The formation of conjugates with PEG–chitosan improves the biocatalytic efficiency and antitumor activity of L-asparaginase from <Emphasis Type="Italic">Erwinia carotovora</Emphasis>

The ChitoPEGylation method, which is a novel approach to regulating the catalytic properties of enzymes that is based on the formation of a covalent conjugate of an enzyme with branched copolymers of chitosan, has been developed. The efficiency of this method has been demonstrated using a new recombinant preparation of L-asparaginase from Erwinia carotovora (EwA) as a model. The molecular architecture and composition of EwA conjugates with PEG–chitosans have been optimized. It has been shown that the decisive factors that affect the activity of the EwA conjugates are the molecular weight of and PEGylation degree of chitosan. It has been found that the EwA conjugation with PEG–chitosan increases, its cytostatic activity against human chronic myeloid leukemia K562 cells, Burkitt’s lymphoma Raji cells, and acute lymphoblastic leukemia Jurkat cells. These data provide new approaches to the synthesis of L-asparaginase preparations with improved biocatalytic properties.     

Synthesis, structure, and properties of branched polymethacrylates

The methacrylate: branching agent: chain growth regulator optimal ratios that allow the synthesis of branched polymethacrylates via the crosslinking free-radical copolymerization under the regime of conventional or catalytic chain transfer have been estimated. Relationships between the molecular-mass characteristics of the copolymers, their content of intact C=C bonds, the composition of the starting monomer mixture, and the structure of the branching agent and polymer chain growth regulator have been established. The rheological properties of the branched MMA-based copolymers have been studied. It has been shown that the copolymers are characterized by a weaker dependence of reduced viscosity on the polymer concentration in solution than that for the linear PMMA. The diffusion-sorption behavior of the branched polymethacrylates is determined by the content of the branching agent in them.     

Graft polymerization of acrylamide on chitosan: Copolymer structure and properties

Graft copolymers have been prepared through the free-radical polymerization of acrylamide in water-acetic acid solutions of chitosan in the presence of ammonium persulfate as an initiator. The effect of temperature, pH of a medium, and concentrations of initiator, chitosan, and acrylamide on the grafting kinetics and efficiency has been established. The local concentration of acrylamide in the reaction zone increases due to intermolecular hydrogen bonding between polysaccharide and monomer molecules. Copolymer films are characterized by better mechanical properties compared to those of polysaccharide. Hydrogels with good viscoelastic properties have been obtained when grafting was performed in the presence of N,N-methylenebisacrylamide as a crosslinking agent.     

嵌段共聚物OSM1-PCLA-PEG-PCLA-OSM1的合成及其pH和温度敏感性

采用开环聚合法和自由基聚合法合成了生物可降解嵌段共聚物OSM1-PCLA-PEG-PCLA-OSM1, 并对其进行了结构表征. 采用荧光分光光度计和激光粒度仪对共聚物溶液临界胶束浓度(CMC)和粒径大小及分布进行了考察, 研究了温度和pH对共聚物胶束形成的影响. 相转变过程研究结果表明, 共聚物溶液具有pH和温度双重敏感性. 共聚物溶液在一定温度和pH条件下可发生溶液-凝胶相转变.     

Physicochemical properties of aqueous solutions of L-aspartic acid containing chitosan

Physicochemical properties of aqueous solutions of L-aspartic acid with and without addition of chitosan have been studied by conductometry, potentiometry, refractometry, tensiometry, and viscosimetry. It has been shown that aspartic acid molecules take a cyclic configuration stabilized by hydrogen bonds in aqueous solution at c > 0.04 g/dL (298 K). The interaction of chitosan with aspartic acid results in the formation of the polymeric salt that dissociates in aqueous solution to give chitosan polycation [~(NH₃)⁺] and aspartate counterions. The addition of chitosan to solutions of L-aspartic acid results in progressive increase in the surface tension, absorbance, and refractive index as well as the change in hydrodynamic properties of the macromolecules. The polymeric salt exhibits polyelectrolyte properties in dilute aqueous solutions. The increase in temperature impairs the thermodynamic quality of the solvent for chitosan leading to the shrinkage of the polymer coils and, hence, to the decrease in the intrinsic viscosity of the system.     

Modification of chitosan via grafting of glycolic acid followed by polycondensation during heat treatment

The modification of chitosan via grafting of glycolic acid and subsequent polycondensation during heat treatment have been studied. The formation of copolymers, the degree of amidization of amino groups, and the length of side polyglycolide chains are investigated by IR spectroscopy and gravimetry. The structural features and surface behavior of the films based on chitosan modified by poly(glycolic acid) are examined by X-ray diffraction and AFM. The grafting of side polyglycolide chains leads to marked changes in the chitosan structure. The study of the sorption behavior of the films based on the modified chitosan confirms the hydrophobization of chitosan via grafting of poly(glycolic acid).     

Atypical polysaccharide physical gels: structure/property relationships

Chitin and chitosan are polysaccharides produced by the biomass. They have the same general chemical structure and constitute the series of linear copolymers of linked β, (1->4) glucosamine and N-actylglucosamine. We studied the possibility of forming physical gels with all the terms of this series, whatever the proportion of the two kinds of residues included in the polymer chains. We show that physical gelation is still possible through a percolating process when certain important conditions are met. Initially the concentration in polymer must be above C*; a critical value of the balance between hydrophobic and hydrophilic interactions must be achieved and gelation must occur simultaneously everywhere in the medium. These conditions were observed in several situations allowing the formation of different kinds of gels at all values of DA. In view of the rare bio-active properties of chitin and chitosan, these gels were tested for living tissue regeneration and constitute very interesting examples in illustration of our concept of decoys for biological media.     

Graft copolymers of poly(ethylene glycol) (PEG) and chitosan

Graft copolymers of poly(ethylene glycol) (PEG) on a chitosan backbone (PEG-g-chitosan) have been synthesized and their aqueous solution properties were investigated. At pH 6.5 the graft copolymers are 100% soluble, while chitosan phase separates from solution at those conditions. These interesting graft copolymers may be especially suitable as carriers for delivery of anionic drugs, such as proteins, glycosaminoglycans, and DNA plasmids or oligonucleotides.     

Flocculation Power of Chitosan and Its Derivatives in Mixtures with Anionic Flocculants

The flocculation properties of chitosan (cationic component) and its copolymers with (meth)acrylic acid were studied. The flocculation power of grafted chitosan copolymers with dimethylaminoethyl methacrylate in mixtures with an anionic polyacrylic flocculant was evaluated.     

Structural analysis of linear/branched ethylene block copolymers

Chain shuttling polymerization has provided new pathway for introduction of different architectures in a single chain. Unlike the commercially available ethylene/1‐octene block copolymers, synthesis and microstructure of linear/branched polyethylene with blocky nature is not extensively studied. In this work, such block copolymers are synthesized based on reversible transfer of growing chains between an ansa metallocene and α‐diimine catalysts, forming linear and branched structures from ethylene, respectively. Investigation of thermal properties reveals that application of 550 equivalent of chain shuttling agent makes blocky structures that show the most deviation from the longstanding relationship between melting temperature and crystallinity or density, alongside with turning broad molecular distribution into unimodal. Thermal fractionation by successive self‐annealing demonstrates formation of broad distribution of linear blocks, as comprehended through appearance of uniform melting peaks at lower temperatures. Corresponding dynamic mechanical properties and crystalline structures reveal soft elastomeric properties, specifically at temperatures around −50°C, opposed to the purely linear chains or linear/branched blends. Correspondingly, blend samples demonstrate significant morphological change upon treatment with a suitable solvent for the branched fraction, contrary to the blocky microstructures.     

Induced degradation of chitosan,conjugated with block copolymerization with acrylamide

Synthesis of block copolymers of chitosan with acrylamide, involving formation of acrylamide blocks on glucosamine blocks generated by induced degradation of chitosan macromolecules by the hydrogen peroxide-ascorbic acid system, was studied.     

Biodegradable systems: Thermodynamics, rheological properties, and biocorrosion

Systems based on starch and chitosan blends with synthetic polymers and cellulose derivatives (poly(ethylene oxide) and methyl cellulose of various molecular masses, PA, and ethylene-vinyl acetate copolymers containing different amounts of vinyl acetate groups) have been studied. The thermodynamic characteristics of the formation of blends have been determined. The rheological properties characterizing formation of blends from melts have been investigated. The biocorrosion ability of the blends after their use has been estimated by various methods. The concentration dependences of the thermodynamic functions of mixing of components (change in the Gibbs energy, enthalpy, and entropy) change sign in a wide composition range, indicating the complexity of mixing of rigid-chain natural polysaccharides with synthetic polymers. The rheological study of blends in which starch or chitosan plays the role of a biodegradation modifier shows that they are non-Newtonian fluids. The absolute values of viscosity and the activation parameters of melts increase with the content of polysaccharide in the system. The values of viscosity correspond to those typical for commercially processable polymers. The blends under study are biodegradable in a wet and water-soil medium with the content of the natural component being in the range 15–30 wt %.     

Rheological and relaxation properties of MQ copolymers

The rheological properties of MQ copolymer melts are investigated under steady-state shear flow and dynamic oscillatory shear within a wide temperature range. The MQ copolymers are highly branched polycyclic compounds (densely crosslinked nanosized networks) incapable of further intermolecular interactions. The samples have identical chemical compositions, but their detailed molecular structures are different. The polymers under consideration show Newtonian behavior in a wide shear-stress range. The values of viscosity vary considerably with the molecular structure of the copolymers. The generalized frequency dependence of complex dynamic modulus components is constructed with the use of the temperature-frequency superposition method. In a first approximation, the viscoelastic behavior of the materials is satisfactorily described by the Maxwell model with a single relaxation time. In this respect, the studied materials are similar to micellar colloids. The relaxation spectra of the copolymers distinguished by narrow distributions are calculated.     

Gelation time and degradation rate of chitosan-based injectable hydrogel

Gelation time and degradation rate of thermally-sensitive aqueous solutions of chitosan/Gp (glycerophosphate disodium salt) have been studied. The effects of different parameters such as Gp salt concentration, solution temperature, degree of deacetylation of chitosan (DDA) and drug loading on the gelation time have been investigated. Gravimetric analysis, gel permeation chromatography and FTIR spectrophotometry were used to investigate the influence of the DDA and concentration of chitosan solution on hydrogel degradation. The presented results indicated that gelation time decreases by increasing Gp salt concentration, temperature, concentration and DDA of chitosan solutions, while drug loading has no significant effect on gelation time. Slower degradation profile was recorded for hydrogel with the higher DDA and concentration of chitosan in the primary solution. FTIR studies indicated that the chemical structure of chitosan macromolecules does not change significantly during the degradation. It could be concluded that biodegradation of chitosan hydrogel occurred via its surfaces.     

Novel fluoroalkyl end-capped amphiphilic diblock copolymers with pH/temperature response and self-assembly behavior

A series of fluoroalkyl end-capped diblock copolymers of poly[2-(N,N-dimethylamino)ethyl methacrylate] (PDMAEMA or PDMA) and poly[2-(N,N-diethylamino)ethyl methacrylate] (PDEAEMA or PDEA) have been synthesized via oxyanion-initiated polymerization, in which a potassium alcoholate of 4,4,5,5,6,6,7,7,7-nonafluoro-1-heptanol (NFHOK) was used as an initiator. The chemical structures of the NFHO-PDMA-b-PDEA and NFHO-PDEA-b-PDMA depended on the addition sequence of the two monomers and the feeding molar ratios of [DMA] to [DEA] during the polymerization process. These copolymers have been characterized by (1)H NMR and (19)F NMR spectroscopy and gel permeation chromatography (GPC). The aggregation behavior of these copolymers in aqueous solutions at different pH media was studied using a combination of surface tension, fluorescence probe, and transmission electron microscopy (TEM). Both diblock copolymers exhibited distinct pH/temperature-responsive properties. The critical aggregation concentrations (cacs) of these copolymers have been investigated, and the results showed that these copolymers possess excellent surface activity. Besides, these fluoroalkyl end-capped diblock copolymers showed pH-induced lower critical solution temperatures (LCSTs) in water. TEM analysis indicated that the NFHO-PDMA(30)-b-PDEA(10) diblock copolymers can self-assemble into the multicompartment micelles in aqueous solutions under basic conditions, in which the pH value is higher than the pKa values of both PDMA and PDEA homopolymers, while the NFHO-PDEA(10)-b-PDMA(30) diblock copolymers can form flowerlike micelles in basic aqueous solution.     

Biological functions of synthetic polysaccharides

Structurally well-defined polysaccharide derivatives have been synthesized via ring-opening polymerization of bicyclic anhydro sugar derivatives and via enzyme-catalyzed polymerization using phosphorylase. This article describes the following four synthetic polysaccharides, (a) Octadecylated amphiphilic polysaccharides, (b) Regiospecifically fluorinated polysaccharide, (c) Comb-shaped branched polysaccharide, (d) Graft copolymers having pendant polysaccharide chains. None of these polysaccharides could be prepared by direct chemical modifications of natural polysaccharides. The synthetic polysaccharides are useful as tools to elucidate structure-function relationships and exhibit various novel biofunctional properties.     

Chemo-physical and biological evaluation of poly(L-lysine)-grafted chitosan copolymers used for highly efficient gene delivery

For the success of non-viral gene delivery, it is of great importance to develop gene vectors with high efficiency but low toxicity. We demonstrate that PLL-grafted chitosan copolymers combine the advantages of PLL with its good pDNA-binding ability and of chitosan with its good biocompatibility. The chemo-physical properties of the prepared Chi-g-PLL copolymers are thoroughly characterized. The in vitro transfection study shows that the copolymers have a much higher gene transfer ability than the starting materials chitosan and PLL. A positive correlation between PLL chain lengths and transfection efficiency of the copolymers is found. Our results suggest that these novel Chi-g-PLL copolymers are good candidates for gene delivery in vivo.     

Synthesis and Unusual Swelling Behavior of Combined Cationic/Non‐Ionic Hydrogels Based on Chitosan

Hydrogel‐forming copolymers based on chitosan grafted with different amounts of polyacrylamide were synthesized and its swelling capacity determined in distilled water, sodium chloride solutions, as well as in buffer solutions at pH 1.2 and 8.0. The resulting products are highly efficient as hydrogel‐forming materials with swelling at equilibrium going approximately from 300 to 3 000 times the volume of the dry solid polymer in all the investigated media. The products, different to usual hydrogels, swells considerably more and quickly in electrolyte‐containing solutions compared to in distilled water. This has been attributed to their structure that contains non‐ionic polyacrylamide macromolecules grafted onto the trunk polymer chitosan, which is cationic in nature. In‐vitro drug‐release behavior of formulations containing grafted copolymers have been tested using theophylline as a water‐soluble drug and the results were compared with similar formulations containing unmodified chitosan. It was found that tablets based on formulations containing grafted chitosan show higher erosion and swelling compared with those of the matrix based on unmodified chitosan, leading to a higher fraction of theophylline released. It can be concluded that formulations based on the synthesized copolymers are potentially useful for fluid absorbency and as prolonged drug‐release matrices.

The swelling of one of the hydrogels studied here.     

Branched tetrazole-containing polymers

It has been established that the polycondensation (polyalkylation) of 5-chloromethyltetrazole occurs in a basic medium to give rise to heterochain oligomeric products. When carried out in the presence of N-H unsubstituted poly(C-vinyltetrazoles), polycondensation yields high-molecular-mass graft copolymers containing side poly(methylenetetrazole) chains. Some properties of branched polymeric products that are characterized by a high density and a large relative content of nitrogen have been studied.     

Mesoscopic patterns of block and graft copolymers in condensed systems

Equilibrium structures of two kinds of two‐component copolymers with equivalent chemical contents but with different chain architectures in bulk were compared. They are BAB triblock copolymers and AB₂ star‐branched graft copolymers. These copolymers have been confirmed to show quite different morphological change with composition. Deformation manner of B block chains of lamellar microphase‐separated BAB triblock copolymers depend on B contents, however, the volumes of the deformed coils are always kept constant to have those of the unperturbed chains irrespective of their architectures. The observed polystyrene/poly(2‐vinylpyridine) interfacial thickness is fairly thin though it is much thicker than the theoretically‐predicted one.