Interaction of poly(sodium vinyl sulfonate) and its surface graft with antithrombin III

Poly(sodium vinyl sulfonate) (PVS) was found to be 1/14 times as active as heparin in inducing the conformational change and activation of antithrombin III. The conformational change of antithrombin III was investigated in terms of the intrinsic fluorescence of tryptophan residue, the extrinsic fluorescence using 1,6-diphenyl-1,3,5-hexatriene as fluorescent probe, and Fourier-transform infrared spectroscopy. It was evident in the experiment using 2,4,6-trinitrobenzene sulfonate that PVS elicited the activity of antithrombin III by interacting with amino groups of the protein as does heparin. Sodium vinyl sulfonate was graft-polymerized onto polyetherurethane (PEU) film that was treated with glow discharge in advance. PVS-grafted PEU film adsorbed antithrombin III easily and, like ungrafted PVS, induced conformational change and activation of antithrombin III. However, the mechanism of interaction of the PVS graft with antithrombin III did not seem to be completely the same as that of ungrafted PVS in solution.     

Synthesis and nonthrombogenicity of fluoroalkyl polyetherurethanes

New polyetherurethanes carrying fluoroalkyl substituents in the side chains were synthesized from N,N-di(hydroxyethyl)heptadecafluorooctyl-sulfonamide (a chain extender), 4,4'-disocyanatodiphenylmethane, and poly(tetramethylene glycol). Various kinds of polyetherurethanes having different tensile properties were prepared by changing the content of fluoroalkyl chain extender or the molecular weight of poly(tetramethylene glycol). The surface of a film made from the fluoroalkyl polyetherurethane was strongly water-repulsive. The in vitro thrombus formation on the fluoroalkyl polyetherurethanes was reduced by increasing the content of chain extender for the same molecular weight of poly(tetramethylene glycol). Protein adsorption, platelet adhesion, and platelet activation on the fluoroalkyl polyetherurethanes were also investigated.     

Synthesis of poly(vinyl alcohol)-graft-polystyrene

The reaction of living polystyrene, prepared with butyllithium as an initiator in a tetrahydrofuran/benzene (vol. ratio 1/1 or 2/1) solution at ?30°C or ?50°C, with chlorodimethylvinylsilane was carried out to prepare polystyrene with narrow molecular-weight distribution and with a vinylsilane end group ( 1 ). The radical copolymerization of vinyl acetate with 1 in ethyl acetate solution yields poly(vinyl acetate)-graft-polystyrene ( 2 ) of controlled graft segement length. The subsequent saponification of 2 with NaOH in methanol provides poly(vinyl alcohol)-graft-polystyrene ( 3 ).     

Carboxyl-terminated poly(vinyl alcohol). Chain transfer of methyl propionate to vinyl acetate

Poly(vinyl acetate) was prepared at 60°C with benzoyl peroxide by using methyl[carbonyl-¹⁴C] propionate as chain transfer agent and solvent. The resulting polymer was hydrolysed to poly(vinyl alcohol) (PVAL) having carboxyl end groups and the average number of carboxyl groups per chain was unambiguously determined by comparing the activity of the polymer to that of the methyl propionate. An average density of 1,5 carboxyl groups per chain was found for poly(vinyl alcohol) prepared from poly(vinyl acetate) of DP 80 – 90. Other methods of end group analysis for carboxyl groups in PVAL are discussed.     

Adsorption of bovine submaxillary mucin on silicone contact lenses grafted with poly(vinyl pyrrolidone)

Bovine submaxillary mucin is considered to be an analogue of the high molecular protein present in the conjunctival mucus. This mucin was isolated from fresh salivary glands and acetylated with [1-14C]acetic anhydride. In situ adsorption of the bovine submaxillary mucin on silicone contact lenses ungrafted and grafted with poly(vinyl pyrrolidone) was performed for the first time using an original radiotracer technique. The results show that the adsorbed amounts of mucin are higher on grafted samples and that thick layers are adsorbed when mucin concentration in the bulk solution is increased. Desorption experiments reveal that in addition to the tightly adsorbed protein layer, a loosely bound mucin layer of the same thickness exists on grafted and ungrafted silicones.     

Synthesis of poly(vinyl alcohol)/poly(dimethylsiloxane) graft copolymer

Poly(vinyl acetate)/poly(dimethylsiloxane) graft copolymer ( 4a ), with a controlled poly(dimethylsiloxane) graft chain length, was synthesized by radical copolymerization of vinyl acetate with poly(dimethylsiloxane) ( 3 ) having a dimethylvinylsilyl end group. 3 was prepared by living anionic polymerization of hexamethylcyclotrisiloxane ( 1 ) with butyllithium and subsequent termination with chlorodimethylvinylsilane ( 2 ). Poly(vinyl alcohol)/poly(dimethylsiloxane) graft copolymer ( 4b ) was then synthesized by selective saponification of the poly(vinyl acetate) segments in the graft copolymer 4a with K₂CO₃ in methanol.     

Synthesis of poly(vinyl ether)s with perfluoroalkyl pendant groups

2-Perfluoro(alkyl)ethyl vinyl ethers, F(CF₂)_nCH₂CH₂OCH?CH₂, (n = 6 or 8), were synthesized and polymerized by means of cationic initiators (HI/ZnI₂ and CF₃SO₃H/(CH₃)₂S). The perfluorohexyl-substituted poly(vinyl ether) is completely amorphous. The polymer with perfluorooctyl segments shows side chain crystallization with a disordering transition. For the corresponding perfluorooctyl monomer a liquid-crystalline phase was observed before melting. Copolymerization experiments of the flurocarbon-segmented monomers with a vinyl ether containing a cyanobiphenyl group in the side chain did not give homogeneous copolymers. This is attributed to the slower rate of polymerization of the fluorinated vinyl ethers as compared with the liquid-crystalline comonomer.     

Synthesis and swelling-deswelling kinetics of poly(N-isopropylacrylamide) hydrogels grafted with LCST modulated polymers

Two types of thermo-responsive hydrogels are synthesized to obtain comb-type grafted gels with different lower critical solution temperatures (LCSTs) between graft chains and cross-linked backbone networks: these are poly(N-isopropylacrylamide) (PIPAAm) cross-linked hydrogels grafted with poly(N-isopropylacryl amide-co-N,N-dimethylacrylamide) (poly(IPAAm-co-DMAAm)) maintaining a freely mobile end and poly(IPAAm-co-DMAAm) cross-linked hydrogels grafted with PIPAAm chains. The effect of graft chain hydrophilic/hydrophobic balance as well as its mobility on deswelling kinetics of these grafted gels are investigated through the polymer LCST modulation and external temperature changes. The deswelling rate of poly(IPAAm-co-DMAAm)-grafted PIPAAm gel increases with increasing in temperature. This gel shows a discontinuous increase of the deswelling rate when the temperature is applied from below to above the graft chain LCST (37 degrees C). The deswelling rate of PIPAAm-grafted poly(IPAAm-co-DMAAm) gel increases continuously when the temperature is applied from below to above the graft chain LCST (31 degrees C). Due to the strong hydrophilicity of backbone network, the hydrophobic aggregation force weak. In contrast to the graft-type gels, normal-type poly(IPAAm-co-DMAAm) cross-linked gel without graft chains demonstrates the discontinuous decrease for the deswelling rate when the temperature is applied from below to above the polymer LCST (36 degrees C), entrapping water inside the gel due to the formation of an impermeable dense skin layer at the gel surface. These gel deswelling mechanisms are discussed in terms of gel structures.     

Synthesis and swelling-deswelling kinetics of poly(N-isopropylacrylamide) hydrogels grafted with LCST modulated polymers

Two types of thermo-responsive hydrogels arc synthesized to obtain comb-type grafted gels with different lower critical solution temperatures (LCSTS) between graft chains and cross-linked backbone networks: these are poly(N-isopropylacrylamide) (PIPAAm) cross-linked hydrogels grafted with poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (poly(IPAAm-(-o-DMAAiii)) maintaining a freely mobile end and poly(IPAAm-co-DMAAm) cross-linked hydrogels grafted with PIPAAm chains. The effect of graft chain hydrophilic/hydrophobic balance as well as its mobility on deswelling kinetics of these grafted gels are investigated through the polymer LCST modulation and external temperature changes. The deswelling rate of poly(IPAAm-co-DMAAm)-grafted PIPAAm gel increases with increasing in temperature. This gel shows a discontinuous increase of the deswelling rate when the temperature is applied from below to above the graft chain LCST (37°C). The deswelling rate of PIPAAm-grafted poly(IPAAm-co-DMAAm) gel increases continuously when the temperature is applied from below to above the graft chain LCST (31°C). Due to the strong hydrophilicity of backbone network, the hydrophobic aggregation force weak. In contrast to the graft-type gels, normal-type poly(IPAAm-co-DMAAm) cross-linked gel without graft chains demonstrates the discontinuous decrease for the deswelling rate when the temperature is applied from below to above the polymer LCST (36°C), entrapping water inside the gel due to the formation of an impermeable dense skin layer at the gel surface. These gel deswelling mechanisms are discussed in terms of gel structures.     

Synthesis of poly(vinyl alcohol)-graft-poly(tetrahydrofuran)

The reaction of a living poly(tetrahydrofuran) (poly(THF)), prepared with methyl trifluoromethanesulfonate as an initiator, with 3-sodiopropoxydimethylvinylsilane was carried out to produce a uniform poly(THF) macromonomer with a vinylsilane end-group. Poly(vinyl acetate)-graft-poly(THF) of controlled graft segment length was then synthesized through radical copolymerization of this poly(THF) macromonomer with vinyl acetate. The subsequent saponification with NaOH in methanol provided poly(vinyl alcohol)-graft-poly(THF).     

Chromophoric poly(vinyl alcohol derivative)s, 1. Synthesis and spectroscopical characterization of some poly(vinyl alcohol)s with alkoxyazobenzenecarbonyl substituents

The synthesis of new poly[(vinyl 4′-alkoxyazobenzene-4-carboxylate)-co-(vinyl alcohol)]s 4a–c by Einhorn esterification of poly(vinyl alcohol) with 4′-alkoxyazobenzene-4-carbonyl chlorides 3a–c prepared in two steps from 4′-hydroxyazobenzene-4-carboxylic acid ( 1 ) is described. The degree of esterification is found to be about 85 mol-%. Infrared, ¹H and ¹³C nuclear magnetic resonance and ultraviolet spectroscopical data of the obtained polymers are determined.     

Synthesis of novel sulfonyl-containing liquid-crystalline side-chain poly(vinyl ethers)

The synthesis of some new liquid-crystalline polymers with sulfonyl-containing mesogenic groups is described. 4-[(S)-(-)-2-MethylbutyIsulfonyl]-4′-[(11-vinyloxy)undecyloxy]biphenyl ( 10 -11), 4-[(S)-(-)-2-methylbutylsulfonyl]-4′-[8-(vinyloxy)octyloxy]biphenyl ( 10 -8), 4-[(S)-(-)-2- methylbutylsulfonyl]biphenyl 4-[11-(vinyloxy)undecyloxy]benzoate ( 12 -11), 4-[(S)-(-)-2-methylbutylsulfonyl]biphenyl 4-[8-(vinyloxy)octyloxy]benzoate ( 12 -8), 4-[(S)-(-)-2-methylbutyloxy]-4′- [11-(vinyloxy)undecylsulfonyl]biphenyl ( 18 -11) and 2-[11-(vinyloxy)undecyloxy]-6-{4-[(S)-(-)-2- methylbutylsulfonyl]phenyl}naphthalene ( 23 -11) were all synthesized, and polymerized with the initiating system CF₃SO₃H/S(CH₃)₂ in CH₃Cl₃ at 0°C. Monomers 10 -11, 10 -8, 18 -11 and 23 -11 are crystalline, while both 12 -11 and 12 -8 show an enantiotropic smectic A phase. All polymers exhibit the same thermotropic behaviour as their corresponding monomers, except poly( 23 -11) which exhibits an enantiotropic smectic A (s_A) and a monotropic chiral smectic C phase (S*_C).     

Synthesis and nonthrombogenicity of polymer membrane with surface-graft polymers carrying thrombin inhibitor.

An acrylamide derivative of a thrombin inhibitor was synthesized and graft polymerized to the surfaces of polymer membranes. The thrombin-inhibitor activity was unaffected by the introduction of an acryloyl group. The surface-graft membrane deactivated thrombin markedly and suppressed adhesion of platelets, resulting in a high nonthrombogenicity. Immersion of polymer membranes blended with the thrombin inhibitor in phosphate-buffered saline for 10 d resulted in the loss of nonthrombogenicity, while the polymer membranes grafted with the thrombin inhibitor derivative maintained the nonthrombogenicity over a long period.     

Conformational change of poly(L-lysine) by formation of complexes with poly(styrene sulfonate)

Circular dichroic studies were made on the conformational change of poly(L -lysine) (PLL) by complex formation with sulfonated polystyrenes (PSS) as functions of pH, temperature and polymer compositions in comparison with the complexes of PLL with sulfated poly(vinyl alcohol) (PVS). The coil-to-helix transition of PLL by complex formation at neutral and acidic pHs, which took place in the PLL/PVS (with high degrees of sulfation) complexes, was prevented in the PLL/PSS complexes due to the less chain flexibility of PSS than PVS. Above pH 11, the α-helix of PLL was partially broken into random coil by complex formation with PSS. The drastic decrease in the solution viscosity by the complex formation revealed a large contraction of PSS chain and subsequently a large strain of the α-helical PLL chain so as to give the breakdown of the α-helix. This is denoted a strain-induced conformational change of PLL. It was found that the α-helix of PLL was thermally stabilized by the complex formation with PSS as in the case of PLL/PVS complexes. A β-to-α transition of PLL by the complex formation with PSS was also found, while the β-form was maintained in the PLL/PVS (with high degrees of sulfation) complexes.     

Synthesis,surface properties and performance of thiosulphate-substituted plasticized poly(vinyl chloride)

Plasticized poly(vinyl chloride) (PVC) was surface modified by nucleophilic substitution of the chlorine atoms of PVC by thiosulphate in aqueous media in the presence of a phase-transfer catalyst. The properties of the modified surface were evaluated by contact angle measurements, attenuated total reflection Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and scanning electron microscopy. Migration of the plasticizer di-(2-ethylhexyl) phthalate from control as well as modified PVC was examined in hexane, in cottonseed oil and in poly(ethylene glycol)-400 (PEG-400). While the modified PVC was found to be highly migration resistant in hexane, cottonseed oil and PEG-400 extracted the plasticizer. The modified PVC was found to cause haemolysis and was cytotoxic. A possible explanation for the difference in performance of the modified material in different extraction media and its toxicity is presented from a mechanistic view of the substitution process.     

Synthesis of poly(vinyl alcohol) having a thiol group at one end and new block copolymers containing poly(vinyl alchohol) as one constitent

Poly(vinyl alcohol) (PVA) and poly(vinyl acetate) having a thiol group at one end were synthesized by free-radical polymerization of vinyl acetate in presence of thioacetic acid as a chain transfer agent followed by treating with sodium hydroxide/methanol and ammonia, respectively. It was found that block copolymers containing the PVA sequence as one constituent were obtained by the redox-initiated polymerization of some vinyl monomers, for example, acrylic acid (AA) and acrylamide (AAm), using PVA having a thiol end group as reductant and an oxidant such as potassium bromate and potassium persulfate.     

Biostability and blood-contacting properties of sulfonate grafted polyurethane and Biomer

Sulfonate-containing polyurethanes were evaluated for in vivo biodegradation using subcutaneously implanted tensile bars. In addition, these anionically charged polyurethanes were evaluated for in vivo activation of human complement C3a and ex vivo platelet deposition in arteriovenouslyshunted canines. The sulfonate derivatized polymers included laboratory synthesized polyurethane and Biomer. Other polymers used for references included Intramedic^TM polyethylene, Silastic^TM and a poly(ethylene oxide) based polyurethane. The biodegradation results indicated that Biomer and the laboratory sulfonated Biomer (both manufactured with stabilizers), remained mechanically stable, retaining both tensile strength and elasticity after 4 weeks of subcutaneous implantation. The unstabilized polyurethanes (with or without sulfonation), however, showed marked cracking and a loss of mechanical properties after the same period of subcutaneous implantation. Sulfonated polyurethanes depressed human complement C3a activation in plasma, as indicated by decreased levels of anaphylatoxin production. The results of canine ex vivo blood contacting experiments were conducted in both an acute and chronic model and demonstrated decreased platelet deposition and activation for the sulfonated polyurethanes.     

Synthesis and liquid crystalline properties of azobenzene-containing poly(vinyl ether)s with narrow molar mass distribution

A series of new liquid crystalline (LC) poly(vinyl ether)s with different molar masses was synthesized via a two-step procedure involving the preparation of functional matrices by living cationic polymerization of an ω-chloroalkyl vinyl ether monomer followed by a grafting reaction of an azobenzene mesogenic unit onto them. By appropriately adjusting the experimental conditions, it was possible to predetermine the molar mass characteristics of the LC polymers. Each of the parent and modified poly(vinyl ether)s had a narrow molar mass distribution. The LC polymers were semicrystalline and formed a nematic mesophase, enantiotropic or monotropic in character. The transition temperatures increased with increasing molar mass up to a limiting value and then remained nearly constant. Accordingly, poly(vinyl ether)s with predetermined molar mass and narrow molar mass distribution could be prepared.     

Synthesis and evaluation of water soluble pH sensitive poly (vinyl alcohol)-doxorubicin conjugates

The accuracy of spatiotemporal control cargo delivery and release are primordial to enhance the therapeutic efficiency and decrease the undesirable effects, in this context a novel prodrug were developed based on biocompatible polyvinyl alcohol (PVA) substrate. PVA was conjugated to doxorubicin (PVA-DOX) via an acid-labile hydrazone linkage. PVA was first functionalized with acidic groups, then reacted with hydrazine hydrate to form an amide bond. The amine group of PVA hydrazide was linked to carbonyl group (C = O) of DOX to form a pH sensitive hydrazone bond. The molecular structure of the PVA-DOX was confirmed by FTIR, XPS, and ¹H-NMR analysis methods. The degree of grafting were evaluated by TGA and confirmed by XPS, which reveals the successful bond attachment of DOX to PVA. Our findings confirm pH dependent DOX release from PVA-DOX prodrug with faster release rate in acidic environment (pH 5.0, pH 6.0) and slower release rate in neutral pH environment (pH 7.4). Compared to the primary DOX, our synthesized PVA-DOX conjugates could exhibit a promising therapeutic effect, high biocompatibility and zero premature release. The results prove the successful synthesis of PVA-DOX conjugates with high efficiency.