Molecular design of biodegradable functional polymers, 4 Poly(vinyl alcohol) block as biodegradable segment

The minimum structure of a poly(vinyl alcohol) block as a biodegradable segment in the polymer chain was estimated with respect to block length and its stereochemical configuration. It was found that poly(vinyl alcohol) block with a chain length of more than 3 monomeric units and having an isotactic structure is quickly biodegraded, in contrast to an atactic block having the same chain length, by poly(vinyl alcohol) (PVA) assimilating microbes and PVA-dehydrogenase. It was also found that the substrate specificity of PVA-dehydrogenase obtained from both Alcaligenes faecalis KK314 and Pseudomonas sp. 113 P3 is quite similar.     

Molecular design of biodegradable functional polymers, 5. Enzymatic degradation of polycarboxylates containing vinyl alcohol blocks as biodegradable segment

Poly(sodium carboxylate)s containing vinyl alcohol blocks were prepared, and their microbial degradability and the poly(vinyl alcohol) (PVA) dehydrogenase activity as a function of vinyl alcohol block length in the polymer chain were analyzed. A clear relationship between the biochemical oxygen demand (BOD) biodegradability using the activated sludge and the relative activity of PVA dehydrogenase of a PVA-assimilating strain, Alcaligenes faecalis KK314, was observed. A vinyl alcohol block length of about 7 monomer units corresponds to the minimum chain length of the vinyl alcohol block length which acts as a biodegradable segment in the poly[(disodium fumarate)-co-(vinyl alcohol)]. The enzymatic cleavability of polycarboxylates containing vinyl alcohol blocks was estimated using the cell-free extracts of a PVA-assimilating microbial strain, A. faecalis KK314, as the PVA-cleaving enzyme source for both PVA dehydrogenase and hydrolase. The molecular weight of the polycarboxylates was reduced depending on the vinyl alcohol block length, and a similar molecular weight reduction tendency was observed with respect to the BOD values and PVA dehydrogenase activities.     

Behaviour of permeation and separation for aqueous organic acid solutions through poly(vinyl chloride) and poly[(vinyl chloride)-co-(vinyl acetate)] membranes

The permeation and separation characteristics of poly(vinyl chloride) (PVC) and poly[(vinyl chloride)-co-(vinyl acetate)] (poly(VC-co-VAc)) membranes were investigated for aqueous organic acid solutions by pervaporation and evapomeation. The PVC membrane preferentially incorporates organic acids and predominantly permeates water from aqueous organic acid solutions. Water permselectivities of these aqueous solutions through the PVC membrane are significantly dependent on high diffusivity of water across the membrane. It was found that the permeation rate increases and the separation factor for the water permselectivity decreases with increasing vinyl acetate (VAc) content in the poly(VC-co-VAc) membrane. Preferential solubility of acetic acid into the poly(VC-co-VAc) membrane increases with the VAc content. This result was explained by a strong affinity between acetic acid and the VAc unit in the poly(VC-co-VAc) membrane.     

Hydrogen-bond interactions between poly[(ethyl acrylate)-co-(acrylic acid)] and polycyanate derived from bisphenol A dicyanate

Polycyclotrimerization of aromatic dicyanate (i. e. bisphenol A dicyanate, BPADCy) produces a polycyanate network with s-triazine rings as crosslinking points. In this study, different amounts of poly-[(ethyl acrylate)-co-(acrylic acid)] (PEAc) were mixed with BPADCy, and heated to generate PEAc-modified polycyanates. In contrast to the usual two-phase thermoplastic-modified polycyanates, the PEAc-modified polycyanates are single-phase in nature (according to results of optical microscopy and scanning electron microscopy). The miscibility between linear PEAc and thermosetting polycyanate is due to hydrogen-bonding (H-bonding) between carboxylic acid groups in PEAc and s-triazine rings in polycyanate. This H-bond interactions can be verified by infrared spectroscopy using the —OH, —C=O, and —C=N stretching modes in PEAC/BPADCy mixtures at different temperatures. Infrared spectroscopy on model compound mixtures (succinic acid/BPADCy) was also conducted to confirm the H-bond interactions between cyanate groups and —COOH groups.     

Porosity determination of poly[(trimethylolpropane trimethacrylate)-co-(methyl methacrylate)] gels

In this paper we studied the influence of the copolymerization of trimethylolpropane trimethacrylate (TRIM) with methyl methacrylate (MMA) on the pore structure of the resulting gels. TRIM and MMA were suspension-copolymerized with toluene as pore-forming agent. All gels have bimodal pore-size distributions. The size distribution of large pores (r > 50 Å) of the solvent-free poly(TRIM-co-MMA) broadens when the TRIM/MMA ratio decreases. The size distribution of small pores (r < 50 Å) shows sharp maxima for pores with a radius of 20 Å. In the swollen state the separation range for the poly(TRIM-co-MMA) particles of polystyrene standards varies with the TRIM/MMA ratio. The results of the porosity measurements of the swollen gels show good agreement with the results obtained from the dry gels. The porosity of the dry gels was studied with scanning electron microscopy, nitrogen adsorption/desroption and mercury porosimetry. The pore-size distributions of the swollen poly(TRIM-co-MMA) gel particles were calculated from the size-exclusion chromatography (SEC) results.     

Polymeric photosensitizers, 1. Synthesis and photochemical properties of poly[(sodium p-styrenesulfonate)-co-(4-vinylbenzyl chloride)] containing rose bengal chromophores

The new polymeric photosensitizer poly[(sodium p-styrenesulfonate)-co-(4-vinylbenzyl chloride/rose bengal)] for singlet oxygen production in aqueous solutions was synthesized and studied. The polymer contains rose bengal (4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein) chromophores covalently attached to the polymer chain. The quantum yield of singlet oxygen formation by the polymer-bound chromophore was found tobe close to that determined for free rose bengal. The polymer has been shown to photosensitize oxidation reactions in aqueous media.     

Radiation processed hydrogel of poly (vinyl alcohol) with biodegradable polysaccharides

Poly(vinyl alcohol) (PVA) can be modified to polymer hydrogels by radiation crosslinking and can be used in different biomedical applications. A study was done on the optimization of ingredients concentration for preparing good quality PVA hydrogels with natural polysaccharides. The synthesized hydrogels were also characterized by measuring the different physical properties e.g. gel fraction, swelling and absorption rate. Besides these, sterility test were also performed. Good quality hydrogels were obtained from PVA and natural polysaccharides solutions with 27 kGy radiation dose. There is an influence of natural polysaccharides on the gel fraction of hydrogel. The increase in the amount of polysaccharide causes a decrease in gel fraction that is decrease in the crosslinking density of PVA hydrogel network. The prepared hydrogels were found to be sterile.     

Modification of poly[(3-hydroxybutyric acid)-co-(3-hydroxyvaleric acid)] film surfaces in an oxygen low pressure plasma

Poly[(3-hydroxybutyric acid)-co-(3-hydroxyvaleric acid)] (91:9 mass-%) (P(HB-co-9% HV)) film surfaces were modified by an oxygen plasma treatment (75 W, 50 Pa, 5 min). The number of oxygen atoms increases about 12–13% and the polar component of the surface energy increases from 6.3 to 21 mN · m^?1. However, the wettability is stable only after 60 days. Untreated and treated film surfaces are studied by means of X-ray photoelectron spectroscopy with two different depth analyses. With storage time, the oxygen contents of the modified film is constant at a take-off angle of 20° but decreases to the initial value at a take-off angle of 70°. The superficial layer of the polymer film between the top of the film to a depth of 10 nm is divided into three superimposing zones. The interpretation is supported by motions of modified macromolecular chains and buried polar groups, chain cleavage and the formation of low-molecular-weight molecules which leads to a decrease of the glass transition temperature (plasticizer effect) and migration of short chains from the lowest modified zone toward the surface.     

Network parameters and scaling behaviour of chemically crosslinked hydrogels of poly[(N,N-dimethylacrylamide)-co-(methyl methacrylate)]

Copolymerization of N,N-dimethylacrylamide (DMA) with methyl methacrylate in both the presence and absence of ethylene dimethacrylate (EDMA) was effected to very high conversion by γ-irradiation. The resultant xerogels were swollen to equilibrium in water at five specific temperatures within the interval 280.2–338.2 K. The volume fractions of the polymer ?₂ in the hydrogels were determined from the measured dimensions, and compression-strain measurements yielded the polymer-water interaction parameter, the effective crosslinking densities, and Young's moduli Y. The observed dependence of these parameters on copolymer composition and content of EDMA is discussed. A scaling law of the form Y ∝ ? is obeyed well by hydrogels of xerogels containing 80 wt.-% DMA (r = 2.37 ± 0.10) and moderately well by hydrogels of xerogels with only 50 wt.-% DMA (r = 2.54 ± 0.10).     

Sequence analysis and comonomer interactions in poly[(4-chlorophenyl methacrylate)-co-(methyl methacrylate)]s

Copolymers of 4-chlorophenyl methacrylate and methyl methacrylate were prepared and investigated by ¹H and ¹³C NMR spectroscopy. The copolymer composition, determined by chlorine analysis, ¹H and ¹³C NMR, was found to be close to the initial composition of the monomer mixture. The sequence analysis was carried out by analyzing the methoxy signals of the ¹H NMR spectra. Six out of ten tactic and compositional triads could be resolved. It was found that the copolymers are predominantly syndiotactic and the compositional and tactic triad populations are given. The aromatic carbon atoms are sensitive towards compositional and tactic sequence effects, which results in a switch of the order of the tactic signals at different aromatic carbon atoms.     

Kinetics of the polymer-analogous reaction of poly[(methyl methacrylate)-co-(methacrylic acid)] with epichlorohydrin

Poly[(methyl methacrylate)-co-(glycidyl methacrylate)] (poly(MMA-co-GMA)) was obtained by polymer-analogous reaction of poly[(methyl methacrylate)-co-(methacrylic acid)] with an excess of epichlorohydrin (ECH) in the presence of a quaternary ammonium salt R₄NX as catalyst. The kinetics of the addition reaction and the consecutive transepoxidation reaction was studied at 50–90°C. The rate constant of the addition reaction is one order of magnitude higher with E₁ = 71 kJ · mol^?1 than that of the transepoxidation reaction with E₂ = 83 kJ · mol^?1. The rate constants rise linearly with increasing concentration of the catalyst R₄NX. The equilibrium constants K ≈ 2,3 of transepoxidation of glycidyl methacrylate (GMA) as well as of poly(MMA-co-GMA) both with 1,3-dichloropropane-2-ol were determined in butyl acetate and dimethylformamide as solvent at 80–100°C. During the reverse transepoxidation reaction of 3-chloro-2-hydroxypropyl methacrylate (CHPM) as well as of its MMA-copolymer with equimolar amounts of ECH, side products were formed from the beginning of the reaction and the equilibrium was not established. The addition of ECH to CHPM was observed as a side reaction.     

Molecular design of biodegradable functional polymers, 2 Poly(carboxylic acid) containing xylopyranosediyl groups in the backbone

Polymer 2 , containing unreacted xylopyranosediyl groups in the backbone, was prepared from xylan by the conversion of vicinal hydroxyl groups to carboxylic groups using periodic acid/sodium chlorite. 2 was found to be biodegraded quickly by the activated sludge. Arthrobacter sp. KM810 and Flavobacterium sp. KM811 were isolated as 2 -degrading strains. It was found that these strains biodegraded all molecular-weight fractions of 2 . 2 shows a good calcium sequestration capacity which is comparable to that of poly(sodium acrylate).     

XPS analysis of poly[(3-hydroxybutyric acid)-co-(3-hydroxyvaleric acid)] film surfaces exposed to an allylamine low-pressure plasma

Homogeneous and stable layers were deposited through allylamine plasma polymerization (75 W, 100 Pa, 15 min) onto poly[(3-hydroxybutyric acid)-co-(3-hydroxyvaleric acid)] (91 : 9 wt.-%) (P(HB-co-9%HV)) film surfaces, XPS analysis using take-off angles of 20° and 70° and performed 10 days and 20 days after plasma treatment gives information on the composition (in atom%) of the modified surface: C, 62.74; N, 19.60; O, 17.65. The unexpected oxygen percentage is weaker if argon plasma pretreatment (25 W, 40 Pa, 5 min) is applied. Then, a succinct mechanism is proposed. The study of changes in element ratios and binding energy values shows that the majority of incorporated functional groups seem to be amide and imine groups.     

Structural and functional characterisation of poly(vinyl alcohol) and heparin hydrogels

Synthetic scaffolds show great promise for use in tissue engineering due to their ability to mimic some aspects of the extracellular matrix, however, their use has been hindered by the lack of inherent recognition sites that are required for protein and cell interactions. Heparan sulfate (HS), a glycosaminoglycan polysaccharide present in the basement membrane and on the cell surface, binds growth factors and cytokines and enhances the signalling of these ligands by forming complexes with their receptors. This study focuses on the formation of photopolymerised hydrogels derived from methacrylated macromers of poly(vinyl alcohol) (PVA) and heparin, with the aim of imparting the growth factor activation property of heparin to the synthetic scaffolds. It was shown that the methacrylate group attachment on heparin did not result in the fragmentation of heparin molecules, and that the biological activity of the methacrylated heparin was preserved as determined by tests on its anticoagulation properties and ability to signal fibroblast growth factor-2 (FGF-2). The addition of heparin into the PVA hydrogels resulted in an increase in mass swelling ratio from 5.8 for pure PVA to 6.5 and 6.6 for PVA/heparin co-hydrogels of 19/1 and 17.5/2.5 (w/w) compositions, respectively. It is believed that heparin molecules can be added into a synthetic PVA scaffold without adversely affecting the structural and mechanical stability of the PVA scaffold. The tensile moduli of the co-hydrogels remained close to that of PVA hydrogels (61 kPa), even up to 2.5% heparin composition (PVA/hep 17.5/2.5). Finally, the co-hydrogels were found to retain the growth factor signalling activity of heparin at equilibrium.     

Study of the compatibility of poly[styrene-co-(cinnamic acid)]/poly[(ethyl methacrylate)-co-(2-dimethylaminoethyl methacrylate)] blends

Compatibilization of an immiscible polymer pair, polystyrene and poly(ethyl methacrylate), is achieved by introducing along the polymer chains cinnamic acid and 2-dimethylaminoethyl methacrylate groups, respectively. The miscibility behavior of a series of poly[styrene-co-(cinnamic acid)] (PSCA) copolymers containing 5, 8, and 23 mol-% of acidic units, with poly[(ethyl methacrylate)-co-(2-dimethylaminoethyl methacrylate)] (PEMADAE) was investigated by DSC and FTIR. Based on the single composition-dependent glass transition criterion, each PSCA copolymer is miscible with PEMADAE over the three blend compositions studied. The glass transition temperatures are higher than predicted according to the additivity principle. This indicates the occurrence of strong intermolecular interactions between the polymeric chains of the two components. The T_g-composition curves of the investigated systems are interpreted according to the Kwei and the Schneider approaches. The results of the FTIR study reveal that the changes detected in the carbonyl stretching frequency region are the consequence of hydrogen bonding between the carboxylic acid groups in PSCA and the carbonyl groups in PEMADAE.     

Infrared analysis on blends of poly(3-hydroxybutyric acid) and stereoregular poly(vinyl alcohol): influence of tacticity of poly(vinyl alcohol) on crystallization of poly(3-hydroxybutyric acid)

The extens of crystallization of poly(3-hydroxybutyric acid) (P(3HB)) in blends of P(3HB) with stereoregular poly(vinyl alcohol) (PVA) have been studied by means of infared spectroscopy. The degree of crystallinity of P(3HB) was found to decrease by blending with atactic PVA when PVA was the predominant component of the blend. In P(3HB) blends with highly syndiotactic PVA, a significant suppression of P(3HB) crystallization was observed in a wider range of blend composition than that in P(3HB)/atactic PVA blends. These results are consistant with previous results obtained by means of solid-state ¹³C nuclear magnetic resonance and differential scanning calorimetry. In blends with highly isotactic PVA, P(3HB) was found to crystallize in the same way as in pure P(3HB).     

Hydrogels for site-specific oral delivery. Poly[(acrylic acid)-co-(butyl acrylate)] crosslinked with 4,4′-bis(methacryloylamino)azobenzene

Copolymers of acrylic acid and butyl acrylate crosslinked with 4,4′-bis(methacryloylamino)-azobenzene were synthesized by radical copolymerization with different amounts of acrylic acid and crosslinker. They were characterized by equilibrium degree of swelling, modulus of elasticity in compression at pH 2 and 7, and effective network density. The acido-basic properties of crosslinked copolymers were compared with linear (soluble) ones of the same composition. The study of the dependence of the apparent dissociation constant (pK_app) on the degree of dissociation has shown that conformational transition from the compact to the random conformation of the polymeric chains occurs only in crosslinked copolymers. The high values of pK_app obtained indicate that strong Donnan effects and low polarity of environment of carboxy groups are operative in acido-basic equilibria.     

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.     

Functional poly[(ethylene oxide)-co-(β-benzyl-L-aspartate)] polymeric micelles: block copolymer synthesis and micelles formation

Well-defined α-methoxy-ω-amino and α-hydroxy-ω-amino poly(ethylene oxides) (PEOs), obtained by chemical modifications of α-hydroxy-ω-amino PEO, were studied for block copolymerization with β-benzyl-L -aspartate-N-carboxy anhydride (BLA-NCA); the block copolymers were obtained via polymerization of BLA-NCA with the primary amino end-groups of the PEOs as initiator in the mixture CHCl₃/N,N-dimethylformamide (DMF) (vol. ratio10/1). Gel-permeation chromatography (GPC) of both block copolymers showed the presence of BLA oligomers. α-Methoxy PEO/PBLA and α-hydroxy PEO/PBLA block copolymers were submitted to selective precipitation in 2-propanol; this method allowed total elimination of oligomers as shown by GPC of the purified block copolymers. Moreover, for each block copolymer, the number of BLA units determined by ¹H NMR spectroscopy (in CDCl₃) was in good agreement with the number calculated from the ratio BLA-NCA/amino end-groups of PEO. The polymeric micelles having hydroxy functions or methoxy groups on the outer-shell were prepared by dialysis against water of the corresponding solution of the pure block copolymers. These polymeric micelles were characterized by dynamic light scattering (diameter) and by fluorescence spectroscopy (critical micellar concentration, cmc) using pyrene as a fluorescence probe. Both polymeric micelles have a small diameter (<50nm) and a very low cmc (<20 mg/L in water).     

Interaction between poly(L-lysine) and sulfated poly(vinyl alcohol)

Ionic polymer-polymer interaction was studied in aqueous solution for poly(L -lysine) (PLL) and sulfated poly(vinyl alcohol) (PVS) as functions of pH, the degree of sulfation, the functional unit mole ratio of the two polymers and temperature by means of circular dichroism and viscosity measurements. In all the cases studied, strong inter-polymer complexes were formed at the functional unit mole ratio (VS)/(LL) higher than 1. Although PLL itself is well known to take the α-helical conformation at such a high pH as 11, the PLL conformation in the PLL/PVS complexes did not depend on pH but on the degree of sulfation: at room temperature, PLL took random coil conformation in PLL/PVS-25 (25: degree of sulfation in mole-%) and PLL/PVS-30, and the α-helical conformation (helicity of 70%) in PLL/PVS-46 and PLL/PVS-95. Models for the complex structures are postulated. Methanesulfonic acid did not influence the conformational transition of PLL, supporting that a polymer effect took place in the complex formation between PLL and PVS. Thermal effect on the PLL conformation in the complex is also discussed.