Copolymers Of N-vinylpyrrolidone Research Articles

Dual hydrophobe and phenylboronic acid-grafted poly(vinylpyrrolidone) polymers as shear-thinning and mucoadhesive eyedrop formulations

Event Abstract Back to Event Dual hydrophobe and phenylboronic acid-grafted poly(vinylpyrrolidone) polymers as shear-thinning and mucoadhesive eyedrop formulations Sahar Mokhtari1, Paniz Sheikholeslami1, Jacqueline Chau1, Ben Muirhead2, Heather Sheardown1, 2 and Todd Hoare1, 2 1 McMaster University, Department of Chemical Engineering, Canada 2 McMaster University, School of Biomedical Engineering, Canada Introduction: Effective drug delivery to the eye is challenging due to the multiple biological barriers promoting rapid clearance, with as little as ~5% of drugs administered via eyedrops reaching the cornea[1]. Shear-associative hydrogels cross-linked via physical interactions that can be broken under stress offer a potential solution given that (a) they are easily to administer (b) they can self-lubricate blinking and (c) they can be engineered with different viscosities to control release kinetics[2],[3]. Adding a mucoadhesive functionality offers further potential to enhance the residence time in the tear film and thus reduce the required frequency of eyedrops. Herein, we describe a physically-gelling hydrogel formulation based on poly(vinylpyrrolidone) (PVP) chemically modified with both hydrophobes (C8 – C18) and phenylboronic acid (PBA) mucoadhesive groups[4] with potential to interact with each layer of the tear film (mucoadhesion to cornea, self-associations between hydrophobes and free mucin-PBA interactions in the aqueous, and hydrophobe assembly in the lipid layer, Fig. 1). Materials and Methods: Functional PVP was prepared via copolymerization of N-vinylpyrrolidone (VP) with N-vinylformamide (VF) followed by hydrolysis of VF residues to primary amines. Alkylchloride (C8 – C18) hydrophobes were then grafted to 15-20 mol% of the free amine groups via condensation, after which 4-formylphenylboronic acid was grafted to the remaining amine groups via reductive amination using sodium cyanoborohydride. Shear thinning and mucoadhesion were measured using rheology, while transmittance was measured using UV/vis spectrophotometry. Drug release kinetics of doxorubicin hydrochloride were measured using UV/vis spectrophotometry. In vitro cytotoxicity to human corneal epithelial cells (HCECs) was assessed using an MTT assay. Anterior segment biocompatibility was tested by administering 0.1 mL of 15 wt% polymer solution to the eyes of New Zealand White rabbits and scoring ocular responses using Draize scoring. Results and Discussion: Polymers containing up to 2.5 mol% hydrophobes and 19 mol% PBA showed transmissions (>90%), refractive indices (~1.348), and cytocompatibilities (>90% cell viability to HCECs, Fig. 2a) suitable for ophthalmic use, even at high concentrations (15 wt%). The polymers are highly shear-thinning, with 3-4 decades of viscosity between zero and infinite shear relatively independent of the PBA content (Fig. 2b). The excess storage modulus associated with polymer-mucin interactions is as high as >1 kPa, suggesting strong mucoadhesion (Fig. 2c). Formulations effectively prolonged release of doxorubicin hydrochloride over ~1 week (Fig. 2d). Draize scoring indicated no significant conjunctival edema or redness, secretion, corneal opacity, or iris involvement; indeed, the treated eyes showed less inflammation than the control eyes, suggesting potential benefits for dry eye treatment. Conclusion: Hydrophobically and PBA-modified PVP can form a highly shear-sensitive self-associative gel that remains transparent, demonstrates both shear thinning and mucoadhesive potential, facilitates controlled drug release, and is biologically well-tolerated in vitro and in vivo. We anticipate this polymer may offer particular utility in eyedrops for either prolonged drug release to the anterior segment and/or alone as a dry eye therapeutic. 20/20: NSERC Ophthalmic Materials Research Network (funding)

Radiation-chemical synthesis of N-vinylpyrrolidone copolymers with vinylacetic acid

Radiation-chemical synthesis of N-vinylpyrrolidone copolymers with vinylacetic acid

Contrast agents for magnetic resonance imaging based on dendronized N-vinylpyrrolidone polymers

In order to prepare polymeric contrast agents, various ways of modification of N-vinylpyrrolidone copolymers with vinylamine or acrolein with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid derivatives were investigated.

Mitochondrially Targeted Nanoparticles Based on α-TOS for the Selective Cancer Treatment.

The aim of this work is the preparation of an active nanovehicle for the effective administration of α-tocopheryl succinate (α-TOS). α-TOS is loaded in the core of nanoparticles (NPs) based on amphiphilic pseudo-block copolymers of N-vinyl pyrrolidone and a methacrylic derivative of α-TOS. These well-defined spherical NPs have sizes below 165 nm and high encapsulation efficiencies. In vitro activity of NPs is tested in hypopharynx squamous carcinoma (FaDu) cells and nonmalignant epithelial cells, demonstrating that the presence of additional α-TOS significantly enhances its antiproliferative activity; however, a range of selective concentrations is observed. These NPs induce apoptosis of FaDu cells by activating the mitochondria death pathway (via caspase-9). Both loaded and unloaded NPs act via complex II and produce high levels of reactive oxygen species that trigger apoptosis. Additionally, these NPs effectively suppress the vascular endothelial growth factor (VEGF) expression of human umbilical vein endothelial cells (HUVECs). These results open the possibility to use this promising nanoformulation as an α-TOS delivery system for the effective cancer treatment, effectively resolving the current limitations of free α-TOS administration.

Synthesis of N-vinyl-2-pyrrolidone–3-butenoic acid copolymers as drug carriers

New water-soluble copolymers of N-vinylpyrrolidone with 3-butenoic acid were prepared by radical copolymerization initiated with azobis(isobutyronitrile) or γ-radiation. The relative activities of the monomers in copolymerization were determined. The distribution of the units in the copolymer macrochains was calculated. The composition, molecular and hydrodynamic characteristics, and acute toxicity of the copolymers were determined. The copolymers were used as carriers for rifampicin antibiotic.

Synthesis and Molecular-Weight Characteristics of N-Oxidized Copolymers of N-Vinylpyrrolidone and 2-Methyl-5-Vinylpyridine

Aseries of N-oxides of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine copolymers with various degrees of oxidation were prepared via oxidation of the copolymers by peracetic acid. The N-oxidation kinetic rate constants were calculated using UV spectrophotometry. The temperature dependence of the limiting N-oxidation was determined. The molecular-weight characteristics of the N-oxidized copolymers were established using 13C NMR methods. An approach based on direct UV spectrophotometry was proposed for practical monitoring of the reaction completion (degree of conversion).

New hybrid nanostructures of C60 fullerene based on an amphiphilic copolymer of N-vinylpyrrolidone and (di)methacrylates

New hybrid macromolecular nanostructures of C60 fullerene based on an amphiphilic copolymer of N-vinylpyrrolidone with lauryl methacrylate and triethylene glycol dimethacrylate were prepared in isopropyl alcohol.

New hybrid macromolecular structures of C60 fullerene–amphiphilic copolymers of N-vinylpyrrolidone and triethylene glycol dimethacrylate

Amphiphilic copolymers of N-vinylpyrrolidone and triethylene glycol dimethacrylate, synthesized by radical copolymerization at equimolar and unequimolar brancher and chain transfer agent ratios, as well as their precipitated fractions with given chemical composition and physico-chemical characteristics were applied to produce the new stable nanoscaled macromolecular hybrid structures of C60 fullerene through spontaneous aggregation of copolymer particles in isopropyl alcohol and C60 molecules dissolved in toluene. FTIR and electronic absorption spectroscopy data indicate the formation of the macromolecular complex of “guest-host” as a result of the C60 solubilization by the polymer particles. The electron structure of fullerene was changed rapidly or slowly in this complex due to donor–acceptor interaction depending on copolymer kind in the solution. According to WAXS, the encapsulated fullerene molecularly dispersed in solid copolymer matrix. The dynamic characteristics (diffusion coefficients Dt and hydrodynamic radii Rh) of hybrid macromolecular structures in polar media (isopropyl alcohol, water) were determined. Cryo-TEM image shows the core–shell particles of hybrid macromolecular structure; the fullerene particles of about 3nm size were visible in the core of micellar particles.

Insight into miscibility behaviour of cellulose ester blends with N-vinyl pyrrolidone copolymers in terms of viscometric interaction parameters

We previously offered miscibility maps for blend systems of cellulose esters (CEs) including cellulose acetate (CA), propionate (CP), and butyrate (CB) with vinyl copolymers containing an N-vinyl pyrrolidone (VP) unit, i.e., poly(N-vinyl pyrrolidone-co-vinyl acetate) [P(VP-co-VAc)] and poly(N-vinyl pyrrolidone-co-methyl methacrylate) [P(VP-co-MMA)]; the maps were constructed based on data of thermal analysis as a function of the degree of ester substitution (DS) of the CE component and the VP fraction in the copolymer component. The blend system using CP among the three CEs imparted the largest region of miscible pairings with the vinyl copolymers, and both of the maps for the CP/P(VP-co-VAc) and CP/P(VP-co-MMA) systems comprised a “miscibility window” associated with the respective copolymer compositions at high DSs of >2.65. The present work was made to interpret the expansion of the miscible markings for the CP/copolymer systems in comparison with the cases using CA and CB, in terms of a Krigbaum–Wall interaction parameter (μ) obtained by solution viscometry for selective polymer pairs involved in the respective CE/copolymer blends. The results of μ measurements were in good accordance with the earlier miscibility estimations. The assessment of very small negative μ values (i.e., extremely weak repulsion) for CP/PVAc and CP/PMMA combinations and that of considerably larger negative μ values for PVP/PVAc and PVP/PMMA combinations enabled us to give a rational explanation for the CP systems. The strongly repellent character of the two different monomer units constituting the copolymers permits accession of the CP component (DS > 2.65) to them, which would be responsible for the advent of the miscibility window. Further expansion of the window observed when cellulose acetate propionate (CAP) was adopted instead of CP as the CE component was also well explained on the basis of a μ data indicative of additional intramolecular repulsion in the CAP side.

Thermoresponsive polymer coated gold nanoparticles: from MADIX/RAFT copolymerization of N-vinylpyrrolidone and N-vinylcaprolactam to salt and temperature induced nanoparticle aggregation

In the present contribution, we report the synthesis of thermoresponsive homo and statistical copolymers of N-vinylcaprolactam and N-vinylpyrrolidone and the corresponding responsive gold nanoparticles.

Створення нових поліуретансечовин з декаметоксином, що містять фрагменти кополімеру N-вінілпіролідону з вініловим спиртом

Створення нових поліуретансечовин з декаметоксином, що містять фрагменти кополімеру N-вінілпіролідону з вініловим спиртом

DEVELOPMENT OF THE METHOD FOR PREDICTING FIELD DOSAGE OF KINETIC HYDRATE INHIBITOR

The increased application of low dosage hydrate inhibitors in oil and gas production has made it necessary to develop a method for determining the consumption rates of kinetic hydrate inhibitors, as no techniques are currently available for that purpose. The method was developed in the experiments with the kinetic hydrate inhibitor SONHYD-1801A, representing a stereoregular copolymer of N-vinylpyrrolidone and caprolactam. The currently used technology for application of kinetic hydrate inhibitor SONHYD-1801A has been improved, allowing effective prevention of hydrate formation in pipelines. It is stated that the chemical can be used for continuous injection in the oil, oil-gas and oil/gas-condensate fields to prevent hydrate formation during the production and transportation of associated gas within the limited temperature and pressure range. For the experiment, a model gas hydrate-forming mixture was prepared, consisting of methane and propane in the ratio of 60/40 respectively, and with a 99.98% purity of the components. This gas mixture simulates the composition of both associated gas and gas produced from oil-gas-condensate fields. Based on the investigations performed, it is established that the kinetic hydrate inhibitor SONHYD-1801A is able to reduce the hydrate equilibrium temperature within the range of 14˚C against the equilibrium temperature. The operating pressure range is up to 15 MPa, and the inhibiting capacity is not reduced considerably as in the case with low temperatures. An empirical equation has been obtained that shows kinetic hydrate inhibitor consumption vs. pressure, temperature and water content of the gas mixture. Based on the equation, a method has been developed for optimal consumption of kinetic hydrate inhibitor under various gas flow regimes.

Self-organization and aggregation of amphiphilic block copolymers of N-vinylpyrrolidone—block-2,2,3,3-tetrafluoropropylmethacrylate at interfaces

The physicochemical characteristics of monolayer formation of amphiphilic block copolymers of N-vinylpyrrolidone—block-2,2,3,3-tetrafluoropropylmethacrylate (PVP—block-PFMA) with different molecular weights (Mw) at the water-air interface and on the solid support (quartz, silicon) were studied. It was shown by UV and IR spectroscopy, analysis of the θ—S compression isotherms, and imaging by atomic force microscopy (AFM) that the state of PVP—block-PFMA monolayers on the aqueous subphase and solid support is determined by the ratio of Mw of comonomer blocks Mw(PFMA)/Mw(PVP), the aggregation of copolymers in solution and in the surface layer (surface micellation and phase isolation). Gibb’s surface energy of the films calculated in the Wendt—Good—Kaelbly—Dan—Fowkes approximation increases up to 30–33 mJ m−2 from 21 mJ m−2 (PFMA). The values of adhesion work Wadh(monolayer—water droplet—air) and Wadh(monolayer—water in octanol) and AFM imaging characterize the lipophilicity and surface topology of the films as optimal for thromboresistant materials.

New Anticorrosion Coatings Based on Crosslinked Copolymers of Pyrrole and Epoxy-Containing Compounds

Anticorrosion coatings based on a crosslinked copolymer of pyrrole and glycidyl methacrylate and also a copolymer of N-vinylpyrrolidone and allyl glycidyl ether were obtained on the surface of iron and zinc. The inhibition of corrosion by polypyrrole was shown, a mechanism of the process was proposed, and the synthesis of coatings was optimised.

SYNTHESIS, CHARACTERISATION AND ANTIBACTERIAL ACTIVITY OF COPOLYMER (N-VINYLPYRROLIDONE – MALEIC ANHYDRIDE) WITH N- DIETHYLETHANOLAMINE

A copolymer of N-vinylpyrrolidone (NVP) with maleic anhydride (MA) is synthesized by radical copolymerization with 2,2-Azobisisobutyronitrile(AIBN) as initiator at 65 0 C in dioxane solution, under nitrogen atmosphere. The copolymer obtained is characterized by FTIR and NMR. The copolymer is made to interact with N,N-Diethylaminoethanol (DEAE) in different ratios. The susceptibility of some Gram - negative bacteria like Klebsiella aerogenes NCIM-2098, Escherichia coli NCIM-5051, Pseudomonasaeruginosa NCIM2242, Pseudomonas desmolyticum NCIM-2028 and a Gram positive bacteria Staphylococcus aureus NCIM-5022, to the copolymer and its compound with N,N-Diethylaminoethanol of different compositions in microbiological medium is studied by Agar well diffusion method. The resulting polymeric antibacterial material is useful in a number of medicines and food industry.

A new rotating-disk sorptive extraction mode, with a copolymer of divinylbenzene and N-vinylpyrrolidone trapped in the cavity of the disk, used for determination of florfenicol residues in porcine plasma

A novel extraction approach was developed based on rotating-disk sorptive extraction (RDSE). In this approach the rotating-disk extraction device consists of a Teflon disk, with a cavity that is loaded with a commercial sorbent phase selected according to the polarity of the analyte. To avoid leakage of the sorbent, the cavity is covered with a fiberglass filter and sealed with a Teflon ring. The proposed novel analytical RDSE technique was used in this study to determine florfenicol levels in plasma as a model analyte, or sample system, to describe the pharmacokinetics of a veterinary formulation. The sorbent used for this application was the copolymer of divinylbenzene and N-vinylpyrrolidone (Oasis HLB), which was selected because the florfenicol molecule contains both hydrophilic and lipophilic moieties. After the extraction, final determination of the analyte was performed by HPLC-DAD. Calibration plots and other analytical features were obtained after 90 min of extraction. The calibration plot was linear over the interval 0.4-16 μg mL(-1) (n = 6), with R (2) = 0.9999. Recovery and repeatability were determined using a blank plasma sample spiked with 4.8 μg mL(-1) florfenicol. A recovery of 91.5 %, with a relative standard deviation (RSD) of 8.8 %, was obtained when the extraction was evaluated using six different rotating-disk devices. Precision was also assessed, using the same disk (containing the same sorbent phase) for eight aliquots of the same sample. The RSD under these conditions was 10.2 %, clearly indicating that the sorptive phase could possibly be re-used. Accordingly, RDSE is a suitable sample preparation alternative to liquid-liquid extraction (LLE), solid-phase extraction (SPE), and stir-bar sorptive extraction (SBSE).

Study of operational characteristics of kinetic hydrate inhibitors during their application and disposal at oil and gas production sites

A comparative study of various types of hydrate inhibitors (thermodynamic and kinetic) was conducted along with a discussion of the advantages and disadvantages of each class of inhibitor. The increased application of low dosage hydrate inhibitors has made it necessary to evaluate possible negative consequences of the use of these chemicals in relation to injection equipment and reservoir properties during their disposal through injection wells together with produced water. The kinetic hydrate inhibitor, SONHYD-1801А, a stereoregular copolymer of N-vinylpyrrolidone and caprolactam, was chosen for laboratory testing. The kinetic hydrate inhibitor corrosiveness testing was conducted by a gravimetric method, based on the state standard test procedure GOST 9.506-87 “Corrosion Inhibitor Evaluation for Metals in Water - Petroleum Environments”. These test results gave a corrosion rate of 0.009 mm/year. For this reason, SONHYD-1801А was considered only slightly corrosive. The impact of this kinetic hydrate inhibitor on reservoir porosity and permeability was evaluated. An automated set-up was used in the tests for determination of reservoir properties of a core sample under the conditions which are close to in-situ environment. The set-up allows pumping various liquids through a core sample at a constant speed or constant pressure drop. The results showed that the tested hydrate inhibitor slightly improves reservoir properties by as much as ten percent due to the presence of surfactants in its structure. In compliance with the standards of oil companies (United Technical Requirements to Main Classes of Chemicals, No. П1-01.05 М-0044б OAO NK Rosneft), the compatibility of hydrate inhibitor with formation waters and produced gas condensate was determined. The evaluation of compatibility of hydrate inhibitor with produced waters of various salinity confirmed that the chemical is fully compatible with formation waters and gas condensate of the Zaikinskoye oilfield, without causing turbidity and precipitation.

Fullerene-containing macromolecular structures based on amphiphilic N-vinylpyrrolidone copolymers: Preparation and characterization

Fullerene-containing macromolecular structures have been obtained via aggregation of polymer colloids (micelles and intermicellar clusters), formed by amphiphilic of N-vinylpyrrolidone copolymers in isopropyl alcohol, with C60 fullerene dissolved in toluene. Their structure and behavior in solution have been investigated.

Synthesis and properties of a well-defined copolymer of chlorotrifluoroethylene and N-vinylpyrrolidone by xanthate-mediated radical copolymerization under 60Co γ-ray irradiation

RAFT/MADIX polymerization of CTFE and NVP under 60Co γ-ray irradiation with S-benzyl O-ethyl dithiocarbonate (BEDTC).

Synthesis and thermal degradation property study of N-vinylpyrrolidone and acrylamide copolymer

A series of acrylamide (AM) and N-vinylpyrrolidone (NVP) copolymer with various NVP content were synthesised by free radical solution polymerization.