Synthetic Water-soluble Polymers Research Articles

The influence of poly- N-[(2,2-dimethyl-1,3-dioxolane)methyl]acrylamide on fibrin polymerization, cross-linking and clot structure

Poly- N-[(2,2-dimethyl-1,3-dioxolane)methyl]acrylamide (PDMDOMA) is a neutral synthetic water-soluble polymer. In this report, we evaluated the influence of PDMDOMA on blood hemostasis by studying the fibrin polymerization process, the three-dimensional clot structure, and the mechanical properties and fibrinolysis. PDMDOMA altered the normal fibrin polymerization by changing the rate of protofibril aggregation and resulting in a 5-fold increase in the overall turbidity. Fibrin clots formed in presence of PDMDOMA exhibited thinner fibers with less branching which resulted in a more porous and heterogeneous clot structure in scanning electron micrographs. The overall strength and rigidity of the whole blood clot also decreased up to 10-fold. When a combination of plasminogen and tissue-plasminogen activators were included in clotting reactions, fibrin clots formed in the presence of PDMDOMA exhibited highly shortened clot lysis times and was supported by the enhanced clot lysis measured by thromboelastography in whole blood. Further evidence of the altered clot structure and clot cross-linking was obtained from the significant decrease in d-dimer levels measured from degraded plasma clot. Thus, PDMDOMA may play an important role as an antithrombotic agent useful in prophylactic treatments for thrombosis by modulating fibrin clot structure to enhance fibrinolysis.

Modification of papermaking grade fillers: A brief review

The use of fillers in paper products can provide cost and energy savings, improved paper properties, increased productivities, and specifically desired paper functionalities. There are many problems associated with the use of fillers, such as unsuitability of calcium carbonate fillers in acid papermaking, negative effects of filler loading on paper strength, sizing, and retention, and tendencies of fillers to cause abrasion and dusting. In order to solve these problems and to make better use of fillers, many methods have been proposed, among which filler modification has been a hot topic. The available technologies of filler modification mainly include modification with inorganic substances, modification with natural polymers or their derivatives, modification with water-soluble synthetic polymers, modification with surfactants, modification with polymer latexes, hydrophobic modification, cationic modification, surface nano-structuring, physical modification by compressing, calcination or grinding, and modification for use in functional papers. The methods of filler modification can provide improved acid tolerant and optical properties of fillers, enhanced fiber-filler bonding, improved filler retention and filler sizabilities, alleviated filler abrasiveness, improved filler dispersability, and functionalization of filled papers. Filler modification has been an indispensable way to accelerate the development of high filler technology in papermaking, which is likely to create additional benefits to papermaking industry in the future.

Synthetic Melanins with Antiviral Activity

Enveloped viruses can cause severe, and occasionally life‐threatening, infections in humans and animals. We have prepared a family of water‐soluble synthetic melanin polymers that have differing physicochemical properties and distinctive selectivities for preventing the infection of animal cells by enveloped viruses in vitro. For example, our series of 20 compounds with anti‐HIV activity have been shown to have ED50's in the range of 4 to 216 ng/mL (http://www.bioactivepolymers.com ). Recently we submitted 10 synthetic melanins to the NIAID's Antimicrobial Acquisition and Coordinating Facility for in vitro activity testing against 7 herpesviruses, 7 respiratory viruses, 2 orthopoxviruses, and 10 bioterrorism viruses. The compounds were tested for inhibitory activity using the NIAID's standard screening screening assays as described on their website (http://niaid‐aacf.org/screeningassays.htm ). The results showed that the most potent of our synthetic compounds had the following ED50's (μg/mL) for the 20 viruses tested thus far: HSV1, 1.4; HSV2, 0.06; CMV, 3.4; VZV, < 0.03; EBV, 98; Dengue C., 26; Rift Valley Fever, 26; Tacribe, 41; RSV A., 32; Cowpox, 27; Vaccinia, 10; SARS, 13; H1N1, 2.5; H3N2, 3.2; H5N1, 0 .21; Flu B, 2.0. ED50's of > 100 μg/mL were observed for Yellow Fever, Adenovirus, PIV, and Rhinovirus. The inhibitory activities of screen‐positive compounds with moderate to high activities were confirmed by supplementary testing. The compounds typically had low toxicities toward animal cells, with CC50's of >100 μg/mL. The results suggest that synthetic melanins are promising candidates for the development of topical microbicides for use in the prevention of STD's and for use in the prevention and treatment of other viral infections in humans and animals.

Kinetic methods for determining water-soluble polymers

The effect of synthetic water-soluble polymers on the reactions of hydroquinone or 3,3′,5,5′-tetramethylbenzidine periodate oxidation with hydrogen peroxide is studied. A polymer solution was introduced into the reaction and a change in its rate was detected by photometry. Possible reasons for the effect of polymers are discussed, the role of the positive and negative charges of the polymeric chain and the nature of the indicator reaction are considered. The possibility of determining polyelectrolytes by their accelerating and inhibiting effect is demonstrated, including that, under the conditions of polyelectrolyte complex formation, and also by binding with a metal ion catalyzing the indicator reaction. Procedures are proposed for the simple and rapid determination of 3,6-ionene, polyanetholesulfonic acid, polyhexamethyleneguanidine (∼10−5 to 10−4 M, in terms of the monomer), polyethyleneimine and chitosans (∼10−7−10−6 M in terms of the monomer) in aqueous solutions, and also of polyethyleneimine by carrying out the indicator reaction on a silica surface (4 × 10−6 to 0.7 M in terms of the monomer).

Small-angle neutron scattering from typical synthetic and biopolymer solutions

Small-angle neutron scattering (SANS) has been used to investigate the solution properties of four model polymers, two poly-amino acids (poly(lysine) and poly (proline)), and two water-soluble synthetic polymers (poly (acrylic acid) and poly(ethylene oxide)). In each case, one of the two polymers is charged, while the other is neutral. SANS measurements were made in the semi-dilute con- centration regime in two different solvents (d-water and d- ethylene glycol). The scattering signals were decomposed into low-Q clustering and high-Q solvation contributions. The temperature dependence of the scattering parameters was determined for poly(lysine) and poly(ethylene oxide) solutions over the temperature range of 13 to 82 °C. Analysis of the SANS spectra revealed that with increasing temper- ature, the solvation intensity increased in both solvents, while the clustering intensity increased in d-water and decreased in d-ethylene glycol. Significant differences were observed between the SANS spectra of charged and neutral polymer solutions. However, biopolymers and synthetic polymers exhibited qualitatively similar behavior.

Foam-like materials produced from abundant natural resources

Low density polymer/clay aerogel composites were prepared using casein and sodium montmorillonite clay (Na+-MMT). The use of naturally occurring polymers allows for the creation of environmentally friendly/benign materials. Using a freeze drying process, composites were made that have densities in the range of 0.08–0.15 g cm−3 and exhibit properties similar to typical foamed polymers such as expanded polystyrene and rigid polyurethane foams. It was found that a minimum of at least 5wt% casein is required in the initial aqueous mixture in order to create a viable structure. The casein-containing materials created using this freeze drying process are similar to those previously produced with synthetic water soluble polymers such as poly(vinyl alcohol) but exhibit superior mechanical properties when compared to any synthetic polymer/clay aerogel composite tested to date.

Synthesis and Evaluation of Water-Soluble Poly(vinyl alcohol)-paclitaxel Conjugate as a Macromolecular Prodrug

Paclitaxel (PTX) is an antitumor agent for the treatment of various human cancers. Cremophor EL and ethanol are used to formulate PTX in commercial injection solutions, because of its poor solubility in water. However, these agents cause severe allergic reaction upon intravenous administration. The aim of this study is to synthesize water-soluble macromolecular prodrugs of PTX for enhancing the therapeutic efficacy. Poly(vinyl alcohol) (PVA, 80 kDa), water-soluble synthetic polymer, was used as a drug carrier which is safe and stable in the body. The 2'-hydroxyl group of PTX was reacted with succinic anhydride and then carboxylic group of the succinyl spacer was coupled to PVA via ethylene diamine spacer, resulting the water-soluble prodrug of poly(vinyl alcohol)-paclitaxel conjugate (PVA-SPTX). The solubility of PTX was greatly enhanced by the conjugation to PVA. The release of PTX from the conjugate was accelerated at the neutral to basic conditions in in vitro release experiment. [125 I]-labeled PVA-SPTX was retained in the blood circulation for several days and was gradually distributed into the tumorous tissue after intravenous injection to the tumor-bearing mice. PVA-SPTX inhibited the growth of sarcoma 180 cells subcutaneously inoculated in mice. It was suggested that the water-solubility of PTX was markedly enhanced by the conjugation to PVA, and PVA-SPTX effectively delivered PTX to the tumorous tissue due to the enhanced permeability and retention (EPR) effect.

廃水処理に用いられる高分子凝集剤

Various synthetic water-soluble polymers are used for flocculation and dewatering treatments of waste water.

Novel Biocompatible Cationic Copolymers Based on Polyaspartylhydrazide Being Potent as Gene Vector on Tumor Cells

The reaction between alpha,beta-poly(aspartylhydrazide) (PAHy), a water soluble synthetic polymer and 3-(carboxypropyl)trimethyl-ammonium chloride (CPTACl) produced copolymers bearing permanent positive charges (PAHy-CPTA) with molecular weight of 10 kDa and PAHy-CPTA copolymers differing in positive charge amount (18-58%) were chosen for biological investigations. Biophysical properties of DNA/PAHy-CPTA polyplexes were evaluated in terms of DNA condensation, zeta potential and size distribution. Cytotoxicity studies on Neuro2A murine neuroblastoma cells evidenced absence of toxicity of these copolymers up to 300 microg/ml unlike linear polyethylenimine (LPEI) that was highly toxic already at 20 microg/ml. PAHy-CPTA copolymers did not induce any erythrocyte aggregation up to 1 mg/ml. Cellular interaction studies of PAHy-CPTA polyplexes evidenced a faster binding of these polyplexes with cells compared to DNA/LPEI polyplexes. The in vitro transfection ability of PAHy-CPTA polyplexes was strongly affected by experimental conditions reaching about 10% of the transfection efficiency of optimized LPEI polyplexes. Finally, in vivo application studies confirmed the biocompatibility of PAHy-CPTA copolymers. With LPEI, clear signs of microvesicular fatty liver were observed and with LPEI polyplexes significant weight loss. In strong contrast, PAHy-CPTA did not induce histopathological changes or weight loss.

Designing polymer conjugates as lysosomotropic nanomedicines

Marriage of cell biology (the concept of 'lysosomotropic drug delivery') and the realization that water-soluble synthetic polymers might provide an ideal platform for targeted drug delivery led to the first synthetic polymer-drug conjugates that entered clinical trials as anticancer agents. Conceptually, polymer conjugates share many features with other macromolecular drugs, but they have the added advantage of the versatility of synthetic chemistry that allows tailoring of molecular mass and addition of biomimetic features. Conjugate characteristics must be optimized carefully to ensure that the polymeric carrier is biocompatible and that the polymer molecular mass enables tumour-selective targeting followed by endocytic internalization. The polymer-drug linker must be stable in transit, but be degraded at an optimal rate intracellularly to liberate active drug. Our early studies designed two HPMA [N-(2-hydroxypropyl)methacrylamide] copolymer conjugates containing doxorubicin that became the first synthetic polymer-drug conjugates to be tested in phase I/II clinical trials. Since, a further four HPMA copolymer-anticancer drug conjugates (most recently polymer platinates) and the first polymer-based gamma-camera imaging agents followed. Polymer-drug linkers cleaved by lysosomal thiol-dependent proteases and the reduced pH of endosomes and lysosomes have been used widely to facilitate drug liberation. It is becoming clear that inappropriate trafficking and/or malfunction of enzymatic activation can lead to new mechanisms of clinical resistance. Recent studies have described HPMA copolymer conjugates carrying a combination of both endocrine and chemotherapy that are markedly more active than individual conjugates carrying a single drug. Moreover, current research is investigating novel dendritic polymer architectures and novel biodegradable polymers as drug carriers that will provide improved drug delivery and imaging probes in the future. The present paper reviews the clinical status of polymeric anticancer agents, the rationale for the design of polymer therapeutics and discusses the benefits and challenges of lysosomotropic delivery.

Electroplating of chromium coatings from Cr(III)-based electrolytes containing water soluble polymer

The effect of certain water-soluble synthetic polymers on the current efficiency, the kinetics of partial cathodic reactions, and certain properties of coatings at the chrome plating from sulfate-formate baths based on Cr(III) salts is studied. A polymeric additive of the nonionogenic type N1 (3 × 106 g/mol) is proposed, which favors the deposition of chromium coatings that have good adhesion to the surface, do not crack, and have a thickness of several tens micrometers. It is found that the polymers have an accelerating effect on the aggregation of the particles of the chromium-hydroxide sol formed in the near-electrode layer, which, apparently, improves the deposit quality and enhances the current efficiency. It is shown that the resulting amorphous-crystalline chromium deposits are sufficiently hard and exhibit good protectiven ability at the anodic dissolution in aggressive media.

The Denaturation Transition of DNA in Mixed Solvents

The helix-to-coil denaturation transition in DNA has been investigated in mixed solvents at high concentration using ultraviolet light absorption spectroscopy and small-angle neutron scattering. Two solvents have been used: water and ethylene glycol. The “melting” transition temperature was found to be 94°C for 4% mass fraction DNA/d-water and 38°C for 4% mass fraction DNA/d-ethylene glycol. The DNA melting transition temperature was found to vary linearly with the solvent fraction in the mixed solvents case. Deuterated solvents (d-water and d-ethylene glycol) were used to enhance the small-angle neutron scattering signal and 0.1M NaCl (or 0.0058 g/g mass fraction) salt concentration was added to screen charge interactions in all cases. DNA structural information was obtained by small-angle neutron scattering, including a correlation length characteristic of the inter-distance between the hydrogen-containing (desoxyribose sugar-amine base) groups. This correlation length was found to increase from 8.5 to 12.3 Å across the melting transition. Ethylene glycol and water mixed solvents were found to mix randomly in the solvation region in the helix phase, but nonideal solvent mixing was found in the melted coil phase. In the coil phase, solvent mixtures are more effective solvating agents than either of the individual solvents. Once melted, DNA coils behave like swollen water-soluble synthetic polymer chains.

Two-dimensional classification of amphiphilic monomers based on interfacial and partitioning properties. 1. Monomers of synthetic water-soluble polymers

A classification of amphiphilic monomers based on the interfacial and partitioning properties has been proposed. Monomers partitioned at equilibrium between two immiscible phases were ascribed with a pair of parameters: standard free energy of adsorption at the interface and standard free energy of partition between the two phases. These two parameters are represented in a form of two-dimensional diagram (both of them being normalized by kT factor). Comparison of the parameters in question gives information on energetic preferences of the molecules to be located at the interface or in the bulk phases. Four monomers of synthetic water-soluble polymers, namely, N-isopropylacrylamide, 1-vinylimidazole, N-vinylpyrrolidone and N-vinylcaprolactam have been classified according to the above method at various temperatures. The possibility to extend the classification to arbitrary chemicals is discussed.

Reversibly stable thiopolyplexes for intracellular delivery of genes

Novel polyaspartamide non-viral carriers for gene therapy were synthesized by introducing, on the same polymer backbone, positively charged groups, for electrostatic interactions with DNA, and thiol groups for the formation of disulfide bridges between polymer chains. The introduction of thiols was aimed to have a vector with low redox potential sensitivity: disulfide crosslinking in fact, being stable in extracellular environment, allowed either to have stable complexes in plasma, that can protect DNA from metabolism, or to be reduced inside the cell, where the excess of glutathion in reduced form maintains a low redox potential. The consequent destabilization of the complex after disulfide cleavage can release DNA selectively inside the cells. α,β-poly( N-2-hydroxyethyl)- d, l-aspartamide (PHEA) was used as starting polymer being a highly water-soluble synthetic polymer, already proposed with success as therapeutic carrier by our group. In this study, PHEA was firstly functionalised with ethylendiamine, obtaining a well defined copolymer with pendant primary amine groups (PHEA-EDA), to which N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) and 3-(carboxypropyl)trimethyl-ammonium chloride (CPTA) were linked in two subsequent steps, allowing the introduction of thiol and cationic groups respectively. Finally DTT treatment lead to the final PHEA-EDA-SH-CPTA thiopolycation, named PESC. The present work describes the synthesis and characterization of the thiopolycation PESC. 1H NMR spectroscopy detected the derivatization molar degrees in SPDP and CPTA; the formation of DNA complexes (thiopolyplexes), their stability in the presence of polyanions and the ability to release DNA under reductive conditions were studied by agarose gel electrophoresis. DNase II degradation study was carried out to detect the ability of thiopolyplex to stabilize DNA towards enzymatic metabolism. Thiopolyplexes were then characterized by Dynamic Light Scattering (DLS) and Zeta Potential analysis. Finally, in vitro toxicity profile (MTT) and gene transfer efficiency (Luciferase assay) were carried out to evaluate thiopolyplex biocompatibility, safety and efficacy to be used as gene delivery system.

Flocculants—an Ecofriendly Approach

Although water-soluble synthetic polymers find wide applications as flocculants, the potential problem associated with their use is lack of biodegradability and high cost. Polysaccharides owing to their distinctive features like ability to undergo different chemical reactions, biodegradability and sustainability inspire hope to obtain effective, economical viable and safe substitute of the synthetic flocculants. In this regard, chemical modification of Cassia tora and guar gum was carried out through different substitution and grafting reactions. The modified products were tested against kaolin under laboratory conditions vis-a-vis polyacrylamide based synthetic flocculant.

Direct electrochemistry of hemoglobin in PHEA and its catalysis to H2O2

Hemoglobin (Hb) was immobilized on glassy carbon (GC) electrode by a kind of synthetic water-soluble polymer, poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA). A pair of well-defined and quasi-reversible cyclic voltammetric peaks was achieved, which reflected the direct electron-transfer of the Fe(III)/Fe(II) couple of Hb. The formal potential (E degrees'), the apparent coverage (Gamma(*)) and the electron-transfer rate constant (k(s)) were calculated by integrating cyclic voltammograms experimental data. Scanning electron microscopy (SEM) demonstrated the morphology of Hb-PHEA film very different from the Hb and PHEA films. Ultraviolet visible (UV-vis) spectroscopy showed Hb in PHEA film remained its secondary structure similar to the native state. In respect that the immobilized protein remained its biocatalytic activity to the reduction of hydrogen peroxide (H(2)O(2)), a kind of mediator-free biosensor for H(2)O(2) could be developed. The apparent Michaelis-Menten constant (K(m)(app)) was estimated to be 18.05 microM. The biosensor exhibited rapid electrochemical response and good stability. Furthermore, uric acid (UA), ascorbic acid (AA) and dopamine (DA) had little interferences with the amperometric signal of H(2)O(2), which provide the perspective of this H(2)O(2) sensor to be used in biological environments.

Two-dimensional classification of amphiphilic monomers based on interfacial and partitioning properties. 1. Monomers of synthetic water-soluble polymers

Two-dimensional classification of amphiphilic monomers based on interfacial and partitioning properties. 1. Monomers of synthetic water-soluble polymers

Novel Cationic Copolymers of a Polyasparthylhydrazide: Synthesis and Characterization

α,β-poly(asparthylhydrazide) (PAHy), a water soluble synthetic polymer, was functionalized by using EDCI chemistry with 3-(carboxypropyl)trimethyl-ammonium chloride (CPTACl) obtaining carboxypropyltrimethyl ammonium copolymers (PAHy-CPTA). Three PAHy-CPTA copolymers at increasing derivatization degrees (38%, 48%, 58%) were chosen for subsequent investigations. The capability of these copolymers to bind, neutralize, and protect DNA against degradation by DNase II was evalued by gel retardation assay and DNA degradation test at pH 5.5. Zeta potential measurements show that all studied polymers are able to neutralize the anionic charge of DNA at polymer/DNA weight ratio in the range of 0.8/1–5/1. Polyplex dimensional distribution analyses in bistilled water, saline solution NaCl 0.9%, and HEPES pH 7 show that polyplex size is strongly affected by both presence and type of electrolyte and with time incubation.

Water Soluble Rigid Rod Polymers: A SANS Study of Shear-Induced Alignment and Relaxation

In this paper, we report the effect of shear and relaxation on low concentration solutions of a synthetic water-soluble rigid rod polymer in deuterated water using small angle neutron scattering (SANS). The polymer used is sulfo poly p-phenyleneterephtalamide (Sulfo-PPTA). At rest, a 1wt% solution of Sulfo-PPTA presents a scattering maximum at small angles that is related to the interaction between rods. Under the action of very small shear rates, a high alignment is observed. The scattering maximum, initially isotropic, strongly increases upon shear in the direction perpendicular to the applied shear while it is suppressed in the direction parallel to the shear. After cessation of shear the alignment remains for a considerable period of time. The ?P2? order parameter has been determined from the SANS data during application of shear and during relaxation. The formation of needle-like aggregates in solution is suggested as a possible explanation of our results.

Complex formation of protein with different water-soluble synthetic polymers.

The formation of protein-polymer complexes was studied in an aqueous system using dynamic light scattering (DLS) and static light scattering (SLS) as the main experimental tools. Human serum albumin (HSA) was used as a protein and complexed with four representative water-soluble polymers: poly(N-isopropylacrylamide) (PNIPA), poly(ethylene glycol) (PEG), poly(vinyl pyrrolidone) (PVP), and poly(vinyl alcohol) (PVA). The first three molecular weights were within 420,000-540,000 and the last one was 270,000. The complexation was performed at 25 degrees C in 0.01 M NaCl solution adjusted to pH 3 with HCl as a function of mixing ratio (rm; molar ratio of polymer to HSA). From SLS experiments, we determined the molecular weight of the resulting complexes, from the value of which the number (nb) of bound proteins per polymer was estimated. It was found that each polymer forms an intrapolymer complex over a wide range of rm (1.2 > or = rm > or = 0.01). Then, a marked decrease in nb with increasing rm was found. Over the whole rm range, the HSA-PNIPA complex exhibited a large nb value, as compared with the other three complexes whose nb values at the same rm were close to one another. Both the hydrodynamic radius (Rh) by DLS and the radius of gyration (Rg) by SLS for the complexes of PNIPA, PVP, and PVA decreased and then reached a constant value as nb decreased with increasing rm. In the PEG system, however, there were a few changes in Rh and Rg with nb. The Rg/Rh ratio, as an indication of chain expansion, was found to increase with decreasing nb in the PNIPA system. The complexes of PVA and PVP displayed a similar tendency, although the magnitude of the increasing trend was smaller than that of the PNIPA complex. In contrast, the Rg/Rh ratio of the PEG complex hardly varied depending on nb. These results were discussed in connection with the differences of physicochemical properties among four water-soluble polymers.