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Zika virus (ZIKV) is an emerging mosquito-borne pathogen associated with microcephaly and other congenital abnormalities in newborns as well as neurologic complications in adults. The explosive transmission of the virus in the last ten years put it in the limelight and improved our understanding of its biology and pathology. Currently, no vaccine or drugs are available to prevent or treat ZIKV infections. Knowing the potential of flaviviruses to broaden their geographic distribution, as observed for the West Nile virus, it is of importance to develop novel antiviral strategies. In this work, we identified poly(sodium 4-styrenesulfonate) (PSSNa) as a new polymeric ZIKV inhibitor. We demonstrated that PSSNa inhibits ZIKV replication in vitro both in animal and human cells, while no cytotoxicity is observed. Our mechanistic studies indicated that PSSNa acts mostly through direct binding to ZIKV particle and blocking its attachment to the host cells.

A series of poly(ethylene glycol)- block -poly(3-(methacryloylamino)propyl trimethylammonium chloride) (PEG- b -PMAPTAC) water-soluble block copolymers consisting of PEG and PMPTAC were obtained by reversible addition-fragmentation chain-transfer (RAFT) polymerization and demonstrated to function as highly effective herpes simplex virus type 1 (HSV-1) inhibitors as shown by in vitro tests (Vero E6 cells) and in vivo experiments (mouse model). Half-maximal inhibitory concentration (IC 50 ) values were determined by quantitative polymerase chain reaction to be 0.36 ± 0.08 μg/mL for the most effective polymer PEG 45 - b -PMAPTAC 52 and 0.84 ± 1.24 μg/mL for the less effective one, PEG 45 - b -PMAPTAC 74 . The study performed on the mouse model showed that the polymers protect mice from lethal infection. The polymers are not toxic to the primary human skin fibroblast cells up to the concentration of 100 μg/mL and to the Vero E6 cells up to 500 μg/mL. No systemic or topical toxicity was observed in vivo, even with mice treated with concentrated formulation (100 mg/mL). The mechanistic studies indicated that polymers interacted with the cell and blocked the formation of the entry/fusion complex. Physicochemical and biological properties of PEG x - b -PMAPTAC y make them promising drug candidates.

Di- and triblock copolymers with low dispersity of molecular weight were synthesized using radical addition-fragmentation chain transfer polymerization. The copolymers contained anionic poly(sodium 2-acrylamido-2-methylpropanesulfonate) (PAMPS) block as an anticoagulant component. The block added to lower the toxicity was either poly(ethylene glycol) (PEG) or poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC). The polymers prolonged clotting times both in vitro and in vivo. The influence of the polymer architecture and composition on the efficacy of anticoagulation and safety parameters was evaluated. The polymer with the optimal safety/efficacy profile was PEG47- b-PAMPS108, i.e., a block copolymer with the degrees of polymerization of PEG and PAMPS blocks equal to 47 and 108, respectively. The anticoagulant action of copolymers is probably mediated by antithrombin, but it differs from that of unfractionated heparin. PEG47- b-PAMPS108 also inhibited platelet aggregation in vitro and increased the prostacyclin production but had no antiplatelet properties in vivo. PEG47- b-PAMPS108 anticoagulant activity can be efficiently reversed with a copolymer of PEG and poly((3-(methacryloylamino)propyl)trimethylammonium chloride) (PMAPTAC) (PEG41- b-PMAPTAC53, HBC), which may be attributed to the formation of polyelectrolyte complexes with PEG shells without anticoagulant properties.

The parenteral anticoagulants may cause uncontrolled and life-threatening bleeding. Protamine, the only registered heparin antidote, is partially effective against low-molecular weight heparins, completely ineffective against fondaparinux and may cause unacceptable toxicity. Therefore, we aimed to develop a synthetic compound for safe and efficient neutralization of all parenteral anticoagulants. We synthesized pegylated PMAPTAC block copolymers, and then, we selected a lead heparin-binding copolymer (HBC). We assessed the effectiveness of HBC in the model of arterial thrombosis electrically induced in the carotid artery of rats by measuring thrombus weight, bleeding time, activated partial thromboplastin time, activated clotting time, and anti-factor Xa activity. The intravital tissue distribution, the cardiorespiratory, and organ toxicity were monitored. HBC diminished antithrombotic and anticoagulant effects of unfractionated heparin. Moreover, it stopped bleeding and completely reversed the enhancement of clotting times and anti-factor Xa activity caused by enoxaparin or fondaparinux. We observed slight pulmonary congestion and cell infiltration, but the cardiorespiratory parameters remained unchanged. We found a strong signal of fluorescently-labeled HBC in the urine, and a weaker in the liver and in the kidney. No signs of hepatic or nephrotoxicity were observed in the blood biochemistry or histopathologic examination. We developed a copolymer efficiently neutralizing effects of heparins in the living organism, which shows a very promising efficacy/safety profile and may help in the management of uncontrolled bleeding resulting from an anticoagulant injection. HBC could enable the safe replacement of unfractionated heparin with low-molecular weight heparins in patients undergoing cardiac surgery and complex vascular procedures., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Novel sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) and N-sulfonated chitosan (NSCH) have been synthesized, and their activity against influenza A and B viruses has been studied and compared with that of a series of carrageenans, marine polysaccharides of well-documented anti-influenza activity. NSPAHs were found to be nontoxic and very soluble in water, in contrast to gel-forming and thus generally poorly soluble carrageenans.In vitroandex vivostudies using susceptible cells (Madin-Darby canine kidney epithelial cells and fully differentiated human airway epithelial cultures) demonstrated the antiviral effectiveness of NSPAHs. The activity of NSPAHs was proportional to the molecular mass of the chain and the degree of substitution of amino groups with sulfonate groups. Mechanistic studies showed that the NSPAHs and carrageenans inhibit influenza A and B virus assembly in the cell., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Polyelectrolyte multilayers (PEMs) have found application in modifying material surfaces to make them adhesive or non-adhesive for animal cells. However, PEMs made of strong polyelectrolytes are not fully recognized in the literature. This study focuses on the interplay between the properties of PEM assembled from strong polyelectrolytes and cell adhesion and motility. Strong polycations (with quaternary ammonium groups) and a polyanion (with sulfonate groups) were obtained by modification of poly(allylamine hydrochloride) (PAH). Two types of multilayer films were assembled from these PAH derivatives and used to investigate the behavior of human skin fibroblasts (HSFs). The effect of surface charge, hydrophobicity, and film thickness on adhesion of HSFs in a serum-containing medium was studied with immunofluorescence microscopy. The results showed that adhesion of HSFs was strongly depended on the chemical functions of the terminal layer, whereas the wettability was not important. The surface of PEM can be strongly cytophobic (the quaternary ammonium terminal groups) or strongly cytophilic (the sulfonate terminal groups). Finally, the motile activity of HSFs seeded on glass coated with a varying number of polymer layers was investigated. It was demonstrated using an in vitro model that coating the substrate with only two polymer layers can considerably increase the average speed of HSFs movement and stimulate cell migration into the wound., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Protamine, the only registered antidote of unfractionated heparin (UFH), may produce a number of adverse effects, such as anaphylactic shock or serious hypotension. We aimed to develop an alternative UFH antidote as efficient as protamine, but safer and easier to produce. As a starting material, we have chosen generally non-toxic, biocompatible, widely available, inexpensive, and easy to functionalize polysaccharides. Our approach was to synthesize, purify and characterize cationic derivatives of dextran, hydroxypropylcellulose, pullulan and γ-cyclodextrin, then to screen them for potential heparin-reversal activity using an in vitro assay and finally examine efficacy and safety of the most active polymers in Wistar rat and BALB/c mouse models of experimentally induced arterial and venous thrombosis. Efficacy studies included the measurement of thrombus formation, activated partial thromboplastin time, bleeding time, and anti-factor Xa activity; safety studies included the measurement of hemodynamic, hematologic and immunologic parameters. Linear, high molecular weight dextran substituted with glycidyltrimethylammonium chloride groups at a ratio of 0.65 per glucose unit (Dex40-GTMAC3) is the most potent and the safest UFH inhibitor showing activity comparable to that of protamine while possessing lower immunogenicity. Cationic polysaccharides of various structures neutralize UFH. Dex40-GTMAC3 is a promising and potentially better UFH antidote than protamine.

Glucocorticoids (GCs) are broadly used in the treatment of inflammation and in suppressing hyperactivity of the immune system expressed in allergies, asthma, autoimmune diseases and sepsis. They are pleiotropic in nature, showing a wide range of diverse effects, including those which are harmful for the organism. Dexamethasone (DEX) is one of the most frequently used GCs and is considered as one of the safest. Still serious side-effects have been observed for this drug, mostly due to its hydrophobicity and low bioavailability. The potentially promising polymeric carrier systems to deliver DEX effectively are revised., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Photodynamic therapy (PDT) is a clinically approved method for treatment of cancer, microbial infections, and some other diseases. PDT has proved effective in the treatment of malignancies of various organs, including lung, bladder, gastrointestinal tract, and skin, and in the therapy of bacterial infection of skin wounds and carious lesions. It employs a combination of light and a drug (photosensitizer, PS) to induce phototoxicity against cancerous cells or bacteria. The efficiency of currently used PSs is limited due to their hydrophobic nature, which causes aggregation of the PS in aqueous media and low tumor selectivity (a low value of the tumor-to-normal tissue ratio). The purpose of this review is to present some aspects of the current state of knowledge on nanostructural carriers for the PS delivery. In this paper we reviewed studies on the development of nanostructural materials for PDT, especially those based on the polymeric and liposomal formulation of PS. We focused mainly on the nanostructural PSs obtained by the covalent attachment of hydrophilic polymer chain to the low-molecular-weight PS, the incorporation of PS into polymeric nanostructures such as micelles, and the solubilization of PS in liposome carriers.

The properties of heparin, a key anticoagulant, are reviewed. The important issues in heparinotherapy, i.e., reaching quick anticoagulant effect, maintaining therapeutic level of anticoagulation, heparin inhibition and non-invasive heparin formulations have been reviewed and discussed, with the focus on the role of polymeric substances in the proposed solutions.

A system of poly(ethylene glycol) bound tetraarylporphyrin entrapped in liposomal membranes was investigated. The interactions between the 5-(4-hydroxymethylphenyl)-10,15,20-tritolylporphyrin (Po) covalently attached to the poly(ethylene glycol) chain (PEG-Po), and phosphatidylcholine liposomes in the aqueous solution were studied. The adsorption of the investigated polymer to lipid vesicles was confirmed by measurements of dynamic light scattering and zeta potential. Experimental results demonstrate that the diameter of liposomes increased and the absolute value of the zeta potential decreased after addition of PEG-Po. The binding constants (K(b)) of Po chromophores to liposome in pH range from 5.2 to 9.0 were determined using fluorescence spectroscopy. The degree of binding was found to be pH-independent and the average value was 24.6 +/- 0.9 mg ml(-1). The acid-base properties of the porphyrin chromophores and their aggregation in an aqueous solution were also studied. pK values associated with imine-N protonation of the porphyrin core were found to be 2.59 and 0.68 at the ionic strength of 0.1 M. The equilibrium constant for dimerization, K(D), was found to be 5 x 10(3) M(-1).

Zika virus (ZIKV), belonging to the family of flaviviruses, is an emerging mosquito-borne pathogen causing microcephaly and other congenital abnormalities in newborns as well as various neurologic pathologies in adults. The climate change and the lifestyle of current societies, involving global mobility, result in a rapid broadening of ZIKV geographic distribution. There are no vaccines or drugs available to protect against or cure the diseases caused by that virus. Our in vitro studies have demonstrated that sodium polyanethole sulfonate (PASNa), a degradable polymer used in various biomedical applications, acts as an efficient ZIKV inhibitor, both in animal and human cells. The mechanistic studies indicated that PASNa bound to the ZIKV particles thus hindering their attachment to the host cells and also interfered in the late steps of viral replication. PASNa is characterized by very low cytotoxicity and its antiviral activity can be achieved at a concentration much lower than that at which its anticoagulant activity has to be considered. Isothermal titration calorimetry (ITC) studies have shown that the interaction of PASNa with human serum albumin (HSA), the most abundant blood protein, is the endothermic, entropydriven process resulting in the formation of stoichiometric (1:1) PASNa-HSA complexes with a hydrodynamic diameter of 8.8 ± 0.8 nm and zeta potential (ζ) equal to -21.3 mV. The analysis of CD spectra indicated that PASNa did not significantly affect the HSA secondary structure on binding to that protein. [ABSTRACT FROM AUTHOR]

Phenomena that occur between an insulin and four different positively charged polymers (protamine, cationic dextran, chitosan, and poliallylamine derivatives) were studied by dynamic light scattering and fluorescence measurements (using fluorescein-labeled polymers). These processes were compared to the reaction of polycations with heparin that is responsible for the neutralization of anticoagulant activity in blood stream.The nature of polycations interaction with heparin is electrostatic, while the interaction with insulin is more complicated.We observed that the presence of zinc atoms (and its complexing by nitrogen from macromolecules) is critical for insulin suspensions formation and stability. The differences between the nature of these two reactions were revealed. The highly immunogenic action of protamine present in long-acting insulin products makes it reasonable to develop similar systems based on the nonprotein polycations. [ABSTRACT FROM AUTHOR]

Human metapneumovirus (hMPV) is a widely distributed pathogen responsible for acute upper and lower respiratory infections of varying severity. Previously, we reported that N-sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) efficiently inhibit replication of the influenza virus in vitro and ex vivo. Here, we show a dose dependent inhibition of hMPV infection by NSPAHs in LLC-MK2 cells. The results showed strong antiviral properties of NSPAHs. While the activity of NSPAHs is comparable to those of carrageenans, they show better physicochemical properties and may be delivered at high concentrations. The functional assays showed that tested polymers block hMPV release from infected cells and, consequently, constrain virus spread. Moreover, further studies on viruses utilizing different egress mechanisms suggest that observed antiviral effect depend on selective inhibition of viruses budding from the cell surface. [ABSTRACT FROM AUTHOR]

The review presents recent developments in the synthesis of polymeric photosensitizers and hybrid photocatalysts of various physicochemical and photochemical properties and their possible application for the degradation of water pollutants. The mechanisms of their action were presented. Photoactive amphiphilic polymers are selective and mild reagents acting as singlet oxygen generators or via photoinduced electron transfer. They can function independently as nano/micro heterogeneous photosensitizers or as components of the hybrid systems. The hybrid materials are usually dispersed in water and are involved in the generation of very reactive oxygen species, mostly superoxide and hydroxyl radical ions, which can oxidize organic compounds present in water. These systems are generally more photostable than photoactive polymers therefore they may function as photocatalysts. Polymeric and hybrid photocatalysts are especially well-suited for removal of chemical compounds which, although present at low concentrations in water resources, are dangerous due to their bioaccumulation in the food chain and often cannot be removed with the use of currently available technologies. Both photoactive polymeric and hybrid materials can be easily removed from the aqueous media thus the secondary contamination is avoided. [ABSTRACT FROM AUTHOR]

To date, six human coronaviruses have been known, all of which are associated with respiratory infections in humans. With the exception of the highly pathogenic SARS and MERS coronaviruses, human coronaviruses (HCoV-NL63, HCoV-OC43, HCoV-229E, and HCoV-HKU1) circulate worldwide and typically cause the common cold. In most cases, infection with these viruses does not lead to severe disease, although acute infections in infants, the elderly, and immunocompromised patients may progress to severe disease requiring hospitalization. Importantly, no drugs against human coronaviruses exist, and only supportive therapy is available. Previously, we proposed the cationically modified chitosan, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), and its hydrophobically-modified derivative (HM-HTCC) as potent inhibitors of the coronavirus HCoV-NL63. Here, we show that HTCC inhibits interaction of a virus with its receptor and thus blocks the entry. Further, we demonstrate that HTCC polymers with different degrees of substitution act as effective inhibitors of all low-pathogenic human coronaviruses. [ABSTRACT FROM AUTHOR]

The article discusses the findings of a study to determine the effect of ionic strength on the lower critical solution temperature of hydroxypropylcellulose polymers. It notes the preparation of cationic polyelectrolyte from grafted N-vinylformamide, and the hydrolysis of formamide to the amine groups. This experiment confirms the formation of polymer-surfactant complexes from the strong interaction of graft copolymers with sodium dodecyl sulfate (SDS).

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Novel water-soluble polymeric photosensitizers based on a natural polymer, naphthalene-modified hydroxyethylcellulose (HENC), were obtained and used for the photooxidation of cyanide. The reaction leads to the formation of cyanate. The process occurs via photoinduced electron transfer from CN− to the naphthalene or naphthoquinone polymeric chromophores. The kinetics of the reaction depend on the degree of substitution of HENC, its concentration, and pH of the solution. The polymers can be easily removed after reaction as prolonged irradiation leads to their photodegradation. [ABSTRACT FROM AUTHOR]

Abstract: The human coronavirus NL63 is generally classified as a common cold pathogen, though the infection may also result in severe lower respiratory tract diseases, especially in children, patients with underlying disease, and elderly. It has been previously shown that HCoV-NL63 is also one of the most important causes of croup in children. In the current manuscript we developed a set of polymer-based compounds showing prominent anticoronaviral activity. Polymers have been recently considered as promising alternatives to small molecule inhibitors, due to their intrinsic antimicrobial properties and ability to serve as matrices for antimicrobial compounds. Most of the antimicrobial polymers show antibacterial properties, while those with antiviral activity are much less frequent. A cationically modified chitosan derivative, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), and hydrophobically-modified HTCC were shown to be potent inhibitors of HCoV-NL63 replication. Furthermore, both compounds showed prominent activity against murine hepatitis virus, suggesting broader anticoronaviral activity. [Copyright &y& Elsevier]

Cationic derivatives of dextran (Dex) and hydroxypropylcellulose (HPC) were studied as potential alternatives of protamine sulfate (PS) used in the reversal of anticoagulant activity of heparin. The modification was performed by the attachment of cationic groups to the Dex main chain or by grafting short side chains of a polycation onto HPC. The cationic derivatives of these polysaccharides were found to bind heparin with the efficiency increasing with growing degree of cationic modification. The degree of cationic modification and consequently the ζ potential of the polymers do not have to be high to achieve effective heparin binding. The size of the complexes of cationic Dex with unfractionated heparin (UFH) is a few micrometers. For complexes of cationic HPC and UFH the size is much below 1 μm, both below and above the lower critical solution temperature of HPC. None of the cationic polysaccharides studied caused hemolysis. The concentrations of the polymers inducing the aggregation of human erythrocytes in vitro were determined. [ABSTRACT FROM AUTHOR]

Abstract: Fluorocarbon associative polymers of the polysoap type were studied using two fluorescent probes, 1-octanoylpyrene (OcPyH) and 1-perfluorooctanoylpyrene (OcPyF). In aqueous solution the polymers formed hydrophobic domains composed of hydrocarbon, fluorocarbon or both types of polymeric side chains, which could solubilize the probes. This resulted in the appearance of new fluorescence emission bands and changes in the fluorescence polarization of the probes. The differences in the solubilization properties of the polymers are discussed. [Copyright &y& Elsevier]