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PubMed2005

Molecular depth profiling of multilayer polymer films using time-of-flight secondary ion mass spectrometry.

The low penetration depth and high sputter rates obtained using polyatomic primary ions have facilitated their use for the molecular depth profiling of some spin-cast polymer films by secondary ion mass spectrometry (SIMS). In this study, dual-beam time-of-flight (TOF) SIMS (sputter ion, 5 keV SF(5)(+); analysis ion, 10 keV Ar(+)) was used to depth profile spin-cast multilayers of poly(methyl methacrylate) (PMMA), poly(2-hydroxyethyl methacrylate) (PHEMA), and trifluoroacetic anhydride-derivatized poly(2-hydroxyethyl methacrylate) (TFAA-PHEMA) on silicon substrates. Characteristic positive and negative secondary ions were monitored as a function of depth using SF(5)(+) primary ion doses necessary to sputter through the polymer layer and uncover the silicon substrate (>5 x10(14) ions/cm(2)). The sputter rates of the polymers in the multilayers were typically less than for corresponding single-layer films, and the order of the polymers in the multilayer affected the sputter rates of the polymers. Multilayer samples with PHEMA as the outermost layer resulted in lowered sputter rates for the underlying polymer layer due to increased ion-induced damage accumulation rates in PHEMA. Additionally, the presence of a PMMA or PHEMA overlayer significantly decreased the sputter rate of TFAA-PHEMA underlayers due to ion-induced damage accumulation in the overlayer. Typical interface widths between adjacent polymer layers were 10-15 nm for bilayer films and increased with depth to approximately 35 nm for the trilayer films. The increase in interface width and observations using optical microscopy showed the formation of sputter-induced surface roughness during the depth profiles of the trilayer polymer films. This study shows that polyatomic primary ions can be used for the molecular depth profiling of some multilayer polymer films and presents new opportunities for the analysis of thin organic films using TOF-SIMS.

Acetic Anhydrides↗

PubMed1979

Selective repression of transcription by base sequence specific synthetic polymers.

We report the effect of novel synthetic polymers on deoxyribonucleic acid (DNA) directed ribonucleic acid (RNA) synthesis in vitro. Polymers contained base-selective monomers, including a GC-specific phenazine derivative and an AT-specific triphenylmethane dye. Radical chain polymerization was carried out in aqueous solution by using monomers bound to a template DNA, which was obtained from either lambda or T7 bacteriophage. Polymers were isolated and reannealed with DNA samples, including competitive mixtures of T7 and lambda DNAs. We measured transcription from DNA-polymer complexes by using Escherichia coli RNA polymerase and determined not only the reduction in total transcription levels but also the relative inhibition of lambda- or T7-specific transcription by using a hybridization assay. The results show that micromolar concentrations of individual dyes are sufficient to cause substantial inhibition of transcription when the dyes are incorporated into polymers. More significantly, a number of the polymers inhibited more strongly transcription from the DNA which had served as template for polymer synthesis than from the DNA present as competitor in the annealing process. We conclude that template synthesis of DNA-binding polymers can lead to preferential inhibition of function of the original template. The apparent relative affinity of polymer for competing DNAs can be altered by at least an order of magnitude depending on which DNA was used as the synthesis template. The results offer a new approach to improving the specificity of DNA-binding drugs.

Coloring Agents↗

PubMed2001

Biocompatible polyester macroligands: new subunits for the assembly of star-shaped polymers with luminescent and cleavable metal cores.

The synthesis of a series of star-shaped, biocompatible polyesters--polylactides (PLAs), polycaprolactones (PCLs), and various copolymer analogues--with either labile iron(II) tris-bipyridyl or luminescent ruthenium(II) tris-bipyridyl cores is described. These polymers were readily assembled by a convergent, metal-template-assisted approach that entailed the synthesis of bipyridine (bpy) ligands incorporating PLA- and PCL-containing arms and subsequent chelation of the "macroligands" to iron(II) or ruthenium(II). Specifically, the polyester macroligands bpyPLA(2) and bpyPCL(2) were prepared by a stannous octoate catalyzed ring-opening polymerization of DL- or L-lactide and epsilon-caprolactone, using bis(hydroxymethyl)-2,2'-bipyridine as the initiator. Copolymers bpy(PCL-PLA)(2) and bpy(PLA-PCL)(2) were generated in an analogous manner using bpyPLA(2) and bpyPCL(2) as macroinitiators. Polymers with narrow molecular weight distributions and with molecular weights close to values expected based upon monomer/initiator loading were produced. The macroligands were subsequently chelated to iron(II) to afford six-armed, iron-core star polymers, which were characterized by UV-vis and (1)H NMR spectroscopy. Estimated chelation efficiencies for formation of the star polymers (M(n) calcd: 20-240 kDa) were high, as determined by UV-vis spectral analysis. Within the molecular weight range investigated, differential scanning calorimetry and thermogravimetric analysis revealed that the small amounts of metal in the polyester stars and differences in polymer architecture had little effect on the thermal properties of the PLA/PCL materials. However, thin films of the red-violet colored iron-core stars exhibited reversible, thermochromic bleaching. Solutions and films of the polymers also responded (with color loss) to a variety of chemical stimuli (e.g., acid, base, peroxides, ammonia), thus revealing potential for use in diverse sensing applications. Likewise, the polyester macroligands were chelated to ruthenium(II) to produce both linear and star-shaped polymers, which were characterized by UV-vis and (1)H NMR spectral analysis. Molecular weights of the polymers were determined by gel permeation chromatography (M(n)(MALLS): 6-30 kDa) with in-line, UV-vis diode-array detection, confirming the presence of the [Ru(bpy)(3)](2+) core in the eluting polymer fractions. As was the case with the corresponding iron-core polyesters, estimated chelation efficiencies were high.

Biocompatible Materials↗

PubMedDate not supplied

The polymer-supported phospholipid bilayer: tethering as a new approach to substrate-membrane stabilization.

We present a new molecular engineering approach in which a polymer-supported phospholipid bilayer is vertically stabilized by controlled covalent tethering at both the polymer-substrate and polymer-bilayer interfaces. This approach is based on lipopolymer molecules, which not only form a polymer cushion between the phospholipid bilayer and a solid glass substrate but also act as covalent connections (tethers) between the bilayer and cushion. Our approach involves Langmuir-Blodgett transfer of a phospholipid-lipopolymer monolayer followed by Schaefer transfer of a pure phospholipid monolayer and is capable of varying the tethering density between the polymer layer and the phospholipid bilayer in a very controlled manner. Further stabilization is achieved if the glass substrate is surface-functionalized with a benzophenone silane. In this case, a photocross-linking reaction between the polymer and benzophenone group allows for the covalent attachment of the polymer cushion to the glass substrate. This approach is similar to that recently reported by Wagner and Tamm in which double tethering is achieved via lipopolymer silanes (Wagner, M. L.; Tamm, L. K. Biophys. J. 2000, 79, 1400). To obtain a deeper understanding of how the covalent tethering affects the lateral mobility of the bilayer, we performed fluorescence recovery after photobleaching (FRAP) experiments on polymer-tethered bilayers at different tethering densities (lipopolymer/phospholipid molar ratios). The FRAP data clearly indicate that the hydrophobic lipopolymer moieties act as rather immobile obstacles within the phospholipid bilayer, thereby leading to hindered diffusion of phospholipids. Whereas the high lateral diffusion coefficient of D = 17.7 mum(2)/s measured at low tethering density (5 mol % lipopolymer) indicates rather unrestricted motion within the bilayer, corresponding values at moderate (10 mol % lipopolymer) and high (30 mol % lipopolymer) tethering densities of D = 9.7 mum(2)/s and D = 1.1 mum(2)/s, respectively, show significant hindered diffusion. These results are contrary to the recent findings on similar membrane systems reported by Wagner and Tamm in which no significant change in phospholipid diffusion was found between 0 and 10 mol % lipopolymer. Our experimental report leads to a deeper understanding of the complex problem of interlayer coupling and offers a path toward a compromise between stability of the whole system and lateral mobility within the bilayer. Furthermore, the FRAP measurements show that polymer-tethered membranes are very interesting model systems for studying problems of restricted diffusion within two-dimensional fluids.

Diffusion↗

PubMedDate not supplied

Self-organization of amphiphilic polymer in vesicle bilayers composed of surfactant mixtures.

Cryogenic transmission electron microscopy (cryo-TEM) and small angle neutron scattering (SANS) are used to investigate the association of amphiphilic polymers consisting of a double-chain hydrophobic tail attached onto poly(ethylene glycol) (PEG) polymer chains into two different systems of equilibrium vesicles. For cetyltrimethylammonium bromide (CTAB)/sodium perfluorohexanoate (FC(5)) vesicle bilayers, the size distribution of the vesicles slightly becomes narrow in the presence of the polymers, suggesting that the wedge-shaped polymers increase the spontaneous curvature of the vesicles. In contrast, the confinement of polymer molecules inside the CTAB/sodium perfluorooctanoate (FC(7)) vesicles that are stabilized by spontaneous curvature causes an abrupt decrease in the bilayer rigidity. By an analysis of vesicle size distribution, it is found that the membrane elasticity of CTAB/FC(7) vesicles is varied considerably from 6k(B)T to 0.3k(B)T, implying the transition of stabilization mechanism from spontaneous curvature to thermal fluctuation in the presence of polymer. The polymer incorporation mechanism into the bilayers is understood, in the comparison of the vesicle radius and size distribution before and after adding polymer, as that the polymer is anchored into the vesicle bilayer owing to hydrophobic property after the adsorption on the surface of the bilayer.

Caproates↗

PubMedDate not supplied

Understanding the mechanism of action of poly(amidoamine)s as endosomolytic polymers: correlation of physicochemical and biological properties.

Bioresponsive poly(amidoamine)s (PAA)s are currently under development as endosomolytic polymers for intracellular delivery of proteins and genes. Here for the first time, small-angle neutron scattering (SANS) is used to systematically investigate the pH-dependent conformational change of an endosomolytic polymer, the PAA ISA 23. The radius of gyration of the ISA23 was determined as a function of pH and counterion, the aim being to correlate changes in polymer conformation with membrane activity assessed using a rat red blood cell haemolysis assay. With decreasing pH, the ISA23 radius of gyration increased to a maximum (R(g) approximately 80 A) around pH = 3, before subsequently decreasing once more. At high pH and therefore high ionic strengths, the polymer is negatively charged and adopts a rather compact structure (R(g) approximately 20 A), presumably with the dissociated carboxylic groups on the exterior of the polymer coil. At low pH, the coil again collapses (R(g) < 20 A), presumably due to the effects of the high ionic strength. It is concluded that the nature of the salt form has no direct bearing on the size of the polymer coil, but it does indirectly determine the prevailing pH and, hence, polymer conformation. Pulsed-gradient spin-echo NMR measurements were in good agreement with the SANS estimates of the radius of gyration, although ISA23 polydispersity does complicate the data interpretation/comparison. These results support the proposed mode of action of PAAs, namely a coil expansion on passing from a neutral pH (extracellular) to an acidic pH (endosomal and lysosomal) environments. The results do, however, suggest that the charge on the polymer shows a closer correlation with the haemolysis activity rather than the polymer conformation.

Animals↗

PubMedDate not supplied

Microscopy of DNA in dilute polymer solutions.

The mechanism of separation of DNA in polymer solutions is not well understood. In this paper we use epifluorescence videomicroscopy to investigate the dynamic behavior of DNA electrophoresing through dilute polymer solutions. DNA collides with polymer obstacles, which cause the conformation of DNA to change from the globular, random coil conformation it takes in free solution. There are two main types of DNA-polymer collisions: U-shape collisions and brief collisions. In U-shape collisions, the DNA collides with a polymer obstacle, extends into a U-shape, and then slides around the polymer obstacle like a pulley. There are occasionally multiple entanglement points, causing the DNA to take more complex conformations, such as W-shapes. In the brief collision process, the DNA collides with a polymer obstacle and begins to extend but then collapses back into its globular conformation before a full U-shape is formed. The frequency of these interactions increases as the DNA size increases, and it also increases when the polymer size or concentration increases. These data support the transient entanglement coupling mechanism of separation of DNA, which states that entanglements between DNA and polymer molecules result in the separation of DNA.

Biotechnology↗

PubMed2005

Copper-glyphosate sorption to microcrystalline gibbsite in the presence of soluble Keggin Al13 polymers.

Among the most reactive yet largely neglected adsorbents of toxicant species occurring in acidic aquatic environments are the epsilon-Keggin Al13 polyoxocations [AlO4Al12(OH)24(H2O)12(7+)], known generally as Al13 polymers. Here, we report on the sorption of Cu(II), a common ingredient of pesticides, and glyphosate {N-[phosphonomethyl]glycine (PMG)}, a widely applied herbicide, to microcrystalline gibbsite [gamma-Al(OH)3] in the presence of soluble Al13 polymers over the pH range 4-7. In the presence of gibbsite and soluble Al13 polymers, dissolved Cu(II) decreased gradually with pH, achieving a minimum at pH 5.5. Between pH 5.5 and 6.0, however, soluble Cu increased markedly, with approximately 80% of the added metal remaining in solution at pH 5.86. At pH > 6.0, soluble Cu once again decreased, becoming undetectable at pH 7. The anomalous Cu solubilization was attributed to a concomitant deprotonation of soluble Al13 polymers, yielding surface OH groups possessing high affinity for Cu(II). Removal of Cu from solution at pH > 6.0 is facilitated by flocculation of the Al13 polymers to which Cu had sorbed. The sorption behavior of the zwitterionic PMG in the presence of gibbsite and Al13 polymers was consistent with this interpretation, there being a dramatic increase in sorbed PMG at pH > 6.0 as the Al13 polymers deprotonated and flocculated. Copper and PMG loss from solution with increasing pH when both adsorptives were added to the gibbsite-Al13 polymer system was broadly similar to what was observed in the PMG-free systems, although small differences were detected in response to varying the order of adsorptive addition. The inclusion of soluble Al polymers in our experiments exposes a fundamental limitation of models based on but a single inorganic adsorbent as a means to predict the behavior of trace metals and xenobiotic organic compounds in natural systems.

Adsorption↗

PubMed1995

Effective inhibitors of hemagglutination by influenza virus synthesized from polymers having active ester groups. Insight into mechanism of inhibition.

Highly effective sialic acid-containing inhibitors of influenza virus X-31 were synthesized using poly[N-(acryoyloxy)succinimide] (pNAS), a polymer preactivated by incorporation of active ester groups. Polymers containing two and three different components were prepared by sequential reaction of pNAS with two and three amines, respectively. This preparation of co- and terpolymers was synthetically more efficient than methods involving copolymerization of different monomers and gave polymers that were more easily compared than those generated by copolymerization. Polymers in this study (prepared from a single batch of pNAS) had a constant degree of polymerization (DP approximately 2000) and probably had a distribution of components that was more random than analogous polymers prepared by copolymerization. Use of C-glycosides of sialic acid made it possible to investigate inhibition by different polymers at temperatures ranging from 4 to 36 degrees C without artifacts due to the hydrolytic action of neuraminidase. The inhibitors were, in general, more effective at 36 degrees C than at 4 degrees C. The hemagglutination (HAI) assay was used to measure the value of the inhibition constant KHAIi each polymer. The value of KHAIi for the two-component polymer containing 20% sialic acid on a polyacrylamide backbone at 4 degrees C was 4 nM (in terms of the sialic acid moieties present in solution) and was approximately 50-fold more effective than the best inhibitors previously described and 25-fold more effective than the best naturally occurring inhibitor. The most effective inhibitor synthesized in this work contained 10% benzyl amine and 20% sialic acid on a polyacrylamide backbone, and its value of KHAIi was 600 pM at 36 degrees C. Approximately 100 polymers that differed in one or two components were assayed to distinguish between two limiting mechanisms for inhibition of the interaction between the surfaces of virus and erythrocytes: high-affinity binding through polyvalency, and steric stabilization. The results suggest that both mechanisms play an important role. The system comprising polyvalent inhibitors of agglutination of erythrocytes by influenza provides a system that may be useful as a model for inhibitors of other pathogen-host interactions, a large number of which are themselves polyvalent.

Animals↗

PubMed2006

Polymer modifies the critical region of the coexisting liquid phases.

Several recent conceptual advances, which take advantage of the polymer conformation in the near critical point of coexisting liquid phases and practical techniques of some unique molecular interactions between polymer chain and the solvent molecules, have been made to allow the investigation of the effect of the well-defined polymer in phase separation of binary mixtures. The behavior of a flexible linear or branched chain polymer (polyethylene oxide, PEO, MW = 9 x 10(5), as an impurity) in the critical binary mixture of isobutyric acid (I) + water (W) was studied by the refractive index (n) measurements using a very accurate and sensitive refractometer. The refractive index in each phase of IW as well as three different PEO concentrations (C = 0.395, 0.796, and 1.605 mg/cm(3)) in the near critical composition of IW have been measured at temperatures below the system's upper critical point. We observed that the polymer was significantly affected in the critical region of IW and these various concentrations of PEO show an important behavior on the critical exponents (beta), the critical temperatures (T(c)), and critical composition (phi(c)), which are depicting the shape of the coexistence curve. The phase-transition region of coexisting phases of IW shifts down with the addition of PEO and T(c) decreases linearly with increasing PEO concentrations. This may indicate that the polymer chain entangles with each phase, thereby the polymer monomers strongly interact with neighbor solvent particles and also intrachain interaction between the polymer segments. At such conditions, the collapse of polymer chain is possible in the vicinity of the critical point. At temperatures T close enough to T(c), the critical exponent beta (defined by the relation (n(1) - n(2)) proportional, variant (T(c) - T)(beta), with n(1) and n(2) being the refractive indices of the coexisting phases) was found to decrease from 0.382 to 0.360 when the PEO concentration changes from 0.395 to 1.605 mg/cm(3). These values are higher than that of 0.326 +/- 0.005 of pure IW, which is compatible with the three-dimensional Ising value beta = 0.325. The observed critical exponents for the PEO in IW are fully renormalized Ising critical exponents. Besides, the phi(c) values decrease with increasing the C values in the mixture of IW. It appears that the shape of the PEO in IW coexistence curves is similar from that of pure IW.

Chemistry, Physical↗

PubMedDate not supplied

Blocking nitrosamine formation with polymers.

A set of polymers have been synthesized in order to determine whether polymers containing nitrosation-reactive functional groups could effectively block nitrosamine formation. Polymers containing both hydrophobic backbones [poly[(chloromethyl)styrene], poly(ethylene oxide-co-epichlorohydrin), chloromethylated cross-linked polystyrene] and hydrophilic backbones [poly(ethylenimine) and poly(acryloyl chloride)] have been derivatized with pyrrole, 2,5-dimethylpyrrole, 2-[(methylamino)methyl]pyrrole, or hydroquinone. All of these polymers, as well as PEI itself, are effective at blocking the nitrosation of morpholine by nitrous acid. The hydrophilic polymers are much better able to compete for the available nitrosating agent in aqueous solution than are the hydrophobic polymers. Nevertheless, all of the polymers were highly effective in scavenging nitrous acid from aqueous solution prior to addition of the amine. The reaction products derived from the reactive, polymer-attached functional groups are retained on the polymer and are easily removed from mixtures of chemicals by physical means. Since nitrosamines and other N-nitroso compounds are known to be potent animal carcinogens, this work is of significance in the area of preventive chemical toxicology.

Binding, Competitive↗

PubMed2003

Electrostatic nanolithography in polymers using atomic force microscopy.

The past decade has witnessed an explosion of techniques used to pattern polymers on the nano (1-100 nm) and submicrometre (100-1,000 nm) scale, driven by the extensive versatility of polymers for diverse applications, such as molecular electronics, data storage, optoelectronics, displays, sacrificial templates and all forms of sensors. Conceptually, most of the patterning techniques, including microcontact printing (soft lithography), photolithography, electron-beam lithography, block-copolymer templating and dip-pen lithography, are based on the spatially selective removal or formation/deposition of polymer. Here, we demonstrate an alternative and novel lithography technique--electrostatic nanolithography using atomic force microscopy--that generates features by mass transport of polymer within an initially uniform, planar film without chemical crosslinking, substantial polymer degradation or ablation. The combination of localized softening of attolitres (10(2)-10(5) nm3) of polymer by Joule heating, extremely non-uniform electric field gradients to polarize and manipulate the soften polymer, and single-step process methodology using conventional atomic force microscopy (AFM) equipment, establishes a new paradigm for polymer nanolithography, allowing rapid (of the order of milliseconds) creation of raised (or depressed) features without external heating of a polymer film or AFM tip-film contact.

Microscopy, Atomic Force↗

PubMed2006

Hydrogen cyanide polymers, comets and the origin of life.

Hydrogen cyanide polymers--heterogeneous solids ranging in colour from yellow to orange to brown to black--could be major components of the dark matter observed on many bodies of the outer solar system including asteroids, moons, planets and, especially, comets. The presence on cometary nuclei of frozen volatiles such as methane, ammonia and water subjected to high energy sources makes them attractive sites for the ready formation and condensed-phase polymerization of hydrogen cyanide. This could account for the dark crust observed on Comet Halley in 1986 by the Vega and Giotto missions. Dust emanating from its nucleus would arise partly from HCN polymers as suggested by the Giotto detection of free hydrogen cyanide, CN radicals, solid particles consisting only of H, C and N, or only of H, C, N, O, and nitrogen-containing organic compounds. Further evidence for cometary HCN polymers could be expected from in situ analysis of the ejected material from Comet Tempel 1 after collision with the impactor probe from the two-stage Deep Impact mission on July 4, 2005. Even more revealing will be actual samples of dust collected from the coma of Comet Wild 2 by the Stardust mission, due to return to Earth in January 2006 for analyses which we have predicted will detect these polymers and related compounds. In situ results have already shown that nitriles and polymers of hydrogen cyanide are probable components of the cometary dust that struck the Cometary and Interstellar Dust Analyzer of the Stardust spacecraft as it approached Comet Wild 2 on January 2, 2004. Preliminary evidence (January 2005) obtained by the Huygens probe of the ongoing Cassini-Huygens mission to Saturn and its satellites indicates the presence of nitrogen-containing organic compounds in the refractory organic cores of the aerosols that give rise to the orange haze high in the atmosphere of Titan, Saturn's largest moon. Our continuing investigations suggest that HCN polymers are basically of two types: ladder structures with conjugated -C=N- bonds and polyamidines readily converted by water to polypeptides. Thermochemolysis GC-MS studies show that cleavage products of the polymer include alpha-amino acids, nitrogen heterocycles such as purines and pyrimidines, and provide evidence for peptide linkages. Hydrogen cyanide polymers are a plausible link between cosmochemistry and the origin of informational macromolecules. Implications for prebiotic chemistry are profound. Following persistent bolide bombardment, primitive Earth may have been covered by water and carbonaceous compounds, particularly HCN polymers which would have supplied essential components for establishing protein/nucleic acid life.

Cosmic Dust↗

PubMed2001

Branched co-polymers of histidine and lysine are efficient carriers of plasmids.

We previously determined that a linear co-polymer of histidine and lysine (HK) in combination with liposomes enhanced the transfection efficiency of cationic liposomes. In the current study, we designed a series of HK polymers with increased branching and/or histidine/lysine ratio to determine if either variable affects transfection efficiency. In the presence of liposomes, the branched polymer with the highest number of histidines, HHK4b, was the most effective at enhancing gene expression. Furthermore, when serum was added to the medium during transfection, the combination of HHK4b and liposomes as a gene-delivery vehicle increased luciferase expression 400-fold compared to liposomes alone. In contrast to linear HK polymers, the higher branched HHK polymers were effective carriers of plasmids in the absence of liposomes. Without liposomes, the HHK4b carrier enhanced luciferase expression 15-fold in comparison with the lesser branched HHK2b carrier and increased expression by 5-logs in comparison with the HHK or HK carrier. The interplay of several parameters including increased condensation of DNA, buffering of acidic endosomes and differential binding affinities of polymer with DNA have a role in the enhancement of transfection by the HK polymers. In addition to suggesting that branched HK polymers are promising gene-delivery vehicles, this study provides a framework for the development of more efficient peptide-bond-based polymers of histidine and lysine.

Amino Acid Sequence↗

PubMed1996

Efficacy of intralesionally administered cisplatin-impregnated biodegradable polymer for the treatment of 9L gliosarcoma in the rat.

OBJECTIVE: Use of biodegradable polymers for the local delivery of chemotherapy is a promising new strategy in the treatment of high-grade gliomas. We examine the benefit of local delivery of cisplatin, via biodegradable polymer, in the treatment of intracranial glioma in rats. This treatment is compared against intralesionally administered free cisplatin and systemic cisplatin. METHODS: The Fischer 344 9L gliosarcoma rat model was used with a cannula placed in the right frontal lobe. On Day 0, 5 x 10(3) 9L gliosarcoma cells were infused. Treatment was initiated on Day 7. In Experiment 1, polymer alone was infused intralesionally to rule out any inherent toxic or tumoricidal properties. In Experiment 2, polymer impregnated with 0.5, 5.0, and 25 mg/m2 cisplatin was infused intralesionally. In Experiment 3, the most effective dose of drug containing polymer was compared against a similar dose of intralesionally administered free cisplatin and the systemic administration of cisplatin. RESULTS: In Experiment 1, polymer alone demonstrated no inherent toxic or tumoricidal properties. In Experiment 2, polymer impregnated with 0.5 mg/m2 was 100% effective in eradicating intracranial tumor with minimal histological evidence of toxicity. At the 5.0 and 25 mg/m2 doses, local brain toxicity was significant. In Experiment 3, at Day 60, 8 of 12 animals treated with polymer containing 0.5 mg/m2 cisplatin were alive and tumor free. This compared with 3 of 13 tumor-free survivors for the group treated with intralesionally administered free cisplatin, and 0 of 13 and 0 of 11 survivors for the 50 and 100 mg/m2 intraperitoneally administered doses, respectively. CONCLUSION: The local instillation of cisplatin-impregnated biodegradable polymer, allowing the sustained release of high-dose chemotherapy locally, seems to be effective treatment for intracranial 9L gliosarcoma in the rat. Treatment was superior to intralesionally administered free or systemic cisplatin.

Animals↗

PubMed1993

Cell transplantation of genetically altered cells on biodegradable polymer scaffolds in syngeneic rats.

Many severe metabolic deficiencies in children are caused by a single gene defect with a resultant single gene product deficiency. These diseases may be amenable to permanent cure using new techniques of gene transfer and cell transplantation. In many in vivo models of retroviral mediated gene therapy, a significant limiting factor is the ability to transplant a sufficient number of modified cells. To potentially circumvent this problem, we have developed a biodegradable polymer implant system capable of supporting large numbers of genetically modified cells. In this study, we inserted a reporter gene into syngeneic cultured normal fibroblasts and then transplanted these genetically modified cells into animals using synthetic biodegradable polymer fibers as temporary cell delivery scaffolds. To begin to develop a system capable of delivering desirable proteins secreted by genetically modified cells, Fischer 344 adult rat fibroblasts were transduced in tissue culture with a retrovirus containing the reporter gene Lac Z. These genetically modified cells (1.1 x 10(7) cells/graft) were then attached to the biodegradable polymer fibers and the polymer-cell graft was transplanted subdermally into syngeneic recipients (n = 9). There was persistence of the modified cells with expression of the reporter gene for at least 30 days. The estimated number of genetically modified cells per implanted graft decreased from a pretransplant value of 1.1 +/- 0.6 x 10(7) to 3.2 +/- 0.7 x 10(6) by 15 days after transplantation (P < 0.01). Thereafter, the cell number did not vary significantly to the conclusion of the study at day 30 (3.6 +/- 1.0 x 10(6) cells/graft). Evidence of ingrowth and incorporation of other stromal elements was present in the graft by 1 week post-transplantation, as judged by counterstained hematoxylin and eosin micrograph sections. Migration of modified cells to areas outside of the polymer-cell graft was not detected. Over the course of the study, there was little degradation of the polymer implant, although by day 30, evidence of early dissolution was evident. The number of polymer fibers per high power field increased slightly from 62.5 +/- 5.8 on day 1 to 77.3 +/- 26.6 on day 30 (P > 0.2). These data suggest that the use of biodegradable polymer fibers may permit the transplantation of genetically modified cells in sufficient numbers to deliver a therapeutically useful product. Polymer matrices allow for the attachment and site-specific transplantation of genetically modified cells.

Animals↗

PubMed2006

CO-alkene polymers are biocompatible scaffolds for primary urothelial cells in vitro and in vivo.

OBJECTIVE: To investigate CO-alkene polymers, novel synthetic nonbiodegradable polymers, as a potential biomaterial for urological applications. MATERIALS AND METHODS: Porcine urothelial cells were seeded on cover glasses (96 wells; 10 000 cells/well) coated with CO-alkene polymers [propylene/N-Acetyl-O'-(hex-5-enyl)-l-tyrosine ethyl ester/CO (PTCO) and hexene-CO (HxCO)]. The following conditions were investigated: cells seeded; (i) on PTCO, (ii) on HxCO, (iii) in PTCO-conditioned medium, (iv) in HxCO-conditioned medium, (v) on glass without polymers, (vi) on polystyrene, and (vii) on polystyrene treated with 1.25% NaCl (toxic control). Cell counts, cell death detection assay, and a cell activity assay (XTT, a tetrazolium-based colorimetric assay) were performed after 3, 6 and 9 days. Urothelial-cell seeded-PTCO films (0.5 x 10(6) cells/cm(2)) were implanted into the subcutaneous space of athymic mice for up to 12 weeks and unseeded PTCO polymers were implanted as a negative control. RESULTS: The urothelial cell adherence rates on the polymers were similar to those for glass and polystyrene. The cell activity (XTT assay) was higher in cells seeded on the polymers than in cells seeded on polystyrene and glass after 3 and 6 days. There were no significant differences between the apoptosis rates of all groups at the given sample times, except for the high levels in the toxic control. In vivo the urothelial cells survived on the polymers for 12 weeks with no adverse reactions in any of the mice. CONCLUSIONS: CO-alkene polymers are biocompatible materials for urothelial cells in vitro and in vivo, and thus are potential biomaterials for the urogenital tract.

Alkenes↗

PubMed1997

Influence of polymers for use in saliva substitutes on de- and remineralization of enamel in vitro.

A number of polymers which have previously been tested for their applicability as thickening agents in saliva substitutes were studied in vitro for their caries-protective properties. These were: polyacrylic acid, carboxymethylcellulose, xanthan gum, guar gum, hydroxyethylcellulose and porcine gastric mucin. The polymers were tested for their effects on: (1) growth of hydroxyapatite crystals in a supersaturated calcium phosphate solution, (2) dissolution of hydroxyapatite crystals in 50 mM acetic acid, pH 5.2 and (3) demineralization and remineralization of bovine enamel in a pH-cycling model. Growth of hydroxyapatite crystals was strongly inhibited by polyacrylic acid and carboxymethylcellulose at very low concentrations (0.005% w/v). Other polymers displayed lower inhibition of hydroxyapatite crystal growth. Hydroxyapatite dissolution was inhibited by all polymers except by hydroxymethylcellulose and xanthan gum. This occurred both in the presence of the polymers as well as after a 30-min preincubation. In the pH-cycling experiment, bovine enamel specimens with preformed lesions were alternately exposed to a demineralization buffer and a remineralization buffer containing the polymers hydroxyethylcellulose, carboxymethylcellulose, xanthan gum, polyacrylic acid, or porcine gastric mucin. A remineralization buffer containing 1 ppm NaF was used as a positive control. Under the experimental conditions, the control experiment without additives resulted in a net mineral loss (30.6 mumol Ca/cm2 after 14 days of pH cycling). In the presence of 1 ppm NaF, a small mineral gain was observed (8.6 mumol/cm2). All polymers largely inhibited further demineralization (1.2-12.3 mumol/cm2) except polyacrylic acid which, inhibited of its high calcium-binding capacity, caused demineralization, especially in the remineralization buffer (17.1 mumol/cm2). In conclusion, polymers tested in this study, except the polyacrylic acid, reduced the demineralization of enamel in vitro. The precise mechanism of the protective effect is not clear but it is speculated that formation of an absorbed polymer layer on the hydroxyapatite or enamel surface may provide protection against acidic attacks.

Acetic Acid↗