Characterization of poly[di(carboxylatophenoxy)-phosphazene] by an aqueous gel permeation chromatography

A water-soluble phosphazene polyelectrolyte, poly[di(carboxylatophenoxy)phosphazene] (PCPP), was characterized using aqueous gel-permeation chromatography (GPC) with concentration (UV and RI) and molecular weight sensitive (multiangle laser light-scattering) detectors. Agreement was observed between the weight-average molecular weights determined by GPC with a light-scattering detector, conventional GPC using fractionated narrow PCPP standards, and also by static light-scattering measurements. The effect of chromatography conditions, such as ionic strength of the mobile phase, column resolution, and injection volume was investigated. Mark–Houwink constants of PCPP in aqueous solution (phosphate buffer, pH 7.4, 0.42MNaCl) were determined. The validity of the universal calibration curve and the occurrence of a secondary nonexclusion mechanism of separation in aqueous GPC of phosphazene polyelectrolytes are discussed. © 1996 John Wiley & Sons, Inc.     

Molecular Simulations of Polyphosphazenes for Biomedical Applications

Properties of four biomedically relevant polyphosphazenes—poly(dichlorophosphazene) (PDCP), poly(glycineethylesterphosphazene) (PGEEP), poly[bis(carboxylatophenoxy)phosphazene] (PCPP) and poly[di(imidazole)phosphazene] (PDIP)—were investigated by molecular dynamics simulations. The densities obtained for these polymers ranged from 1.269 (PGEEP) to 2.174 (crystalline PDCP)?g/cm³. As validation of the simulation results, the glass transition temperature of PGEEP was estimated to be 255?K, in agreement with experimental results. Radial distribution functions showed evidence of hydrogen bonding in amorphous PCPP, but little or no hydrogen bonding was observed in the remaining polymers. Hydrogen bonding leads to increased electrostatic interactions in amorphous PCPP, as evidenced by the larger solubility parameter of 19.082?(J/cm³)^1/2 obtained for PCPP compared to 14.437, 13.928, and 14.647?(J/cm³)^1/2 for amorphous PDCP, PGEEP and PDIP, respectively. Time-correlation functions were calculated for each polymer to determine the relative flexibility of the backbones and side-groups of each polyphosphazene. The backbones and side-groups of both amorphous PDCP and PGEEP show significant flexibility while those of amorphous PCPP and PDIP show more limited motions.     

Polyphosphazene microspheres: Preparation by ionic complexation of phosphazene polyacids with spermine

Polyphosphazene polyacids are potent immunostimulating compounds. Formulation of these water‐soluble macromolecules into a microparticulate form can extend their utility in vaccine delivery applications. A simple method for the preparation of microspheres and nanospheres using polyphosphazene polyacids is reported. The key element of the process is ionic complexation of polyphosphazenes in aqueous solutions with physiologically occurring amines, such as spermine. A phase diagram of poly[di(carboxylatophenoxy)phosphazene] (PCPP)–spermine–water system is established, which shows an extensive area of microsphere formation. Microsphere size distribution is studied as a function of reaction conditions and concentrations of reactants. This method can be applied to polyphosphazene polyacids containing carboxylic acid and sulfonic acid functionalities and can be used for protein encapsulation. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 414–419, 2006     

Poly[bis(m-chlorophenoxy)phosphazene]. Macromolecular characterization and degradation studies

The macromolecular structures of five poly[bis(m-chlorophenoxy)phosphazene] samples are critically analyzed. There are significant variations in the solubility behavior and physical properties of the polymers. Property differences are attributed mainly to the incomplete nucleophilic substitution of the dichlorophosphazene polymer precursor. All the polymers are found to have high molecular weights and broad, bimodal molecular weight distributions. However, differences in branching are noted and the presence of thermally labile “weak links” on the polymer chain backbones is suspected. At 165°C in static air, the polyphosphazene degrades by a random degradation mechanism and for long exposure times is considerably more stable than polystyrene.     

The Biocompatibility of Biodegradable Glycine Containing Polyphosphazenes: A Comparative study in Bone

Polyphosphazenes have gained considerable attention as biomaterials for use in tissue engineering and orthopaedic reconstruction. In this paper we examined the polyphosphazenes’ in vivo biocompatibility and degradation by studying their ability to repair bone in a rabbit metaphyseal distal femur defect model. Matrices constructed from poly[(50% p-methylphenoxy)-(50%ethyl glycinato) phosphazene] (PPHOS-50) and poly[bis(ethyl glycinato) phosphazene] (PPHOS-100), were surgically implanted into a metaphyseal rabbit defect of the distal femur as constructs for tissue regeneration. Poly(lactide-co-glycolide) (PLAGA) implants, which are the biodegradable polymers most widely used clinically, and defects without polymers were used as controls in this experiment. Histological studies demonstrated that both PPHOS-50 and PPHOS-100 appeared to support bone growth comparable to the control PLAGA. By 12 weeks, femurs with polyphosphazene implants showed evidence of bone in-growth and a mild fibrous response. The PPHOS-50 implants were found to have a local tissue response that was more favorable than PPHOS-100 and similar to PLAGA. Biodegradable polyphosphazenes are a novel class of polymers which have been observed to facilitate bone growth in vivo.     

Polyurethane/poly[bis(carboxylatophenoxy)phosphazene] blends and their potential as flame‐retardant materials

A functionalized polyphosphazene, poly[bis(carboxylatophenoxy)‐phosphazene], was blended with a structural polyurethane via reactive mixing of the polymer with diisocyante and diol prepolymers. The thermal stabilites of the resultant foams were analyzed by thermogravimetric analysis (TGA). The char yields at both 400°C and 600°C increased relative to the pure polyurethane upon increasing the amount of polyphosphazene from 5 wt% to 20 wt%. At higher incorporations, the char at 400°C remained the same, but the char at 600°C continued to increase. The combustion behavior of these foams was analyzed both qualitatively, by a horizontal flame test, and quantitatively, by oxygen index (OI) measurements. Both of these tests indicated an increase in flame resistance at loadings of 20 wt% and above.     

Fluorinated polyphosphazene polyelectrolytes

Polyphosphazene polyelectrolytes containing various amounts of hydrophobic fluorinated moieties and ionic carboxylic acid groups were synthesized. Polymer compositions and molecular weights were characterized by NMR and gel permeation chromatography. Interestingly, poly[(carboxylatophenoxy)(trifluoroethoxy)phosphazene] containing 60 mol % fluorinated groups was found to be soluble in aqueous solutions. The behavior of fluorinated polyelectrolytes in reactions of ionic complexation with multivalent and monovalent salts was studied in aqueous solutions and ethanol–water mixtures. Such reactions led to the formation of ionotropic hydrogels under mild conditions and, thus, are of importance to the development of microencapsulation processes and controlled release formulations. All of the synthesized polymers underwent phase separation in the presence of multivalent ionic crosslinkers, such as spermine and calcium chloride. This included a water‐soluble polyelectrolyte containing 40 mol % ionic groups and hydrophobic polymer with only 3 mol % carboxylic acid groups. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 53–58, 2007     

Photochemical behavior of poly(organophosphazenes). XI. Photochemistry of poly[bis(4-benzylphenoxy) phosphazene]

In this paper we present results on the photolysis of poly[bis(4-benzylphenoxy)-phosphazene] in solution and in film, both in the presence and in the absence of molecular oxygen. Light irradiation of the polymer in oxygen-saturated CH₂Cl₂ solutions results in a remarkable degradation of the polyphosphazene, while in argon-purged solutions no appreciable variations of the polymer structure could be detected. The photolysis of poly[bis(4-benzylphenoxy)phosphazene] in films induces the cross-linking of the polymer regardless of the presence or the absence of molecular oxygen. The main process observed during the photochemistry both in solution and in the solid state of the polymer is the oxidation of the 4-benzylphenoxy group on the polyphosphazene, without involvement of the inorganic -P=N- backbone. The effect of temperature on the photolysis of the polyphosphazene substrate in film is also reported.     

In vitro degradation and release profiles of poly‐DL‐lactide‐poly(ethylene glycol) microspheres with entrapped proteins

Poly‐DL ‐lactide (PLA) and poly‐DL ‐lactide‐poly(ethylene glycol) (PELA) were produced by bulk ring‐opening polymerization using stannous chloride as initiator. PLA, PELA microspheres, and PELA microspheres containing the outer membrane protein (OMP) of Leptospira interrogans with the size of 1.5–2 μm were prepared by a solvent evaporation process. In vitro degradation and release tests of PLA, PELA, and OMP‐loaded PELA microspheres were performed in pH 7.4 buffer solution at 37°C. Quantitatively, the degree of degradation was monitored by detecting the molecular weight reduction, by evaluating the mass loss and the apparent degradation rate constant, and by determining the intrinsic viscosity and poly(ethylene glycol) content of retrieved polymer, while the release profile was assessed by measuring the amount of protein presented in the release medium at various intervals. Qualitatively, the morphological changes of microspheres were observed with scanning electron micrography. The observed relative rates of mass loss versus molecular weight reduction are consistent with a bulk erosion process rather than surface erosion for PELA microspheres. The introduction of hydrophilic poly(ethylene glycol) domains in copolymer PELA and the presence of OMP within microspheres show critical influences on the degradation profile. The OMP‐loaded PELA microspheres present triphasic release profile and a close correlation is observed between the polymer degradation and the OMP release profiles. It is suggested that the polymer degradation rate, protein diffusion coefficient, and the water‐swollen structure of microspheres matrix commonly contribute to the OMP release from PELA microspheres. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 140–148, 2000     

Grafting reactions onto polyorganophosphazenes. V. Photostabilization of poly[bis(4-benzylphenoxy)-phosphazene] by light-induced grafting copolymerization of acrylate polymers containing pendant HALS moieties

The light-induced grafting reaction of acrylate monomers containing hindered piperidine groups (HALS) onto poly[bis(4-benzylphenoxy)phosphazene] is described as a function of several different experimental parameters, i.e., type of photoinitiator (benzophenone or benzoin ethyl ether), monomer concentration, solvent composition, light intensity, and swelling of the polyphosphazene films. The obtained phosphazene-g-HALS-containing acrylate-grafted copolymers, irradiated with light of wavelength longer than 300 nm under accelerated photooxidative conditions to test the photostabilizing ability of the grafted HALS groups, showed that the hindered piperidine groups grafted onto the polyphosphazene matrix are able to considerably depress the damage caused to the poly[bis(4-benzylphenoxy)phosphazene] films during light exposure. The efficiency of this process seems to be related to the amount of HALS residues grafted onto the phosphazene substrates. © 1996 John Wiley & Sons, Inc.     

Polyphosphazene membranes. III. Solid‐state characterization and properties of sulfonated poly[bis(3‐methylphenoxy)phosphazene]

Poly[bis(3‐methylphenoxy)phosphazene] was sulfonated in a solution with SO₃ and solution‐cast into 100–200‐μm‐thick membranes from N,N‐dimethylacetamide. The degree of polymer sulfonation was easily controlled and water‐insoluble membranes were fabricated with an ion‐exchange capacity (IEC) as high as 2.1 mmol/g. For water‐insoluble polymers, there was no evidence of polyphosphazene degradation during sulfonation. The glass transition temperature varied from −28°C for the base polymer to −10°C for a sulfonated polymer with an IEC of 2.1 mmol/g. The equilibrium water swelling of membranes at 25°C increased from near zero for a 0.04‐mmol/g IEC membrane to 900 % when the IEC was 2.1 mmol/g. When the IEC was < 1.0 mmol/g, SO₃ attacked the methylphenoxy side chains at the para position, whereas sulfonation occurred at all available aromatic carbons for higher ion‐exchange capacities. Differential scanning calorimetry, wide‐angle X‐ray diffraction, and polarized microscopy showed that the base polymer, poly[bis(3‐methylphenoxy)phosphazene], was semicrystalline. For sulfonated polymers with a measurable IEC, the 3‐dimensional crystal structure vanished but a 2‐dimensional ordered phase was retained. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 387–399, 1999     

Synthesis,Characterization, Hydrolytic Degradation,and Biocompatibility of Poly[bis(lactic acid ester)phosphazenes)]

New biodegradable polyphosphazenes containing lactic acid ester side groups were synthesized via a route of macromolecular substitution. Their biodegradability and biocompatibility were studied in vitro. The polymers showed the fastest hydrolysis in the basic solution, followed by the acidic and then the neutral solution. The rate of these polymers' degradation decreased in the order of poly[bis(ethyl lactato)phosphazene] > poly[bis(propyl lactato)phosphazene] > poly[bis(butyl lactato)phosphazene]. The possible degradation pathways were discussed. MTT assays indicated that these polymers had good biocompatibility against HepG2 and K562/VCR cells. Due to good biodegradability and biocompatibility, these polyphosphazenes may be promising for biomedical applications.     

Grafting reactions onto poly(organophosphazenes). VI. Thermooxidative stabilization of poly[bis (4-benzylphenoxy)phosphazene] by grafting acrylate polymers containing HALS groups

Poly[bist 4-benzylphenoxy phosphazene] is heated at 200 C in air and the oxidation of the 4-diphenylmethane side substituent to phosphazene-supported benzophenone, benzhydrol, and hydroperoxides is observed. The thermo-oxidative stabilization of the polymer is obtained by light-induced grafting copolymerization of the acrylic acid 2.2.6.6-tetramethyl-piperidin-4-yl ester onto the polyphosphazene substrate. The HALS moieties grafted onto the polyphosphazene films prevent the oxidative modification of the substituents and preserve the polymer against thermal damage. This process, investigated by IR. UV, and EPR spectroscopy, is basically dependent on the amount of HALS groups grafted onto the polyphosphazene matrix and on the composition of the reaction medium used to carry out the grafting process. The comparison between the thermooxidative stabilization process and the corresponding photooxidative stabilization reaction is also discussed.Presented at the 1st Italian Workshop on Cyclo- and Poly(phosphazene) Materials. Lebruary 15–16, 1996, at the CNR Research Area in Padova, Italy.     

Synthesis and characterization of pH-sensitive and biodegradable hydrogels prepared by γ irradiation using microbial poly(γ-glutamic acid) and poly(ϵ-lysine)

Poly(γ-glutamic acid) (PGA) and poly(?-lysine) (PL) solutions were used as components to prepare mixed hydrogels by γ irradiation. A PGA and PL mixed solution was crosslinked to form a hydrogel with specific water content (weight of absorbed water/weight of dry gel) of 10–100 when the 5 wt % solution of mixed polymer was exposed to γ radiation of 87 kGy dosage under N₂ atmosphere. The specific water content increased with increasing PGA content of the PGA/PL mixed gel. The influence of pH and salt concentration on equilibrium swelling was studied. A characteristic pH-sensitive swelling behavior was obtained using compositional changes of PGA and PL in the gel. PGA/PL 50/50 wt % mixed gel swelling in acid (pH < 4.0) and alkaline (pH > 6.0) conditions and was deswelled between pH 4.0 and 6.0 due to the ionic composition changes of the gel network. With an increase in the ratio of PGA to PL, the hydrogels showed increasing sensitivity to salt solutions (NaCl, Na₂SO₄, and CaCl₂). In addition, degradation of PGA/PL gel by protease produced from Aspergillus oryzae was investigated at 40°C and pH 7.0. PL gel was degraded completely within 2 days. An increase in the ratio of PAG in the PGA/PL mixed gel led to a decrease in the degree of degradation as expected. Some subtle degradation changes were found in the 50/50 and 80/20 wt % (PGA/PL) gels that were degraded by only 3.5 and 3.8% by protease, respectively. © 1995 John Wiley & Sons, Inc.     

Polyphosphazene membranes. IV. Polymer morphology and proton conductivity in sulfonated poly[bis(3‐methylphenoxy)phosphazene] films

The microstructure of sulfonated poly[bis(3‐methylphenoxy)phosphazene] was studied using wide‐ and small‐angle X‐ray diffraction. A reflection peak, attributed to the presence of ionic clusters, was observed in the small‐angle X‐ray diffraction patterns of hydrated and dry polymers with an ion‐exchange capacity (IEC) ≥0.6 mmol/g. The Bragg spacing from the ionic cluster structure was about 30 Å for the nonhydrated polymer and 50 to 90 Å for fully hydrated films. The effects of IEC, cation form of the polymer, temperature, and polymer water content on the cluster structure were investigated. The specific proton conductivity of water‐swollen, sulfonated poly[bis(3‐methylphenoxy)phosphazene] films at 25°C increased with increasing IEC, with a maximum conductivity of 0.1 S/cm at a polymer ion‐exchange capacity of 1.6 mmol/g. The water‐content percolation threshold for conductivity was between 17.5 and 25 vol %, and decreased with polymer IEC. The temperature dependence of proton conductivity for 1.2 mmol/g IEC poly[bis(3‐methylphenoxy)phosphazene] membranes exhibited Arrhenius behavior with an apparent activation energy of 27.8 and 36.7 kJ/mol for crosslinked and noncrosslinked polymers, respectively. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 79: 49–59, 2001     

Continuous distribution kinetics for ultrasonic degradation of poly(methyl methacrylate)

Ultrasonic degradation of poly(methyl methacrylate) (PMMA) was carried out in several solvents and some mixtures of solvents. The time evolution of molecular weight distribution (MWD), determined by gel permeation chromatography, is analysed by continuous distribution kinetics. The rate coefficients for polymer degradation are determined for each solvent. The variation of rate coefficients is correlated with the vapour pressure of the solvent, kinematic viscosity of the solution and solvent–polymer interaction parameters. The vapour pressure and the kinematic viscosity of the solution are found to be more critical than other parameters (such as the Huggins and Flory–Huggins constants) in determining the degradation rates. © 2001 Society of Chemical Industry     

Photochemical Behavior of Poly(Organophosphazenes). 15. Light-Induced Cross-Linking of [(4-Benzoylphenoxy)x(Methoxyethoxyethoxy)2 ? x] Phosphazene Copolymers

The synthesis of a new, highly photosensitive, phosphazene copolymer containing an almost-equimolecular quantity of benzophenone and methoxyethoxyethoxy substituents is reported in this paper, together with the photochemical behavior of this material when irradiated in film both in oxygen and in an argon atmosphere. It has been detected that the photoreactivity of the phosphazene material strongly depends on the light absorption process by the benzophenone moieties, whose selective excitation predominantly brings about an intramolecular hydrogen abstraction reaction from the ethylene oxide units, thus producing highly reactive phosphazene macroradicals. The coupling reactions of these species results in the complete cross-linking of the polyphosphazene substrate and in its total insolubilization. Moreover, the influence of molecular oxygen on the overall photochemical process of the benzophenone/ethyleneoxide-substituted phosphazene copolymer is investigated. The implications of the light-induced reticulation process in the controlled insolubilization of poly[ bis (methoxyethoxyethoxy)phosphazene] are also discussed.     

Photochemical Behavior of Poly(Organophosphazenes). 15. Light-Induced Cross-Linking of [(4-Benzoylphenoxy) x (Methoxyethoxyethoxy)2 − x ] Phosphazene Copolymers

The synthesis of a new, highly photosensitive, phosphazene copolymer containing an almost-equimolecular quantity of benzophenone and methoxyethoxyethoxy substituents is reported in this paper, together with the photochemical behavior of this material when irradiated in film both in oxygen and in an argon atmosphere. It has been detected that the photoreactivity of the phosphazene material strongly depends on the light absorption process by the benzophenone moieties, whose selective excitation predominantly brings about an intramolecular hydrogen abstraction reaction from the ethylene oxide units, thus producing highly reactive phosphazene macroradicals. The coupling reactions of these species results in the complete cross-linking of the polyphosphazene substrate and in its total insolubilization. Moreover, the influence of molecular oxygen on the overall photochemical process of the benzophenone/ethyleneoxide-substituted phosphazene copolymer is investigated. The implications of the light-induced reticulation process in the controlled insolubilization of poly[ bis (methoxyethoxyethoxy)phosphazene] are also discussed.     

Characteristics of zwitterionic sulfobetaine acrylamide polymer and the hydrogels prepared by free-radical polymerization and effects of physical and chemical crosslinks on the UCST

A zwitterionic sulfobetaine polymer, poly(N,N-dimethyl(acrylamidopropyl) ammonium propane sulfonate) (poly(DMAAPS)), and the hydrogels of this polymer were synthesized by free-radical polymerization in an aqueous redox system using a wide range of monomer concentrations (C_m). The resulting polymers were characterized in terms of polymer yield, intrinsic viscosity, molecular weight, gel fraction, and thermoresponsive phase-transition behavior. Parameters in the Mark–Houwink–Sakurada equation, including the molecular-weight exponent α, were determined for poly(DMAAPS) in 0.1 M NaCl aqueous solution. The physical state and transparency of the poly(DMAAPS) samples were strongly dependent on C_m and temperature. At higher values of C_m (i.e. above a critical molecular weight), poly(DMAAPS) became a gel comprising a physically crosslinked network consisting of entangled polymer chains and interchain associations of the zwitterionic groups. The poly(DMAAPS) solutions or gels exhibited a thermoresponsive phase transition with an upper critical solution temperature (UCST). The gels obtained were completely soluble in aqueous NaCl solution at ambient temperature as well as in water at temperatures above UCST. The effects of molecular weight, chemical crosslink density and copolymerization on the UCST were also elucidated.     

Synthesis and characterization of nanosized poly(organophosphazenes) with methoxy-poly(ethylene glycol) and dipeptide ethyl esters as side groups

Nanosized water soluble poly(organophosphazenes) were synthesized by grafting hydrophilic methoxy poly(ethylene glycols) and hydrophobic dipeptide ethyl esters as side groups to the phosphazene backbone. Their hydrodynamic volume could be controlled in the range of 10-30 nm in diameter depending on the length of the side groups and the molecular weight of the polymers. These polymers exhibited a lower critical solution temperature in the range of 60-105 °C and hydrolytic degradability, which can afford applications to a variety of drug delivery systems. The hydrolytic properties of the present poly(organophosphazenes) have been studied at 37 °C in different pH buffer solutions by means of gel permeation chromatography. The polymers substituted with the more hydrophobic and more bulky dipeptide groups caused slower hydrolysis and the polymer hydrolysis occurred more rapidly in the acidic buffer solution than in the neutral and basic solutions.