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PubMed1991

Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas.

Malignant gliomas have been difficult to treat with chemotherapy. The most effective agent, BCNU (carmustine), has considerable systemic toxicity and a short half-life in serum. To obviate these problems, a method has been developed for the local sustained release of chemotherapeutic agents by their incorporation into biodegradable polymers. Implantation of the drug-impregnated polymer at the tumor site allows prolonged local exposure with minimal systemic exposure. In this Phase I-II study, 21 patients with recurrent malignant glioma were treated with BCNU released interstitially by means of a polyanhydride biodegradable polymer implant. Up to eight polymer wafers were placed in the resection cavity intraoperatively, upon completion of tumor debulking. The polymer releases the therapeutic drug for approximately 3 weeks. Three increasing concentrations of BCNU were studied; the treatment was well tolerated at all three levels. There were no adverse reactions to the BCNU wafer treatment itself. The average survival period after reoperation was 65 weeks for the first dose group, 64 weeks for the second dose group, and 32 weeks for the highest dose group. The overall mean survival time was 48 weeks from reoperation and 94 weeks from the original operation. The overall median survival times were 46 weeks postimplant and 87 weeks from initial surgery. Eighteen (86%) of 21 patients lived more than 1 year from the time of their initial diagnosis and eight (38%) of 21 patients lived more than 1 year after intracranial implantation of the polymer. Frequent hematology, blood chemistry, and urinalysis tests did not reveal any systemic effect from this interstitial chemotherapy. Since the therapy is well tolerated and safe, a placebo-controlled clinical trial has been started. The trial will measure the effect of the second treatment dose on survival of patients with recurrent malignant glioma.

Brain Neoplasms↗

PubMed1992

Direct thrombosis of aneurysms with cellulose acetate polymer. Part I: Results of thrombosis in experimental aneurysms.

The authors have developed a liquid material for thrombosing aneurysms. This material is a mixture of cellulose acetate polymer and bismuth trioxide dissolved in dimethyl sulfoxide. On contact with blood, the dimethyl sulfoxide diffuses and cellulose acetate polymer forms, which balloons when slowly injected into the blood. The polymer solidifies from surface to core in 5 minutes. Cellulose acetate polymer was injected directly into experimental aneurysms created in 10 dogs; it rapidly hardened in the shape of the aneurysms, completely obliterating them but preserving the parent vessels in all cases. No distal migration of the polymer was seen. The good results of this experimental trial led to a clinical study using a cellulose acetate polymer, as described in Part II.

Aneurysm↗

PubMed2001

Health effects following chronic dosing with tungsten-iron and tungsten-polymer shot in adult game-farm mallards.

Permanent approval of shot composed of tungsten-iron and tungsten-polymer for waterfowl hunting by the U.S. Fish and Wildlife Service was pending the results of the present study that examined the health and reproductive effects of the two shot types on mallards (Anas platyrhynchos) over a 150-day period. We collected data pertaining to the effects of tungsten-iron and tungsten-polymer shot on mortality, body weight, organ weight, tissue pathology, and shot erosion. Thirty-two bird groups (sexes equal) of adult mallards were dosed orally with eight #4 steel shot (control), eight #4 tungsten-iron shot, or eight #4 tungsten-polymer shot on days 0, 30, 60, 90, and 120 of a 150-day trial (26 January 1998 to 25 June 1998). An additional 12 mallards (sexes equal) were dosed orally with eight #4 lead shot (positive control) on day 0 of the study. All lead-dosed ducks died by day 25, whereas no ducks died in the other treatment groups. Significant liver hemosiderosis was present in all control and tungsten-iron-dosed males, in five of eight control and three of eight tungsten-iron-dosed females, and in one tungsten-polymer-dosed male examined. The rate of shot erosion was highest for tungsten-polymer shot (99%), followed by tungsten-iron (72%), and steel (55%) shot. Tungsten-iron or tungsten-polymer shot repeatedly administered to adult mallards did not have deleterious health effects during the 150-day trial based on mortality, body weights, organ weights, and histology of the liver and kidneys.

Alloys↗

PubMed2001

Reproductive effects and duckling survivability following chronic dosing with tungsten-iron and tungsten-polymer shot in adult game-farm mallards.

Tungsten-iron and tungsten-polymer shot were given conditional approval for waterfowl hunting by the U.S. Fish and Wildlife Service based partly on the results of a 30-day acute toxicity trial utilizing mallards (Anas platyrhynchos). Final approval of the two tungsten-containing shot was contingent on the results of a 150-day study that assessed the health and reproductive effects of tungsten-iron and tungsten-polymer shot in adult mallards. Reproductive data are presented in this paper. Sixteen male and 16 female adult mallards were dosed orally with eight #4 steel shot (control), eight #4 tungsten-iron shot, or eight #4 tungsten-polymer shot on days 0, 30, 60, 90, and 120 of a 150-day trial (26 January 1998 to 25 June 1998). Reproductive performance was assessed during the last 90 days (day 61 to day 150) of the trial. There were no significant differences in egg production and fertility and hatchability of eggs from tungsten-iron- and tungsten-polymer-dosed ducks compared to control ducks. There was no evidence of differences in percent survivability and body weight of ducklings from tungsten-iron and tungsten-polymer mallards compared to ducklings from control ducks. Tungsten-iron or tungsten-polymer shot repeatedly administered to adult mallards during the 150 day trial did not adversely affect reproduction or their offspring.

Animals↗

PubMed1998

Optimizing seeding and culture methods to engineer smooth muscle tissue on biodegradable polymer matrices.

The engineering of functional smooth muscle (SM) tissue is critical if one hopes to successfully replace the large number of tissues containing an SM component with engineered equivalents. This study reports on the effects of SM cell (SMC) seeding and culture conditions on the cellularity and composition of SM tissues engineered using biodegradable matrices (5 x 5 mm, 2-mm thick) of polyglycolic acid (PGA) fibers. Cells were seeded by injecting a cell suspension into polymer matrices in tissue culture dishes (static seeding), by stirring polymer matrices and a cell suspension in spinner flasks (stirred seeding), or by agitating polymer matrices and a cell suspension in tubes with an orbital shaker (agitated seeding). The density of SMCs adherent to these matrices was a function of cell concentration in the seeding solution, but under all conditions a larger number (approximately 1 order of magnitude) and more uniform distribution of SMCs adherent to the matrices were obtained with dynamic versus static seeding methods. The dynamic seeding methods, as compared to the static method, also ultimately resulted in new tissues that had a higher cellularity, more uniform cell distribution, and greater elastin deposition. The effects of culture conditions were next studied by culturing cell-polymer constructs in a stirred bioreactor versus static culture conditions. The stirred culture of SMC-seeded polymer matrices resulted in tissues with a cell density of 6.4 +/- 0.8 x 10(8) cells/cm3 after 5 weeks, compared to 2.0 +/- 1.1 x 10(8) cells/cm3 with static culture. The elastin and collagen synthesis rates and deposition within the engineered tissues were also increased by culture in the bioreactors. The elastin content after 5-week culture in the stirred bioreactor was 24 +/- 3%, and both the elastin content and the cellularity of these tissues are comparable to those of native SM tissue. New tissues were also created in vivo when dynamically seeded polymer matrices were implanted in rats for various times. In summary, the system defined by these studies shows promise for engineering a tissue comparable in many respects to native SM. This engineered tissue may find clinical applications and provide a tool to study molecular mechanisms in vascular development.

Animals↗

PubMed1996

Evolution of hydrogel polymers as contact lenses, surface coatings, dressings, and drug delivery systems.

Hydrogel polymers are hydrophilic resins that display excellent biocompatibility, which has allowed their application in diverse fields of surgery and medicine. The original hydrogel polymer, a copolymer of 2-hydroxyethyl methacrylate and ethylene dimethacrylate, was developed by Wichterle and Lim in 1954. The development of the first soft hydrogel contact lenses by Wichterle in 1961 represented the first successful clinical application of hydrogel polymers and remains one of the most important uses of hydrogels today. The biocompatibility of hydrogel polymers may be adapted to diverse tissue types by small variations in the makeup of the polymer, including varying the type and amount of monomers and differing the amounts and characteristics of the cross-linking agents used to create the polymer chains. Hydrogels have been successfully developed for use as coatings, soft contact lenses, wound dressings, and drug delivery systems.

Bandages↗

PubMed1999

Biodegradable polymer film as a source for formation of human fetal retinal pigment epithelium spheroids.

PURPOSE: To evaluate the attachment of human fetal rctinal pigment epithelial (HFRPE) cells to a biodegradable polymer film with subsequent formation of spheroids in vitro. METHODS: Ten biodegradable polymer films with different compositions were examined for their physical properties and ease of manipulation under a dissecting microscope. The film with the most suitable handling characteristics was chosen, and a purely isolated sheet of HFRPE cells was attached to it. The purity of the cells was assessed by their pigmentation and expression of cytokeratin. Proliferation was assessed by incorporation of 5-bromo-2'-deoxyuridine (BrdtJ). Cellular structure was analyzed under light and electron microscopes, and the functional capability of the cells was evaluated by rod outer segment (ROS) phagocytosis. RESULTS: The polymer film with composition 50:50 poly (DL-lactide) (PLA)/poly (DL-lactide-co-glycolide) (PLG) with an inherent viscosity of 1.03 dl/g was found to be the most suitable for handling under the microscope. Sheets of HFRPE cells attached to the polymer films within 48 hours and began to form spheroids. All the isolated cells were pigmented and expressed cytokeratin. They possessed a cuboidal morphology, numerous apical microvilli, and no sign of dedifferentiation. HFRPE cells produced extracellular matrix (collagen filaments) on their basal side, filling the cavities of the polymer film. The cells subsequently proliferated, incorporated BrdU, migrated onto the culture plate to form monolayers, and phagocytized ROS. CONCLUSIONS: Biodegradable polymer films can be used as a scaffold for the adhesion of the HFRPE sheet and formation of spheroids. Spheroids represent a source of high density and well-differentiated HFRPE cells that are easy to transfer. Furthermore, the stricture of the membrane makes it suitable for additional applications.

Biodegradation, Environmental↗

PubMed1999

Anionic carbohydrate-containing polymers of cell walls in two streptoverticille genospecies.

The cell walls of two streptoverticille genospecies which belong to a historically isolated group of the genus Streptomyces contain anionic polymers of different structure. Streptomyces hachijoensis VKM Ac-191T and Streptomyces cinnamoneus subsp. azacoluta VKM Ac-606T assigned to one genospecies on the basis of DNA--DNA hybridization [5] contain 37% of an identical sugar-1-phosphate polymer. The repeating disaccharide units of the polymer, 2-amino-2-deoxy-alpha-D-glucopyranosyl-(1-->6)-2-acetamido-2-deoxy-al pha-D-glucopyranose, are linked at C-1 and C-6' by phosphodiester bonds. The cell walls of Streptomyces biverticillatus VKM Ac-891T and Streptomyces baldaccii VKM Ac-821T, members of another genospecies, contain about 30% 1,3-poly(glycerol phosphate) completely substituted by 2-amino-2-deoxy-alpha-D-glucopyranosyl residues at C-2. Due to the presence of an amino sugar with a free amino group in the repeating unit, the polymers exhibit neutral properties. Polymer structures were determined by chemical methods and NMR spectroscopy. The data indicate taxonomic specificity of anionic polymers in streptoverticille cell walls.

Carbohydrates↗

PubMed1999

A novel efficient enzyme-immobilization reaction on NH2 polymers by means of L-ascorbic acid.

A new enzyme-immobilization reaction by means of L-ascorbic acid (ASA) is described using NH(2) polymers based on cellulose or poly(vinyl alcohol) with the example of oxidoreductase enzymes. In this way, enzyme proteins such as glucose oxidase (GOD), glutamate oxidase, lactate oxidase, urate oxidase and peroxidase can be covalently fixed with a high surface loading to ultrathin and transparent NH(2)-polymer films if their surfaces are previously treated with an ASA solution, in, for example, N,N-dimethyl acetamide, DMSO or methanol. ASA then obviously reacts like a diketo compound with amino groups of the NH(2)-polymer film and enzyme protein, forming dehydroascorbic acid derivatives with neighbouring Schiff's-base structures. In a subsequent fragmentation reaction, the latter presumably form stable oxalic acid diamide derivatives as coupling structures between enzyme protein and NH(2)-polymer film, as suggested by results from investigations of the ASA reaction with n-butylamine. The immobilized enzymes can be stored at 4 degrees C in bidistilled water for at least 1 month without becoming detached from the NH(2)-polymer film and without diminished enzyme activity. The apparent K(m) values of the immobilized enzymes are in part clearly smaller than those of the dissolved enzymes or those found in other immobilization processes such as the diazo coupling or the bifunctional glutardialdehyde reaction. For example, the K(m) value of the immobilized GOD with different NH(2) polymers as the matrix structure is smaller by a factor of approx. 20 than that of the dissolved enzyme.

Acetamides↗

PubMed1975

The instilled fluid dynamics and surface chemistry of polymers in the preocular tear film.

Using slit lamp fluorophotometry it was demonstrated that the rate of drainage of a vehicle placed in the eye increased with increasing volume and that polymer solutions increased the thickness of the precorneal tear film (PTF). By increasing the viscosity of the delivery vehicle, (e.g., a hydroxypropylmethylcellulose polymer solutions), the PTF retention of fluorescein could be increased. The increased retention was shown to be due to an increase in the tear reservoir volume provided by the more viscous solutions. The PTF retention of fluorescein in a polyvinyl alcohol (PVA) vehicle was not as viscosity dependent, although PVA did seem to produce greater initial PTF fluorescence. This suggested that PVA initially produced a thicker PTF. The PTF retention of fluorescein by five commercial solutions did not have any relation to their wetting properties. The only good correlation with fluorescein retention in the PTF measured, seemed to be the ability of different polymer solutions to stabilize a thick layer of water as measured by the spontaneous spreading of polymer molecules at the air/liquid interface on wet glass surfaces. This model was designed to simulate tear film spreading in vivo. The results suggest that different polymer solutions may produce thicker PTF's than normal by virtue of their ability to drag water with them as they spread over the ocular surface with each blink. Mechanisms by which polymer solutions may increase the thickness of the PTF are discussed.

Animals↗

PubMed2001

Aerobic and anaerobic biodegradability of a flocculant polymer.

Flocculant polymers are used to improve the efficiency of separation processes used in wastewater treatment. The subsequent fate and effects of these additives are uncertain, however, with some previous reports indicating them to be biodegradable while others indicate complete recalcitrance. The biodegradability of a common flocculant polymer was therefore evaluated, using both aerobic and anaerobic batch assays. Knowledge of the polymer's chemical composition also allowed degradation stoichiometries to be calculated for complete biodegradation and also for incomplete degradation to several hypothesized end products. Results showed conclusively that the polymer was subject to partial degradation by both aerobic and anaerobic cultures. Measured oxygen consumption under aerobic conditions, and gas production under anaerobic conditions, both indicate that the partial destruction of pendant cationic moieties occurs, but that the polymer's CH2 backbone remains essentially intact. These results allow seemingly contradictory previous reports to be explained. The findings are relevant to the environmental fate of these polymers as well as certain treatment process effects.

Bacteria, Aerobic↗

PubMed2001

[Application of pH-responsive polymers to oral dosage forms for insulin].

The potential of graft copolymer networks with poly(methacrylic acid-g-ethylene glycol; P(MAA-g-EG)) for oral dosage forms to enhance insulin absorption is reviewed. The polymer exhibited unique pH-responsive characteristics in which interpolymer complexes were formed and dissociated, respectively, in acidic and neutral/basic environments. Correspondingly, the polymer was capable of highly incorporating and rapidly releasing insulin in vitro. This insulin loaded polymer successfully enhanced oral insulin absorption in rats with significant hypoglycemic effects. The polymer was also shown to possess mucoadhesive properties. Furthermore, the polymer demonstrated high calcium binding which may affect the proteolytic activity of calcium-dependent enzymes and/or reduce transepithelial resistances. Thus, the polymer has the potential to be used as a carrier for oral dosage forms of insulin to enhance its mucosal absorption.

Administration, Oral↗

PubMed2002

[Effects of polyacrylamide on settling and separation of oil droplets in polymer flooding produced water].

The research found anion polyacrylamide (HPAM) had positive and negative effects on oil-water separation. Polymer made oily wastewater's viscosity increase and reduce rising velocity, and polymer can also increase intensity of water films between oil droplets and lengthen coalescence time of oil droplets. Those were not in favor of settling and separation for oil droplets. The positive effects on separation were that polyacrylamide had flocculating activity and made small droplets contact each other and combine into big droplets. When polymer's molecular weight was 2.72 x 10(6), and concentration was less than 800 mg/L, polymer was in favor of oil droplets settling and separation. The prime reason for oily wastewater of polymer flooding difficult to dispose was that initial median diameters of oil droplets were small. The transverse flow oil separator can intensify oil droplets combination and shorten rising time. The locale experiments showed the separator was suitable for dealing with oily wastewater of polymer flooding.

Acrylic Resins↗

PubMedDate not supplied

Development and characterization of rosin-based polymer and its application as a cream base.

The literature contains many references to the wide range of uses of rosin-based polymers, but little has appeared in the area of rosin-based polymers used as cream bases. Various rosin polymers based on glycerol, sorbitol, and pentaerythritol were prepared and screened for efficacy as cream bases. Among these polymers, polymer 2 (glycerol-based) is reported in the present study as it produced creams with a better stability and release profile as compared to other creams. The creams were formulated employing polymer 2 (P2) and Tween 60 as surfactants. The stability of the prepared creams, as well as the diclofenac diethylammonium release pattern, was investigated using particle size analysis, conductivity, relative dielectric constant, spreadability, and irritation potential measurement, and was compared with that of creams containing Tween 60 (RT) prepared in the laboratory. The release of the drug, diclofenac diethylammonium, was measured after eight hours and compared with a standard cream (RT) and a marketed cream (RM).

Animals↗

PubMed2001

[Electrophoretic migration behavior of deoxyribonucleic acid fragments in three polymer solution concentration regions].

The theory of polymer coils shrinking in semi-dilute solution has recently been developed on polymer solution. The polymer solution from coils shrinking concentration Cs to uniform entangled concentt concentration C+ has been defined as semi-dilute solution. We experimentally investigated the electrophoretic migration behavior of 100 bp deoxyribonucleic acid (DNA) Ladder in hydroxypropyl methyl cellulose (HPMC) concentration ranging from 1.25 g/L to 16.06 g/L. The friction force mobility mu f is used to express the friction force that DNA will encounter in capillary electrophoresis. Our results indicate the division of polymer solution into three regions depending on the relationship of mu f and HPMC concentration and Ferguson plot. Resolutions of 200 bp/300 bp and 700 bp/800 bp show semi-dilute polymer solution suits large fragments and small fragments DNA separation respectively. the results confirm that the current polymer theory is valid under actual CE condition.

Attention↗

PubMedDate not supplied

New polymer alloy dialysis membranes with varying permeabilities and sievings.

The superstructure of polymer alloys that is responsible for their function is best controlled by varying the polymers, polymer blend ratio, solvents, temperature, or all four. Dialysis membranes made of polymer alloys can have varying pure water and solute permeabilities, pore sizes, pore size distributions, and mechanical strengths when wet. Resistance to heat and mass transfer can also vary. The optimal superstructure design of a polymer alloy dialysis membrane enables it to remove efficiently newly identified uremic toxins with higher molecular weights from patients on hemodialysis. The authors prepared new hollow fiber dialysis membranes using a polyethersulfone/polyacrylate (PEPA) polymer alloy, and evaluated pure water and solute permeabilities and reflection coefficients that are dependent upon the superstructure of the PEPA membranes. The new PEPA membranes are asymmetric, with skin layers on either side. The values for pure water permeability and overall mass transfer coefficients for urea, creatinine, and vitamin B12 are quite adequate for hemodialysis. The reflection coefficients for substances with molecular weights greater than 3,000 are strongly dependent upon the conditions under which the membranes were prepared. The values for cytochrome C permeability ranged from 0.42 to 0.71 microns/s.

Alloys↗

PubMed1992

Polymer-bound enzyme inhibitors: synthesis, properties, and physiological relevance.

For the most part, the pharmacological effect of an enzyme inhibitor results from its interaction with a single target molecule--the target enzyme. In many cases, the inhibitor moiety can interact effectively with the enzyme without necessarily being released from the polymer carrier. In the simplest form, i.e., the inhibition of an extracellular enzyme, this interaction can be understood as being two macromolecules in a solution--a reaction that can be readily modeled in vitro. Thus, enzyme inhibitors are very suitable for preparing polymer-bound drugs for investigative purposes or therapeutical applications. The macromolecular properties of polymers impact on the pharmacokinetic behavior of the compound because of the controlled intercompartmental transport. The physiological significance of the polymer-bound enzyme inhibitors is considered herein regarding the factors controlling the biodistribution of polymers among the physiological compartments. Extracellular proteinases and lysosomal enzymes are the most easily approachable targets. Strategies for preparation of polymer-bound inhibitors are discussed.

Animals↗

PubMed2004

Polymer therapeutics - Sixth International Symposium: from laboratory to clinical practice. Industrial development and clinical evaluation.

This biannual conference was organized, as is now customary, by Professor Ruth Duncan of the Welsh School of Pharmacy and focused on novel technology and pharmaceutical compounds in the area of polymer therapeutics. This meeting has established itself as an important interface between discovery research and preclinical and clinical development in this field. Sufficient time was allocated for informal interaction between the delegates, which allowed for plenty of discussion and initiation of collaboration. The emphasis in most presentations was on the use of polymers and dendrimers as active ingredients, or for conjugation with other entities for the purpose of improving drug properties such as pharmacodynamic (PD) and pharmacokinetic (PK) profile, drug handling, or targeting and delivery. Several talks and posters focused on novel and proven techniques for the biophysical characterization of polymer constructs and their metabolites. To date, the most successful therapeutic class are conjugates of polymers to protein drugs; six drugs are approved and approximately a dozen are in various stages of clinical development. However, several covalent and non-covalent conjugates of small-molecule cancer chemotherapy agents are now in more advanced clinical trials, and several other polymer constructs and dendrimers are in early clinical trials. This meeting clearly demonstrated that there are many promising approaches for the application of a variety of polymers, but that the viability of many of the approaches still needs to be proven in late-stage clinical trials as well as in the market place.

Animals↗