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PubMed2003

The surgical bed after BCNU polymer wafer placement for recurrent glioma: serial assessment on CT and MR imaging.

OBJECTIVE: The objective of our study was to describe the CT and MR imaging appearances of the surgical bed in the brains of patients receiving biodegradable polymers impregnated with N, N'1, 3-Bis-(2-chloroethyl)-N-nitrosourea (BCNU) for recurrent glioma and to determine whether patients receiving placebos could be differentiated from those receiving BCNU based on the pattern and growth kinetics of tumor recurrence. MATERIALS AND METHODS: The CT and MR images of 20 patients who underwent surgery for resection of recurrent high-grade gliomas and placement of intratumoral wafers (11 received BCNU polymer wafers, nine received control wafers) were analyzed for wafer appearance, volume of gas in the tumor bed, and volume of enhancement on serial scans. RESULTS: Wafers appeared as linear hyperdense structures on CT and as linear low-signal-intensity structures on MR imaging and caused no significant enhancement. In the BCNU polymer group, gas volume was 4.0 +/- 3.4 cm(3) (mean +/- SD), whereas gas volume was 1.6 +/- 3.0 cm(3) for the placebo group (Mann-Whitney test, p = 0.03). A trend toward linear rather than exponential recurrent tumor growth was identified for the BCNU polymer group but not for the placebo group. CONCLUSION: BCNU polymer wafers have a specific appearance on CT and MR imaging with which radiologists should be familiar: gas in the surgical bed is an expected transient finding, and tumor regrowth in patients receiving BCNU polymer wafers appeared to occur at a slower rate than in those receiving the placebo.

Adult↗

PubMedDate not supplied

In vitro-in vivo evaluation of bacampicillin hydrochloride from microcapsules of water-insoluble and an acid-soluble polymer.

Bacampicillin hydrochloride has been microencapsulated to mask its very bitter taste. The objective of the study was to compare the in vitro release and bioavailability of bacampicillin hydrochloride from microcapsules coated with two principally different polymers: a water-insoluble polymer, ethylcellulose, and an acid-soluble polymer, Eudragit E 100. The last mentioned was supposed to have advantages from a bioavailability point of view since this polymer should dissolve rapidly upon reaching the stomach. In vitro release studies were performed in different types of media by using a flow-through cell technique and USP paddle apparatus. The in vivo study was performed on 20 healthy volunteers taking single 400 mg doses of the drug in the two microcapsule suspensions and a reference tablet according to a randomized cross-over design. When standard dissolution fluids were used, the Eudragit E 100-coated microcapsules revealed very rapid dissolution but were greatly dependent on buffer concentration and ionic strength. The ethylcellulose-coated microcapsules released the drug much more slowly than Eudragit E 100 when using standard dissolution fluids. They were also affected by buffer concentration and ionic strength. The reference tablet had a significantly higher bioavailability than the two microcapsule suspensions. In vitro-in vivo correlation was not obtained when using standard dissolution fluids according to USP. However when stimulated intestinal fluid was adjusted to have an ionic strength similar to intestinal fluid, a better in vitro-in vivo correlation was obtained. The Eudragit E 100 polymer did not give better bioavailability than ethylcellulose as a coating polymer on bacampicillin microcapsules.

Absorption↗

PubMed1997

A long-circulating co-polymer in "passive targeting" to solid tumors.

A co-polymer of O-methyl polyethylene(glycol)-O'-succinate (MPEGs, m.w. 5100) and poly-l-lysine (PL, median m.w. 32700, degree of polymerization 256) has been synthesized by covalent grafting. The resultant MPEGs-PL (30% modification degree of epsilon-amino groups) had a hydrodynamic diameter corresponding to a 690 kD protein. Free amino groups (180/mol of the co-polymer) were used for conjugation of diethylene pentaacetic or succinic acid residues to MPEGs-PL. The potential of the resultant compound as a carrier of therapeutic and diagnostic drugs was studied using a rodent carcinoma models. The co-polymer had a blood pool half-life of 36h in adenocarcinoma-bearing rats. Radioactively labeled preparations were resistant to trans-chelation with apotransferrin and stable in blood for 24 h. The co-polymer accumulated in solid tumors at the level of 1.5-2% injected dose/g of tumor in 24 h. At that time, 34-40% of the accumulated polymer was associated with tumor cell fraction. The co-polymer non-covalently associated with cis-diamminedichloroplatinum(II), showed a cytostatic effect against mouse F9 carcinoma, and induced a reversal in tumor growth after intravenous administration.

Animals↗

PubMed1990

Effects of drag reducing polymer on atherosclerosis.

In order to determine the effect of drag reducing polymers on the occurrence of atherosclerosis, the Guinea pigs were used as the experimental animals. The inhibitory effect of a drag reducing polymer (polyacrylamide) on atherosclerosis in the aortas of Guinea pigs on a high cholesterol diet (2%) was investigated over a period of 6 months. The aortas, livers, kidneys and lungs of the animals, which were separated into four experimental groups (control, polymer, cholesterol and cholesterol + polymer) were also investigated both macroscopically and light microscopically. The selected physiological parameters such as, plasma cholesterol levels, plasma hemoglobin, hematocrit and total lipid values were determined at regular intervals for each group. The results indicate that the atherosclerosis in aorta of the animals receiving the polymer injection is suppressed significantly and the drag reducing water soluble polymers may be effectively applied against atherosclerosis.

Acrylic Resins↗

PubMed2000

Epithelialization of a synthetic polymer in the feline cornea: a preliminary study.

PURPOSE: This study examined the potential of a synthetic polymer to support stable epithelial growth when implanted in the feline cornea. METHODS: A perfluoropolyether-based polymer was cast into lenticules that were coated with collagen I and implanted in four feline corneas. Epithelial growth onto the lenticules was monitored clinically for 6 weeks, after which time the animals were killed, and three corneas were evaluated histologically. Immunohistochemistry was used to identify proteins associated with the formation of a basement membrane (laminin) and adhesion complexes (bullous pemphigoid antigen and collagen VII). Electron microscopy was used to examine the tissue-polymer interface for evidence of the assembly of these adhesive structures. RESULTS: Postoperative epithelial growth began on days 2 to 3, and lenticules were fully epithelialized by days 5 to 9. Lenticules were clinically well tolerated and histology showed epithelium consisting of multiple layers adherent to the lenticule's surface. Laminin, bullous pemphigoid antigen and collagen VII were identified at the tissue-polymer interface using immunohistochemistry. Ultrastructural examination showed evidence of assembly of these proteins into a recognizable basement membrane and hemidesmosomal plaques. CONCLUSIONS: A perfluoropolyether-based polymer coated with collagen I was implanted in the feline cornea and supported epithelial growth that showed signs of persistent adhesion, both clinically and histologically. This polymer shows potential for ophthalmic applications that require sustained epithelialization.

Animals↗

PubMed2001

"Synthetic Metals": A Novel Role for Organic Polymers (Nobel Lecture) Copyright((c)) The Nobel Foundation 2001. We thank the Nobel Foundation, Stockholm, for permission to print this lecture.

Since the initial discovery in 1977, that polyacetylene (CH)(x), now commonly known as the prototype conducting polymer, could be p- or n-doped either chemically or electrochemically to the metallic state, the development of the field of conducting polymers has continued to accelerate at an unexpectedly rapid rate and a variety of other conducting polymers and their derivatives have been discovered. Other types of doping are also possible, such as "photo-doping" and "charge-injection doping" in which no counter dopant ion is involved. One exciting challenge is the development of low-cost disposable plastic/paper electronic devices. Conventional inorganic conductors, such as metals, and semiconductors, such as silicon, commonly require multiple etching and lithographic steps in fabricating them for use in electronic devices. The number of processing and etching steps involved limits the minimum price. On the other hand, conducting polymers combine many advantages of plastics, for example, flexibility and processing from solution, with the additional advantage of conductivity in the metallic or semiconducting regimes; however, the lack of simple methods to obtain inexpensive conductive polymer shapes/patterns limit many applications. Herein is described a novel, simple, and cheap method to prepare patterns of conducting polymers by a process which we term, "Line Patterning".

Journal Article↗

PubMed1999

[A water-soluble synthetic polymer, alpha,beta-poly(hydroxyalkyl)-DL-asparamide, and conjugating drug].

A water-soluble polymer alpha,beta-poly (hydroxyalkyl)-DL-asparamide was synthesized by polysuccinimide(PSI) and different lengths of hydroxyalkyls, including alpha,beta-poly(hydroxyethyl)-DL-asparamide(PHEA), alpha,beta-poly(hydroxypropyl)-DL-asparamide(PHPA), and alpha,beta-poly(hydroxybutyl)-DL-asparamide(PHBA). These polymers were characterized by differential scanning calorimetry(DSC) and infrared spectrophotometry(IR). Stability and acutetoxicity of these polymers were studied. The experiment indicated that these materials were of low-toxicity and high stability. Acetylsalicylic acid, as a model drug, was conjugated into polymers; the drug loadings were 38.63%, 37.68% and 38.70% respectively. Polymer drugs were made into cylinder, and in-vivo release in rabbits was set out. It showed that the longer the spacer was linked into the polymer, the faster the drug was released.

Animals↗

PubMedDate not supplied

Fibronectin surface density affects endothelial cell function and growth on hydrophilic polymer.

Adhesive biomolecules have been used to promote endothelial cell adherence to polymer surfaces. The authors varied the surface density of one such biomolecule (fibronectin) applied to a hydrophilic polymer in an in vitro model system and then measured the amount of prostaglandin E2 (PGE2) produced by endothelial cells grown on these modified polymers. Endothelial cells grown on polymers with fibronectin applied at a surface density of 10 and 35% produced significantly more PGE2 (25.7 +/- 2.1 and 26.8 +/- 0.9 pg, respectively) than cells grown on polymer with no fibronectin (7.3 +/- 1.0 pg) and with complete saturation of the polymer surface with fibronectin (13.1 +/- 5.3 pg), with a p less than 0.005 for the comparison. The surface density of biomolecules on an artificial substrate is an important determinant of endothelial cell function.

Animals↗

PubMed1990

A human leukemia cell culture system for testing new antifols: differential sensitivity of lymphoid and nonlymphoid cell lines to unconjugated and methotrexate-conjugated polymers of basic amino acids.

A human cell culture system is described for biological testing of potent new folate-targeted antileukemic drugs that are poorly transported. Basic amino acid (lysine and ornithine) polymers were employed as carriers for increasing the uptake of folate analogs by human leukemia cell lines. In growth inhibition assays, the lymphocytic CCRF-CEM line displayed sensitivities to covalent methotrexate (MTX) conjugates of poly-L-lysine (Mr = 15,000, 50,000, or 100,000) or poly-L-ornithine (Mr = 35,000) which were identical to the sensitivities of these cells to the unconjugated polymers during continuous (120 hr) and pulse (24 hr) exposures; both polymers and conjugates were 50-fold less toxic than unconjugated MTX. The growth inhibitory effects of the polymers or MTX-conjugates were not reversed by simultaneous inclusion of leucovorin, while those of MTX were reversed. In contrast, the nonlymphocytic K562 line showed toxicity by the MTX-conjugates at nontoxic levels of the polymers during continuous, but not pulse, exposures. During continuous exposure the conjugates were only 10-fold less toxic than unconjugated MTX. Toxicities of the MTX-conjugates for the K562 line under continuous exposure conditions were reversed by the simultaneous presence of leucovorin or the lysosomotropic agent leupeptin and thus appeared to be a true antifolate effect which required uptake and lysosomal degradation. This human cell line is thus a suitable system in which to study the effects of antifolates which can be coupled to basic polymers.

Blood Physiological Phenomena↗

PubMed1990

A new concept of fibrin formation based upon the linear growth of interlacing and branching polymers and molecular alignment into interlocked single-stranded segments.

In a previous electron microscopic study of early fibrin polymers processed by freeze drying and rotatory shadowing, a large proportion of loosely constructed, frequently branching linear molecular chains was observed; their structural organization was inconsistent with a half-staggered double-stranded model for fibrin polymerization. These conflicting results prompted us to investigate the structure of early fibrin polymers prepared according to a large variety of methods currently used for electron microscopy of macromolecules. By use of a systematic random sampling procedure, fibrin polymers were photographically recorded. They were classified according to their morphological form, and the frequency of occurrence of each configuration was determined. Half-staggered double-stranded forms accounted for less than 1% of all types encountered. Interpretation of the structural organization manifested in the diverse polymer forms observed necessitated the construction of a new interlocked single-strand model for fibrin polymerization. The fibrin polymerization process combines simultaneous propagation of linear growth, branching, and lateral interlocking (leading to lateral association), resulting in the rapid formation of a fibrin network. The structural pattern developing during growth of fibrin polymers appears to be determined principally by the enzymatic mechanism and not solely by the intrinsic molecular structure of fibrinogen. The validity of the interlocked single-strand model was tested by selective fibrinopeptide-B-releasing experiments. Under such activation conditions, the polymer forms predicted according to this and the half-staggered double-strand models should differ; the structures observed were indeed consistent with the interlocked single-strand hypothesis. The compatibility of existing data with this model is discussed.

Fibrin↗

PubMed1986

Polyethylene glycol polymers of low molecular weight as probes of intestinal permeability. I. Innovations in analysis and quantitation.

The differential passive permeation of polymers of different lengths across the intestinal mucosa has been proposed as a probe to test mucosal integrity under a variety of physiologic and pathologic conditions. Polyethylene glycol (PEG) 400 contains a series of polymers whose pattern of urinary recovery after oral administration has been used to characterize intestinal mucosal function. To extend this method to the low levels of PEG polymers found in the urine of children with diarrhea, we have introduced three methodologic innovations. These alterations involve (1) formulation of a balanced PEG polymer mixture, (2) improved isolation, derivatization, and gas chromatography techniques, and (3) a new quantification of the pattern of PEG urinary recoveries. Urinary recovery of orally administered PEG was assessed in four normal adults, six hospitalized infants without gastrointestinal complains, two infants with prolonged diarrhea and carbohydrate malabsorption, and two children with cystic fibrosis. A parameter characterizing the urinary recovery of PEG, N1/2, which is the theoretical number of subunits in the polymer whose recovery is reduced to 50% of the value of the polymer whose recovery is maximal, gave stable, reproducible, and consistent results in normal adults and infants.

Adult↗

PubMed1983

Mechanisms for the spontaneous formation of covalently linked polymers of the terminal membranolytic complement protein (C9).

Purified human C9 spontaneously polymerizes upon prolonged incubation at 37 degrees C, and a fraction of these C9 polymers becomes resistant to dissociation by sodium dodecyl sulfate (SDS) and reducing agents. We examined possible mechanisms for this spontaneous covalent linking of C9. The following results are consistent with the conclusion that the formation of the covalently linked C9 polymer involves disulfide linking. 1) In addition to the SDS/dithiothreitol (DTT)-resistant C9 polymer (Mr = 950,000), disulfide-linked C9 dimers and trimers were formed upon incubation of C9 at 37 degrees C for 64 h. 2) The C9 polymer formed upon incubation at 37 degrees C for 64 h was resistant to dissociation by 6 M guanidine hydrochloride, 20 mM DTT but was dissociated by 6 M guanidine thiocyanate alone, yielding disulfide-linked C9 oligomers. 3) The formation of the SDS/DTT-resistant C9 polymer was completely inhibited by 1 mM iodoacetamide and 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), while DTNB enhanced the formation of disulfide-linked C9 oligomers. 4) A significant amount of free sulfhydryl group was detected in the polymerized C9 samples with various SH-specific reagents, though native C9 reacted with none of these reagents. In addition, inhibition by 1 mM iodoacetamide of C9 disulfide linking inhibited the self-association of C9 as analyzed by gel filtration on TSK-G4000 SW, whereas enhancement by 1mM DTNB of C9 disulfide linking enhanced C9 self-association. Thus, these results indicate that C9 disulfide linking that occurs upon C9 polymerization is an intrinsic property of C9 which is of importance in the formation of the stable C9 polymer structure.

Complement C9↗

PubMed1994

Computer modelling of polymer decomposition by active interactions with enzyme molecules. A simulation of RNA digestion by ribonuclease.

A model of 200 polymer molecules each 70 units of length with randomly located susceptible and resistant links was elaborated. The production of mono-, di-, tri-unit and other fragments in repeating random interactions of polymer (P) with the polymer--cleaving enzyme (E) was calculated. Analysis of the calculations performed that the polymer molecules with an initial count of 70-units disappeared, imitating the first order kinetics with a half-life of about 0.37 x 10(3) P/E interactions. The production of fragments 30-69 units long was small and the life of those molecules was limited to a range from 0.5 x 10(3) to 5 x 10(3) P/E interactions. The mean polymer length decreases to one third at 10(3) P/E interactions. The production of single-unit fragments followed a sigmoidal relationship. The first reaction period, with increasing number of single-unit fragments per 10(3) P/E interactions, corresponded to a decrease in the mean polymer length to about 10 units. Then the production of one-unit fragments decreased and stopped at about 10(5) P/E interactions. This model could be used for analysis of RNA fragmentation processes by any number of RNA-ribonuclease interactions. Further development of this model would be of help in understanding the effect of various nucleotide sequences on the RNA digestion process.

Animals↗

PubMedDate not supplied

Rheological characterization of cellulosic and alginate polymers.

The purpose of this study was to assess the properties of aqueous solutions of various polymeric materials intended for use as components of a sustained release device for various proteins. Polymers that were studied included Sodium Carboxymethylcellulose (CMC), Methylcellulose (MC), Hydroxypropylmethylcellulose (HPMC) and Sodium Alginate (ALG). The effects of polymer concentration, temperature and autoclaving on solution viscosity were determined. With all the polymers, viscosity/ concentration relationships were linearized by using an equation of the type mu = (Ca + beta)gamma, where mu and C referred to solution viscosity and concentration, respectively. alpha and gamma were constants related to polymer type and molecular weight, whereas beta reflected viscosity of water at the temperature of measurement. gamma, which reflects the sensitivity of the viscosity/concentration relationship, was determined to be 4 for both low and high molecular weight CMC and ALG, and 8 for MC and HPMC. alpha, on the other hand, was directly proportional to polymer molecular weight. The same equation could also adequately describe viscosity/temperature relationships for each polymer. For both CMC and ALG, increasing solution concentration had a greater effect on the reduction of viscosity upon increasing temperature. A concentration dependent thermal "gelation" phenomena was observed with MC solutions. Autoclaving effects were more pronounced in ALG solutions as compared to CMC samples in the 0.5 to 3.0% w/v concentration range. No significant long term effects on solution viscosity were observed with MC and HPMC, however.

Alginates↗

PubMed2005

Design and fabrication of a largely deformable sensorized polymer actuator.

Polypyrrole (PPy), with its biomimetic properties such as high power density, large strain, and biocompatibility, is an excellent candidate for a biomimetic microactuator in microrobotics and bioengineering. A polyvinylidene fluorid (PVDF) sensor is also biocompatible, flexible, and chemically stable. Therefore, a PPy actuator is integrated with a PVDF sensor to realize a sensorized polymer actuator. A novel sensorized polymer actuator can accurately measure its bending motion precisely with real time. Experimental results demonstrate the feasibility of the sensorized polymer actuator. The polymer actuator can be actuated while it senses signals induced from the bending motion. In addition, the position of the sensorized polymer actuator can be controlled and adjusted precisely with feedback signals from its embedded sensor at the time of operation. If this system becomes more robust and reliable, its applications are promising and can be realized in cell handling, microrobotics, and microsurgery with the integration of standard microfabrication techniques.

Biocompatible Materials↗

PubMed2005

Electroactive polymeric sensors in hand prostheses: bending response of an ionic polymer metal composite.

In stark contrast to the inspiring functionality of the natural hand, limitations of current upper limb prostheses stemming from marginal feedback control, challenges of mechanical design, and lack of sensory capacity, are well-established. This paper provides a critical review of current sensory systems and the potential of a selection of electroactive polymers for sensory applications in hand prostheses. Candidate electroactive polymers are reviewed in terms of their relevant advantages and disadvantages, together with their current implementation in related applications. Empirical analysis of one of the most novel electroactive polymers, ionic polymer metal composites (IPMC), was conducted to demonstrate its potential for prosthetic applications. With linear responses within the operating range typical of hand prostheses, bending angles, and bending rates were accurately measured with 4.4+/-2.5 and 4.8+/-3.5% error, respectively, using the IPMC sensors. With these comparable error rates to traditional resistive bend sensors and a wide range of sensitivities and responses, electroactive polymers offer a promising alternative to more traditional sensory approaches. Their potential role in prosthetics is further heightened by their flexible and formable structure, and their ability to act as both sensors and actuators.

Artificial Limbs↗

PubMed1987

Adult human vascular endothelial cell attachment and migration on novel bioabsorbable polymers.

We studied the ability of polymers from which vascular prostheses (VPs) are or could be fabricated to support attachment and migration of adult human vascular endothelial cells (AHVECs) in an in vitro system. Polymers included Mylar, Teflon, two novel bioabsorbable polymers with different biologic half-lives (BR1 and BR2), and an elastic nonabsorbable biocompatible polymer (EBN). Both BR1, BR2, and EBN supported AHVEC attachment well (56%, 62%, and 71%, respectively, of plated cells at one hour, respectively) but differed in their ability to support AHVEC migration. The AHVECs attached less well to Mylar and Teflon (39% and 21%), and in no case were AHVECs observed to grow or migrate on either of these polymers. This finding correlates with the clinical observation that VPs fabricated from Mylar and Teflon uniformly fail to develop an endothelial cell lining after implantation in vivo. Future VPs, fabricated from materials chosen for their ability to support AHVEC attachment, growth, and migration in vitro, might better support a spontaneous endothelial cell lining after implantation in humans.

Adult↗

PubMed1999

Behavior of blood cells in contact with water-soluble phospholipid polymer.

Omega-Methacryloyloxyalkyl phosphorylcholine (MAPC) polymer, which has various methylene chain lengths between the phosphorylcholine group and the backbone, was synthesized with attention to formation of the biomembrane. The effect of water-soluble poly(MAPC) on the function and activation of blood cells was evaluated to determine the interaction between blood cells and the MAPC polymer. The poly(MAPC) and the MAPC copolymer with a small amount of fluorescent units were synthesized by a conventional radical polymerization technique. Using a fluorescence spectrometer, it was determined that the MAPC polymer was adsorbed on the plasma membrane of platelets when the platelets were suspended in an aqueous solution of the MAPC copolymer. The hemolytic activity of poly(MAPC) was less than that of other water-soluble polymers, such as poly(ethylene glycol) and poly(1-vinyl-2-pyrrolidone) (PVPy). The change in the plasma membrane fluidity of platelets on contact with poly(MAPC) was determined with 1,6-diphenyl-1,3,5,-hexatriene. The plasma membrane fluidity of platelets decreased with an increase in the methylene chain length of the MAPC unit. The aggregation activity of platelets after contact with poly(MAPC) was also evaluated, but no significant difference between that of polymer-contacted platelets and native platelets was observed. Finally, the activity of platelets on contact with poly(MAPC) was determined by measuring the cytoplasmic calcium ion concentration ([Ca2+]i) in platelets. The increase in [Ca2+]i in the platelets after contact with poly(MAPC) was similar to that of native platelets. We conclude that the poly(MAPC) reduced platelet activation even though the poly(MAPC) adsorbed on the membrane surface of the platelets. In particular, poly(10-methacryloyloxydecyl phosphorylcholine) significantly reduced platelet activation compared with PVPy.

Adsorption↗