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An amphiphilic copolymer of N-vinyl-2-pyrrolidone and acrylic acid-namely, p(VP-AA)-OD6000 (p(VP-AA))-was synthesized to prepare p(VP-AA) nanoparticles (NPs). Furthermore, the copolymer was linked with CFSE, and the so-prepared nanoparticles were loaded with the DiI dye to form D nanoparticles (DNPs). In this study, as demonstrated by immunofluorescence microscopy, immunofluorescence, and confocal microscopy, DNPs were readily taken up by human microvascular endothelial cells (HMEC-1) cells in a concentration-dependent manner. Upon uptake, both the CFSE dye (green stain) and the DiI dye (red stain) were localized to the cytoplasm of treated cells. Treatment with p(VP-AA) did not affect the viability of normal and challenged with LPS, HMEC-1 cells at 0.010 mg/mL and induced a dose-dependent decrease of these cells' viability at the higher concentrations of 0.033 and 0.066 mg/mL ( p ≤ 0.01; p ≤ 0.001, respectively). Furthermore, we focused on the potential immunological activation of HMEC-1 endothelial cells upon p(VP-AA) NPs treatment by assessing the expression of adhesion molecules (E-Selectin, ICAM-1, and V-CAM). NPs treatments at concentrations utilized ( p = NS) did not affect individual adhesion molecules' expression. p(VP-AA) NPs do not activate the endothelium and do not affect its viability at pharmacologically relevant concentrations.

Application of nanocarriers for drug delivery brings numerous advantages, allowing both minimization of side effects common in systemic drug delivery and improvement in targeting, which has made it the focal point of nanoscience for a number of years. While most of the studies are focused on encapsulation of hydrophobic drugs, delivery of hydrophilic compounds is typically performed via covalent attachment, which often requires chemical modification of the drug and limits the release kinetics. In this paper, we report synthesis of biphilic copolymers of various compositions capable of self-assembly in water with the formation of nanoparticles and suitable for ionic binding of the common anticancer drug doxorubicin. The copolymers are synthesized by radical copolymerization of N-vinyl-2-pyrrolidone and acrylic acid using n-octadecyl-mercaptan as a chain transfer agent. With an increase of the carboxyl group's share in the chain, the role of the electrostatic stabilization factor of the nanoparticles increased as well as the ability of doxorubicin as an ion binder. A mathematical description of the kinetics of doxorubicin binding and release is given and thermodynamic functions for the equilibrium ionic binding of doxorubicin are calculated.

Microbubbles are routinely used ultrasound contrast agents in the clinic. While a soft protein shell is commercially preferable for imaging purposes, a rigid polymer shell demonstrates prolonged agent stability. Hence, combining polymers and proteins in one shell composition can advance microbubble properties. We formulated the hybrid "protein-copolymer" microbubble shell with a complex of bovine serum albumin and an amphiphilic copolymer of N -vinyl-2-pyrrolidone and acrylic acid. The resulting microbubbles demonstrated advanced physicochemical and acoustic properties, preserving in vitro biocompatibility. Adjusting the mass ratio between protein and copolymer allowed fine tuning of the microbubble properties of concentration (by two orders, up to 10 10 MBs/mL), mean size (from 0.8 to 5 μm), and shell thickness (from 28 to 50 nm). In addition, the minimum air-liquid surface tension for the "protein-copolymer" solution enabled the highest bubble concentration. At the same time, a higher copolymer amount in the bubble shell increased the bubble size and tuned duration and intensity of the contrast during an ultrasound procedure. Demonstrated results exemplify the potential of the hybrid "protein-polymer" microbubble shell, allowing tailoring of microbubble properties for image-guided applications, combining advances of each material involved in the formulation.

Development of nanocarrier-based drug delivery systems is a major breakthrough in pharmacology, promising targeted delivery and reduction in drug toxicity. On the cellular level, encapsulation of a drug substantially affects the endocytic processes due to nanocarrier-membrane interaction. In this study we synthesized and characterized nanocarriers assembled from amphiphilic oligomers of N -vinyl-2-pyrrolidone with a terminal thiooctadecyl group (PVP-OD). It was found that the dissolution free energy of PVP-OD depends linearly on the molecular mass of its hydrophilic part up to M¯n = 2 × 10 4 , leading to an exponential dependence of critical aggregation concentration (CAC) on the molar mass. A model hydrophobic compound (DiI dye) was loaded into the nanocarriers and exhibited slow release into the aqueous phase on a scale of 18 h. Cellular uptake of the loaded nanocarriers and that of free DiI were compared in vitro using glioblastoma (U87) and fibroblast (CRL2429) cells. While the uptake of both DiI/PVP-OD nanocarriers and free DiI was inhibited by dynasore, indicating a dynamin-dependent endocytic pathway as a major mechanism, a decrease in the uptake rate of free DiI was observed in the presence of wortmannin. This suggests that while macropinocytosis plays a role in the uptake of low-molecular components, this pathway might be circumvented by incorporation of DiI into nanocarriers.

It was found that sulfanylethanoic and 3-sulfanylpropanoic acids are effective regulators of molecular weight with chain transfer constants of 0.441 and 0.317, respectively, and show an unexpected acceleration effect on the radical polymerization of N-vinyl-2-pyrrolidone, initiated by 2,2'-azobisisobutyronitrile. It was determined for the first time that the thiolate anions of mercapto acids form a high-temperature redox initiating system with 2,2'-azobisisobutyronitrile during the radical polymerization of N-vinyl-2-pyrrolidone in 1,4-dioxane. Considering the peculiarities of initiation, a kinetic model of the polymerization of N-vinyl-2-pyrrolidone is proposed, and it is shown that the theoretical orders of the reaction rate, with respect to the monomer, initiator, and chain transfer agent, are 1, 0.75, 0.25, and are close to their experimentally determined values. Carboxyl-containing techelics of N-vinyl-2-pyrrolidone were synthesized so that it can slow down the release of the anticancer drug, doxorubicin, from aqueous solutions, which can find its application in the pharmacological field.

The kinetic regularities of the initial stage of chemical oxidative polymerization of methylene blue under the action of ammonium peroxodisulfate in an aqueous medium have been established by the method of potentiometry. It was shown that the methylene blue polymerization mechanism includes the stages of chain initiation and growth. It was found that the rate of the initial stage of the reaction obeys the kinetic equation of the first order with the activation energy 49 kJ × mol -1 . Based on the proposed mechanism of oxidative polymerization of methylene blue and the data of MALDI, EPR, and IR spectroscopy methods, the structure of the polymethylene blue chain is proposed. It has been shown that polymethylene blue has a metallic luster, and its electrical conductivity is probably the result of conjugation over extended chain sections and the formation of charge transfer complexes. It was found that polymethylene blue is resistant to heating up to a temperature of 440 K and then enters into exothermic transformations without significant weight loss. When the temperature rises above 480 K, polymethylene blue is subject to endothermic degradation and retains 75% of its mass up to 1000 K., Competing Interests: The authors declare no conflict of interest.

Background: The pandemic associated with the new SARS-CoV-2 coronavirus continues to spread worldwide. The most favorable epidemic control scenario, which provides long-term protection against COVID-19 outbreak, is the development and distribution of an effective and safe vaccine. The need to develop a new COVID-19 vaccine is pressing; however, it is likely to take a long time, possibly several years. This is due to the time required to demonstrate the safety and efficacy of the proposed vaccine. and the time required to manufacture and distribute millions of doses., Objectives: To accelerate this development and associated safety testing, the deliberate infection of healthy volunteers has been suggested. The purpose of this short communication is to describe the ethical aspects of this type of testing, RESULTS: Deliberate infection of volunteers with a dangerous virus such as SARS-CoV-2 was initially considered unethical by researchers; but the current pandemic is so different from previous ones that these studies are considered ethical if certain criteria are met. Participants in human challenge studies must be relatively young, in good health and must receive the highest quality medical care, with frequent monitoring. Tests should also be performed with great caution and specialized medical supervision. Besides, the fact that obtaining vaccines faster through deliberate infection studies of healthy people has greater benefits than risks, has been demonstrated by obtaining other vaccines in other historical pandemics such as: smallpox, influenza, malaria, typhoid fever, Dengue fever and Zika., Conclusions: One possibility to shorten the time required for the development of COVID-19 vaccines is to reduce clinical phases II and III by using human challenge studies through eliberate infection of healthy volunteers with SARS-CoV-2 after administration of the candidate vaccine. Accelerating the development of a COVID-19 vaccine even for a few weeks or months would have a great beneficial impact on public health by saving many lives.

In the current context of the pandemic triggered by SARS-COV-2, the immunization of the population through vaccination is recognized as a public health priority. In the case of SARS‑COV‑2, the genetic sequencing was done quickly, in one month. Since then, worldwide research has focused on obtaining a vaccine. This has a major economic impact because new technological platforms and advanced genetic engineering procedures are required to obtain a COVID‑19 vaccine. The most difficult scientific challenge for this future vaccine obtained in the laboratory is the proof of clinical safety and efficacy. The biggest challenge of manufacturing is the construction and validation of production platforms capable of making the vaccine on a large scale.

Venous thromboembolism is a frequent complication occurring in patients suffering from neoplastic diseases. Since neutrophil extracellular traps (NETs) play an important role both in the development of the tumor growth process and in inducing complications such as thrombosis, indubitably the investigation of the effect of antitumor drugs on the formation of neutrophil extracellular traps and on the ability of such drugs to prevent NETs contribution on carcinogenesis is of great interest. In the present work we studied the effect of 5-fluorouracil (5FU) and its shielded -by amphiphilic poly-N-vinylpyrrolidone (Amph-PVP) nanoparticles-nanoscaled polymeric form on the activation of human neutrophils under ex vivo conditions. Free 5FU at concentrations varying from 0.01 to 10 mg/ml was found to cause a significant (two to three times) and rapid (after 20 min) increase in the total amount of NETs in the blood. Importantly, when 5FU-loaded Amph-PVP nanoparticles were studied under the same conditions, the appearance of NETs in the blood was completely blocked providing strong evidence of their potential as delivery system for 5FU in antitumor therapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study focused on defining the in vitro behavior of amphiphilic poly-N-vinylpyrrolidone (Amph-PVP) nanoparticles toward whole blood, blood plasma and blood cells in order to assess nanoparticle blood compatibility. In addition, possible effects on endothelium cell growth/viability were evaluated. The Amph-PVP nanoparticles were formed via self-assembling in aqueous media and composed of a hydrophobic alkyl core and a hydrophilic PVP outer shell. Their blood compatibility was evaluated by investigating their effect on red blood cells (RBCs) or erythrocytes, white blood cells (WBCs) or leukocytes, platelets (PLTs) and on complement system activation. Our results clearly demonstrate that the Amph-PVP nanoparticles are stable in presence of blood serum, have no significant effects on the function of RBCs, WBCs, PLTs and complement system activation. The Amph-PVP nanoparticles did not show considerable hemolytic or inflammatory effect, neither influence on platelet aggregation, coagulation process, or complement activation at the tested concentration range of 0.05-0.5 mg/ml. The Amph-PVP nanoparticles did not exhibit any significant effect on HMEC-1 microvascular skin endothelial cells' growth in in vitro experiments. The excellent blood compatibility of the Amph-PVP nanoparticles and the lack of effect on endothelium cell growth/viability represent a crucial feature dictating their further study as novel drug delivery systems., (Copyright © 2019. Published by Elsevier Ltd.)

Gold nanoparticles are currently investigated as theranostics tools in cancer therapy due to their proper biocompatibility and increased efficacy related to the ease to customize the surface properties and to conjugate other molecules. Betulin, [lup-20(29)-ene-3β, 28-diol], is a pentacyclic triterpene that has raised scientific interest due to its antiproliferative effect on several cancer types. Herein we described the synthesis of surface modified betulin-conjugated gold nanoparticles using a slightly modified Turkevich method. Transmission electron microscopy (TEM) imaging, dynamic light scattering (DLS), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) were used for the characterization of obtained gold nanoparticles. Cytotoxic activity and apoptosis assessment were carried out using the MTT and Annexin V/PI apoptosis assays. The in vitro results showed that betulin coated gold nanoparticles presented a dose-dependent cytotoxic effect and induced apoptosis in all tested cell lines.

Aim: Ability to deliver drugs into the cell nuclei can significantly increase the efficacy of cancer therapies, in particular in the case of multidrug-resistant cancer Results: Polymer nanocarriers based on amphiphilic thiooctadecyl-terminated poly-N-vinyl-2-pyrrolidone were produced and loaded with a model hydrophobic drug, curcumin. Two commonly used loading approaches - emulsification and ultrasonic dispersion - were found to lead to two different size distributions with distinctively different biological effect. While nanocarriers produced via the emulsion method penetrated cells by dynamin-dependent endocytic mechanisms, sub-100 nm dispersion-produced nanocarriers were capable of crossing the membranes via biologically independent mechanisms., Conclusion: This finding opens an intriguing possibility of intranuclear delivery by merely tailoring the size of polymeric carriers, thus promising a new approach for cancer therapies.

Extracellular matrix (ECM) is an extraordinarily complex and unique meshwork composed of structural proteins and glycosaminoglycans. The ECM provides essential physical scaffolding for the cellular constituents, as well as contributes to crucial biochemical signaling. Importantly, ECM is an indispensable part of all biological barriers and substantially modulates the interchange of the nanotechnology products through these barriers. The interactions of the ECM with nanoparticles (NPs) depend on the morphological characteristics of intercellular matrix and on the physical characteristics of the NPs and may be either deleterious or beneficial. Importantly, an altered expression of ECM molecules ultimately affects all biological processes including inflammation. This review critically discusses the specific behavior of NPs that are within the ECM domain, and passing through the biological barriers. Furthermore, regenerative and toxicological aspects of nanomaterials are debated in terms of the immune cells-NPs interactions.

Poly(vinyl alcohol) (PVA) hydrogels are widely employed for various biomedical applications, including tissue engineering, due to their biocompatibility, high water solubility, low protein adsorption, and chemical stability. However, non-charged surface of PVA-based hydrogels is not optimal for cell adhesion and spreading. Here, cross-linked macroporous hydrogels based on low molecular weight acrylated PVA (Acr-PVA) was synthesized by modification of the pendant alcohol groups on the PVA with glycidyl methacrylate (GMA). To enhance cell affinity, charged groups were introduced to the hydrogel composition. For this purpose, Acr-PVA was copolymerized with either negatively charged acrylic acid (AA) or positively charged 2-(diethylamino) ethyl methacrylate (DEAEMA) monomers. A surface charge of the obtained hydrogels was found to be in function of the co-monomer type and content. Confocal microscopy observations confirmed that adhesion and spreading of both mouse fibroblasts (L929) and human mesenchymal stem cells (hMSC) on the modified Acr-PVA-AA and Acr-PVA-DEAEMA hydrogels were better than those on the non-modified Acr-PVA hydrogel. The increase of DEAEMA monomer content from 5 to 15mol% resulted in the enhancement of cell viability which was 1.5-fold higher for Acr-PVA-DEAEMA-15 hydrogel than that of the non-modified Acr-PVA hydrogel sample., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Polymeric nanoparticles were prepared from self-assembled amphiphilic N-vinylpyrrolidone polymers in aqueous media and evaluated as novel carriers of indomethacin, a non-steroidal, anti-inflammatory drug. It was determined that these nanoparticles could be created in spherical morphologies with sizes less than 100nm, narrow size distributions and high indomethacin contents(up to 35%) combined with high drug loading efficiencies(up to 95%). In cytotoxicity tests using the human embryonic stem cell derived fibroblasts (EBF-H9) and hepatocellular carcinoma cells (HepG2), the indomethacin-loaded polymeric nanoparticles showed higher cell viability compared to that of free indomethacin at the same concentration. The median LD 50 values, determined by the Litchfield-Wilcoxon method, were 55-70mg/kg body weight depending on the polymer molecular design in both mice and rats. Based on the acquired results, these novel amphiphilic poly-N-vinylpyrrolidone nanoparticles can be considered as potential carriers for new, highly efficient, injectable drug delivery systems for hydrophobic drugs such as indomethacin., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The aim of the present study was to evaluate the cytotoxicity against MCF-7 cells and acute intraperitoneal toxicity of amphiphilic poly-N-vinylpyrrolidone nanoparticles to confirm possibility of their application for creation of novel drug delivery systems. The effect of cellular uptake of polymeric nanoparticles on human cancer cell line MCF-7 cells was investigated by MTT assay. MTT analysis showed that tested amphiphilic polymers were essentially non-toxic. In acute toxicity studies, LD50 and other toxicity indexes were evaluated, under which no deaths or treatment related complications were observed even in high concentration treatment for 14 days of experiment. For histological analysis, organs of the animals were weighed and examined. No animal died during the study and no significant changes have been observed regarding body weight, feed consumption, organ weight or histological data. Obtained results show that amphiphilic poly-N-vinylpyrrolidone nanoparticles possessed no toxicity against cells and in animals after intraperitoneal administration. Thus, amphiphilic PVP nanoparticles demonstrate high potential as carriers for novel high-effective drug delivery systems., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Nanotechnology is an evolving scientific field that has allowed the manufacturing of materials with novel physicochemical and biological properties, offering a wide spectrum of potential applications. Properties of nanoparticles that contribute to their usefulness include their markedly increased surface area in relation to mass, surface reactivity and insolubility, ability to agglomerate or change size in different media and enhanced endurance over conventional-scale substance. Here, we review nanoparticle classification and their emerging applications in several fields; from active food packaging to drug delivery and cancer research. Nanotechnology has exciting therapeutic applications, including novel drug delivery for the treatment of cancer. Additionally, we discuss that exposure to nanostructures incorporated to polymer composites, may result in potential human health risks. Therefore, the knowledge of processes, including absorption, distribution, metabolism and excretion, as well as careful toxicological assessment is critical in order to determine the effects of nanomaterials in humans and other biological systems. Expanding the knowledge of nanoparticle toxicity will facilitate designing of safer nanocomposites and their application in a beneficial manner., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Various biomolecules, for example proteins, peptides etc., entrapped in polymer matrices, impact interactions between matrix and cells, including stimulation of cell adhesion and proliferation. Delta-sleep inducing peptide (DSIP) possesses numerous beneficial properties, including its abilities in burn treatment and neuronal protection. DSIP entrapment in two macroporous polymer matrices based on copolymer of dimethylaminoethyl methacrylate and methylen-bis-acrylamide (Co-DMAEMA-MBAA) and copolymer of acrylic acid and methylen-bis-acrylamide (Co-AA-MBAA) has been studied. Quite 100% of DSIP has been entrapped into positively charged Co-DMAEMA-MBAA matrix, while the quantity of DSIP adsorbed on negatively charged Co-AA-MBAA was only 2-6%. DSIP release from Co-DMAEMA-MBAA was observed in saline solutions (0.9% NaCl and PBS) while there was no DSIP release in water or 25% ethanol, thus ionic strength was a reason of this process., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Previous studies have demonstrated functional roles for microRNAs (miRNAs) in various aspects of normal and malignant hematopoiesis, including lineage commitment, differentiation, apoptosis and maturation. In vivo delivery of naked DNA, oligonucleotides and miRNAs is complicated by their low stability, rapid degradation and inefficient delivery into target cells. In our experiments, we used a new type of polymer carriers to monitor the effects of miR-155 and antago-miR-155 on the morphology and genetics of Kasumi-1 cells. We obtained platelet-like cells from leukemic cells, and detected the expression of platelet marker genes after transfection with antago-miR-155. Our findings suggest that administration of miR mimics or antago-miRs as therapeutic agents is a desirable goal for future treatment of hematologic malignancies and that polymer-based carriers for the delivery of miR mimics or antago-miRs may provide a solution to the challenges of standard miR delivery approaches.

Novel amphiphilic poly-N-vinylpyrrolidone derivatives with different molecular weight of hydrophilic PVP fragment and one secondary di-n-alkyl terminal hydrophobic fragment of different length were synthesized to compare their inclination for formation of nano-scaled micelle-like aggregates in aqueous media with previously studied primary n-alkyl terminated poly-N-vinylpyrrolidones. The behavior of amphiphilies in water solutions was studied and critical aggregation concentration values for prepared polymer samples were determined by fluorescence spectroscopy and compared with those for primary n-alkyl derivatives. Polymeric micelle-like particles with or without encapsulated drug were prepared using dialysis or solvent evaporation techniques. Indomethacin was incorporated into hydrophobic inner core of these nanoparticles as a typical model drug. Dynamic light-scattering studies determined that the average size of particles formed was from 90 nm up to 600 nm with monodisperse size distribution and the nanoparticle size slightly increased with the amount of indomethacin encapsulated into inner core of the particles. In vitro release experiments carried out at different medium pH values using indomethacin-loaded nanoparticles exhibited slow and steady drug release into the medium.

Amphiphilic poly-N-vinylpyrrolidone derivatives (Amph-PVP) with different molecular weight of hydrophilic PVP fragment and one terminal hydrophobic n-alkyl fragment of different length were synthesized for preparation of nano-scaled particles in aqueous media. To estimate novel polymer efficiency and perspective as basis for drug delivery systems, the polymeric micelle-like particles were prepared by dialysis and solvent evaporation methods. Indomethacin was incorporated into hydrophobic inner core of these nanoparticles as a typical model drug. From the dynamic light-scattering measurements, the size of particles formed was less than 200 nm with narrow monodisperse size distribution and nanoparticles size slightly increased with the amount of indomethacin encapsulated into inner core of Amph-PVP particles. The critical aggregation concentration values for prepared polymer samples determined by fluorescence spectroscopy were in micromole range which is lower than it is for common low molecular weight surfactants. As the hydrophobic fragment of amphiphilic polymer increased, the critical aggregation concentration values decreased. An increase of polymer hydrophilic fragment molecular weight produced larger nanoaggregates. In vitro release experiments using indomethacin-loaded Amph-PVP nanoparticles exhibited the sustained release behavior without any burst effect for most polymer samples.

Stearoyl-poly-N-vinylpyrrolidone (PVP-stear) of various molecular weights (M(n) = 1500-5500) self-assemble in aqueous medium. Particles prepared from PVP-stear were characterized in terms of shape and size distribution, and the mechanical stability of the particles was studied. The interaction of PVP-stear and its aggregates with blood components was investigated. Aggregates formed by the polymers with M(n) = 1500-3500 in the presence of human serum are stable. The direct lytic action of PVP-stear preparations was studied using sheep and human erythrocytes. The influence of PVP-stear aggregates on the activation of complement system both on classical and alternative pathways was examined. The aggregates prepared from PVP-stear of various molecular weights had no effect on the activation of the complement system.

Polymeric particles formed by stearoyl-poly-N-vinylpyrrolidone (PVP-stear) of M(n) = 2600 were obtained in aqueous solution, and their shape and size distribution were characterized. The size of the particles was shown to decrease with an increase in the ionic strength of the solution. Interaction of PVP-stear and its aggregates with model proteins (Bowman-Birk soybean proteinase inhibitor (BBI) and its hydrophobized derivatives) was studied. The possibility of inclusion of both native BBI and oleoylic derivative of BBI in the PVP-stear polymeric aggregates was investigated. It was established that polymeric particles with a diameter of 30 nm formed under certain concentration ratios between PVP-stear and poorly soluble dioleoyl BBI are capable of solubilization of dioleoyl BBI as well as prevention of its inactivation at low pH values.

Two poly (vinyl pyrrolidone) (PVP) families with amino-acid residues (glycine, beta-alanine, gamma-aminobutiric acid and epsilon-aminocaproic acid) on the base of the co-polymer N-vinyl pyrrolidone and allyl-glycidyl ether (VP-AGE) and on the base of epoxidized PVP (EPVP) were synthesized. Static and dynamic light scattering measurements of these PVP derivatives in water showed that their structure/ behavior were similar to that of PVP. The bioreactivity was also similar to that of PVP. Further investigation of the immunoreactive properties of the derivatives in in vitro proliferation assays with fresh normal human peripheral blood lymphocytes and monocytes led to the determination of a costimulatory profile for each derivative in terms of polyclonal stimulation, specific antigen presentation, and immunoglobulin secretion. This profile allows the selection of an appropriate derivative as a carrier that would suit the immunoreactivity needs of the immobilized ligand., (Copyright 2002 Wiley Periodicals, Inc.)

Certain amphiphilic water-soluble polymers including amphiphilic derivatives of polyvinyl pyrrolidone (PVP) were found to be efficient steric protectors for liposomes in vivo. In this study, we have tried to develop synthetic pathways for preparing amphiphilic PVP and to investigate the influence of the hydrophilic/hydrophobic blocks on some properties of resulting polymers and polymer-coated liposomes. To prepare amphiphilic PVP with the end stearyl (S) or palmityl (P) residues, amino- and carboxy-terminated PVP derivatives were first synthesized by the free-radical polymerization of vinyl pyrrolidone in the presence of amino- or carboxy-mercaptans as chain transfer agents, and then modified by interaction of amino-PVP with stearoyl chloride or palmitoyl chloride, or by dicyclohexyl carbodiimide coupling of stearylamine with carboxy-PVP. ESR-spectra of the hydrophobic spin-probe, nitroxyl radical N-oxyl-2-hexyl-2-(10-methoxycarbonyl)decyl-4,4'-dimethyl oxazoline, in the presence of amphiphilic PVP demonstrated good accessibility of terminal P- and S-groups for the interaction with other hydrophobic ligands. Spontaneous micellization and low CMC values (in a low micromolar range) were found for amphiphilic PVP derivatives using the pyrene method. In general, S-PVP forms more stable micelles than P-PVP (at similar MW, CMC values for S-PVP are lower than for P-PVP). It was found that amphiphilic PVP incorporated into negatively charged liposomes effectively prevents polycation(poly-ethylpyridinium-4-vinylchloride)-induced liposome aggregation, completely abolishing it at ca. 10 mol% polymer content in liposomes. Additionally, the liposome-incorporated PVP prevents the fluorescence quenching of the membrane-incorporated hydrophobic fluorescent label [N-(4-fluoresceinthiocarbamoyl)dipalmitoyl-PE] by the free polycation. PVP-modified liposomes were loaded with a self-quenching concentration of carboxyfluorescein, and their destabilization in the presence of mouse serum was investigated following the release of free dye. Amphiphilic PVP with MW between 1,500 and 8,000 provides good steric protection for liposomes. The degree of this protection depends on both polymer concentration and molecular size of the PVP block.

New controlled release water-soluble formulations of sorbic (2,4-hexadienoic) acid were prepared and their inhibitory activity on mycelium growth of Fusarium oxysporum f.sp. radicis-cucumerinum was evaluated. The new products are epoxidized polymers of polyvinylpyrrolidone (PVP) containing covalently bonded sorbic acid (polymeric esters of sorbic acid) and complexes of PVP with hydrogen bonded sorbic acid, characterized by controlled release of sorbic acid. It was shown that the polymeric complexes of sorbic acid with PVP were more effective fungicidal agents than sorbic acid polymeric esters. In all cases the activity of polymeric derivatives (esters and complexes) was increased by lowering the molecular weight of the polymeric carriers. Controlled release formulations of these polymeric derivatives are new promising products due to their low toxicity, wide range of efficient concentrations for application and ability to regulate lyophilicity. Our data contribute to the understanding of the action mechanism of various polymeric sorbic acid formulations and can result in products which are particularly suitable for food and feed protection applications.

This study describes the elimination of zearalenone concentrations in vitro using two new polymeric forms of cross-linked polyvinylpyrrolidone (cryogels of cross-linked PVP). Adsorption of zearalenone was studied under isothermal conditions and simulating pH of intestinal environment. A Freundlich isotherm was used to describe the adsorption data obtained. The results showed significant decrease of zearalenone concentrations, ranging from 33.5-66.2% per 25 mg of polymer. Adsorption capacity (k) was estimated to be higher than that of previously tested adsorbents, including crospovidone. The data indicate the need to investigate structure peculiarities in order to improve mycotoxin deactivation procedures using PVP derivatives.

Newly synthesized amphiphilic polyacrylamide and poly(vinyl pyrrolidone), single terminus-modified with long-chain fatty acyl groups, are able to incorporate into the liposomal membrane, and similar to poly(ethylene glycol) prolong liposome circulation in vivo and decrease liposome accumulation in the liver. Protective efficacy of modified polymers increases with the increase in the length of acyl moiety and decreases for higher molecular weight polymers. The data on amphiphilic polymer-modified liposome biodistribution are presented.