall thickness of the ascending aorta. Furthermore, compared with saline controls, P-ESBP significantly decreased the area of necrotic core in the aortic plaques (74.2±5.9 mm2 vs. 34.7±15.5 mm2, p<0.05). Notably, the addition of dexamethasone to P-ESBP did not improve their therapeutic effect. Finally, P-ESBP attenuated left ventricular diastolic and systolic dilatation, compared with controls. Conclusion: E-selectin binding polymers reduce the growth of atherosclerotic lesions, contribute to plaque stability and prevent adverse cardiac remodeling in ApoE (-/-) mice. We suggest a novel nanomedicine-based therapy for atherosclerosis, unstable plaque, and to prevent adverse cardiac remodeling.

Hybrid polymeric hydrogels via peptide nucleic acid (PNA)/DNA complexation

This work presents a new concept in hybrid hydrogel design. Synthetic water-soluble N-(2-hydroxypropyl)methacrylamide (HPMA) polymers grafted with multiple peptide nucleic acids (PNAs) are crosslinked upon addition of the linker DNA. The self-assembly is mediated by the PNA–DNA complexation, which results in the formation of hydrophilic polymer networks. We show that the hydrogels can be produced through two different types of complexations. Type I hydrogel is formed via the PNA/DNA double-helix hybridization. Type II hydrogel utilizes a unique “P-form” oligonucleotide triple-helix that comprises two PNA sequences and one DNA. Microrheology studies confirm the respective gelation processes and disclose a higher critical gelation concentration for the type I gel when compared to the type II design. Scanning electron microscopy reveals the interconnected microporous structure of both types of hydrogels. Type I double-helix hydrogel exhibits larger pore sizes than type II triple-helix gel. The latter apparently contains denser structure and displays greater elasticity as well. The designed hybrid hydrogels have potential as novel biomaterials for pharmaceutical and biomedical applications.

A deeper insight into the postpolymerization modification of polypenta fluorophenyl methacrylates to poly(n-(2-hydroxypropyl) methacrylamide).

This work provides a detailed insight into the synthesis of N-(2-hydroxypropyl)methacrylamide (HPMA) polymers employing the activated ester approach. In this approach, polypenta fluorophenyl methacrylate (PFPMA)-activated ester polymers are synthesized by the reversible addition-fragmentation chain transfer (RAFT) polymerization and transferred into HPMA-based systems by the use of 2-hydroxypropylamine. To prove quantitative conversion in the absence of side reactions, special attention is devoted to investigate different reaction conditions by different analytical methods ((1) H, (19) F, inverse-gated (13) C NMR, and zeta potential measurements). Furthermore the influence of common solvent impurities, such as water, is investigated. Besides differences in polymer tacticity, the poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA) synthesized under water-free conditions display the same properties like the conventional synthesized control-PHPMA. However, 3% water content in the dimethylsulfoxide are already sufficient to yield PHPMA polymers with a negative zeta potential of -15.8 mV indication the presence of carboxylic groups due to partial hydrolysis of the activated ester.

All-atom molecular dynamics simulation of HPMA polymers

Structural properties such as size, shape and density distribution of a range of N-(2-hydroxypropyl)methacrylamide (HPMA) polymers in various solvent models have been investigated. Common atomistic force fields were compared against rotational barriers and relative conformational energies obtained from ab initio and density functional theory (DFT) data for a monomer and dimer of HPMA. This identified the AMBER99 parameter set as the most appropriate for representing the structures and so AMBER99 was employed for all molecular dynamics simulations. MD trajectories were calculated for a range of polymer sizes from 4 to 265 repeat units (2 to 35 kDa). The time averaged radius of gyration was extracted from trajectories and interpreted in the context of Flory's mean field approach. Comparison with data obtained from small angle neutron scattering (SANS) experiments was then used to differentiate between alternative solvent models. The shape adopted by such polymers was evaluated by fitting structures to ellipsoids, to allow separate analysis of radius and density profile along each axis. The density distribution of atoms was defined using these ellipsoids according to centre of mass or centre of neutron scattering lengths, the latter allowing direct comparison with experimental SANS data. We show that computational simulation of such polymers has practical application in obtaining detailed morphological information of polymer solution structure, and as a benchmark for coarse-grained methods.

Guanidine-Containing Methacrylamide (Co)polymers via aRAFT: Toward a Cell-Penetrating Peptide Mimic

We report the synthesis and controlled radical homo- and block copolymerization of 3-guanidinopropyl methacrylamide (GPMA) utilizing aqueous reversible addition-fragmentation chain transfer (aRAFT) polymerization. The resulting homopolymer and block copolymer with N-(2-hydroxypropyl) methacrylamide (HPMA) were prepared to mimic the behavior of cell penetrating peptides (CPPs) and poly(arginine) (> 6 units) which have been shown to cross cell membranes. The homopolymerization mediated by 4-cyano-4-(ethylsulfanylthiocarbonylsulfanyl)pentanoic acid (CEP) in aqueous buffer exhibited pseudo-first-order kinetics and linear growth of molecular weight with conversion. Retention of the "living" thiocarbonylthio ω-end-group was demonstrated through successful chain extension of the GPMA macroCTA yielding GPMA(37)-b-GPMA(61) (M(w)/M(n) =1.05). Block copolymers of GPMA with the non-immunogenic, biocompatible HPMA were synthesized yielding HPMA(271)-b-GPMA(13) (M(w)/M(n) = 1.15). Notably, intracellular uptake was confirmed by fluorescence microscopy, confocal laser scanning microscopy, and flow cytometry experiments after 2.5 h incubation with KB cells at 4 °C and at 37 °C utilizing FITC-labeled, GPMA-containing copolymers. The observed facility of cellular uptake and the structural control afforded by aRAFT polymerization suggest significant potential for these synthetic (co)polymers as drug delivery vehicles in targeted therapies.

Temperature responsive methacrylamide polymers with antibacterial activity

A new methacrylamide monomer, hexylamine methacrylamide (MAHA), was synthesized and used in polymerizations. The homopolymer of MAHA and its copolymers were synthesized by free radical polymerization techniques with N-isopropyl acrylamide (NIPAAm) in two different compositions. The quaternization of the homopolymer and copolymers were carried out using 1-bromopropane. The copolymers with NIPAAm and a low MAHA content showed temperature-responsive behavior in an aqueous environment. The lower critical solution temperatures (LCSTs) of these polymers varied between 32°C and 44°C. The LCSTs of quaternized copolymers were higher than those of neutral copolymers because they were more hydrophilic. The obtained homopolymers and copolymers were tested for antibacterial activities against S. aureus and E. coli. The quaternized water-soluble copolymers showed antibacterial activities against S. aureus. The quaternization resulted in the synthesis of both antibacterial and temperature-responsive copolymers.

Facile synthesis of controlled‐structure primary amine‐based methacrylamide polymers via the reversible addition‐fragmentation chain transfer process

AbstractWe report here a novel direct method for the syntheses of primary aminoalkyl methacrylamides that requires mild reagents and no protecting group chemistry. The reversible addition‐fragmentation chain transfer polymerization (RAFT) of the aminoalkyl methacrylamide revealed to be highly efficient with 4‐cyanopentanoic acid dithiobenzoate (CTP) as chain transfer agent and 4,4′‐azobis(4‐cyanovaleric acid) (ACVA) as initiator. Cationic amino‐based homopolymers of reasonably narrow polydispersities (Mw/Mn < 1.30) and predetermined molecular weights were obtained without recourse to any protecting group chemistry. A range of block and random copolymers were also synthesized via the RAFT process. The homopolymers and copolymers were characterized by aqueous conventional and triple detection gel permeation chromatography systems. Furthermore, the primary amine‐based methacrylamide monomers and polymers revealed to be highly stable both with the primary amino group in the protonated and deprotonated form. We have also demonstrated that stabilized gold nanoparticles can be generated with the RAFT‐synthesized amine‐based polymers via a photochemical process. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4984–4996, 2008

Biodegradable, Cationic Methacrylamide-Based Polymers for Gene Delivery to Ovarian Cancer Cells in Mice

A series of cationic, methacrylamide polymers was tested for use as a biodegradable gene carrier in ovarian cancer. Tumor transfection activity of polyplexes consisting of a reporter gene and different methacrylamide polymers was assessed, after intraperitoneal injection in mice bearing an ovarian cancer xenograft. In this model, polyplexes based on poly(HPMA-DMAE) showed transfection activity similar to polyplexes based on the nondegradable and rather toxic polyethylenimine (PEI22). The tumor transfection activity of the pHPMA-DMAE polyplexes was remarkable considering their poor transfection activity in in vitro assays. Polyplexes based on pHPMA-DMAE were devoid of any cytotoxicity and mediated highest transfection activity at the highest N/P ratio investigated. Tumor cell gene expression after a single administration of these polyplexes rapidly declined within time, at a similar rate to that observed after injection with polyplexes based on PEI22. Incubation of the polyplexes with hyaluronic acid (HA), a polyanion accumulating in the ascitic fluid of ovarian cancer bearing mice, changed the physical characteristics of the pHPMA-DMAE and PEI22 polyplexes. The transfection activity of PEI22-based polyplexes, but not that of pHPMA-DMAE based polyplexes, was strongly impaired by HA. Differences in HA sensitivity might have contributed to the in vivo gene expression activities of pHPMA-DMAE- and PEI22-based polyplexes. pHPMA-DMAE-based polyplexes have potential for use in ovarian cancer therapy due to their considerable transfection activity, their low cytotoxicity, and their HA resistance.

Synthesis and Characterization of Antibacterial and Temperature Responsive Methacrylamide Polymers

A new methacrylamide monomer (MAMP) containing a pyridine moiety was synthesized by reacting methacrylic anhydride and 3-(aminomethyl) pyridine. The monomer was homopolymerized in 1,4-dioxane and copolymerized with N-isopropyl acrylamide in DMF at two different compositions using AIBN as an initiator. The pyridine groups of the homopolymer and copolymers were reacted with various bromoalkanes containing 12, 14, and 16 carbon alkyl chains to obtain the polymers with pendant pyridinium groups. The monomer and polymers were characterized by elemental analysis, NMR, FTIR, SEC, TGA, and DSC. The neutral and quaternized copolymers with low MAMP content were water-soluble and showed temperature-responsive behavior in aqueous solutions. The lower critical solution temperatures (LCSTs) of these polymers varied between the temperatures of 25 and 42 °C. The LCST of quaternized copolymers were higher than that of the neutral copolymer because they were more hydrophilic. The LCST of the quaternized copolymers decreased with an increase in the alkyl chain length on the pyridinium group because the copolymers became more hydrophobic this way. The antibacterial activities of water-soluble copolymers were investigated against Staphylococcus aureus and Escherichia coli using the broth dilution and spread plate methods, whereas the water-insoluble polymers were tested for the antibacterial activity against the same types of bacteria using the shaking flask method. The quaternized water-soluble copolymers showed excellent antibacterial activities against both types of bacteria, whereas the neutral polymers and quaternized water-insoluble homopolymers and copolymers were not active.

Methacrylamide Polymers with Hydrolysis-Sensitive Cationic Side Groups as Degradable Gene Carriers

Water-soluble polymers with hydrolyzable cationic side groups (structure of the monomers are shown in Figure 1) were synthesized and evaluated as DNA delivery systems. The polymers, except for pHPMA-NHEM, were able to condense plasmid DNA into positively charged nanosized particles. The rate of hydrolysis at 37 degrees C and pH 7.4 of the side groups differed widely; the fastest rate of hydrolysis was observed for HPMA-DEAE (half-life of 2 h), while HPMA-DMAPr had the lowest rate of hydrolysis (half-life of 70 h). In line with this, pHPMA-DEAE-based polyplexes showed the fastest destabilization of the polyplexes at 37 degrees C and pH 7.4. Polyplexes based on pHPMA-DEAE, pHPMA-DMAE, and pHPMA-MPPM showed release of intact DNA within 24, 48, and 48 h, respectively, after incubation at 37 degrees C and pH 7.4. PHPMA-DEAE and pHPMA-MPPM based polyplexes showed the highest transfection activity (almost twice as active as pEI). Importantly, the pHPMA-DEAE, pHPMA-MPPM, and pHPMA-BDMPAP polyplexes preserved their transfection activity in the presence of serum proteins. All polymers investigated showed a substantial lower in vitro cytotoxicity than pEI. In conclusion, pHPMA-based polyplexes are an attractive class of biodegradable vectors for nonviral gene delivery.

Tailoring of Stimuli-Responsive Water Soluble Acrylamide and Methacrylamide Polymers

The tailoring of the lower critical solution temperature (LCST) polymers of acrylamide and methacrylamide in water is achieved by chemical modification of freely water soluble precursor polymers poly[N-2-hydroxypropylmethacrylamide], poly[N,N-bis(hydroxyethyl)acrylamide] and poly[N-{tris(hydroxymethyl)methyl}acrylamide]. Two principal reactions, namely acetylation and cinnamoylation, are applied. By varying the acylating agent as well as the extent of acylation, the LCST can be tailored easily. The cloud points observed for the different polymer series do not correlate with the apparent hydrophilicity of the parent polymers according to the content of hydroxyl groups. The results thus exemplify the difficulties to predict the behaviour of modified thermosensitive polymers by simply analysing the balance of hydrophilic to hydrophobic molecular fragments. Chemical modification by cinnamoylation provides photoreactive copolymers e.g susceptible to photocrosslinking. When the polymers are prepared by polymerization using a disulfide-functionalized azo-initiator, efficient grafting of the modified copolymers on gold surfaces is possible to prepare ultrathin hydrogel films, as demonstrated by Surface Plasmon Resonance.