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PubMed1995

Hydrolytic degradation of benzylated poly(beta-malic acid): influence of sample size, sample shape, and polymer composition.

In order to investigate the effects of sample size, sample shape, and polymer composition on the hydrolytic degradation of water-insoluble benzylated poly(beta-malic acid) derivatives, three polymers were synthesized, namely PMLABe100, PMLABe90H10 and PMLABe80H20, containing 100, 90, and 80% of benzyl units respectively. For each polymer, 4-mm-thick compression molded pellets, 0.3-mm-thick casted films and 250-500 microns ground particles were made and allowed to age in 0.13 M, pH 7.4 sodium phosphate buffer at 37 degrees C. Degradation was monitored by measuring weight changes, variations of polymer composition, formation of benzyl alcohol, and molecular weight decreases. It was shown that degradation of particles and films depended initially on polymer composition due primarily to fast degradation of acid-rich segments present or formed by benzyl ester cleavages which led more or less rapidly to similar compositions for the three polymers. The higher the content in acid groups, the faster the degradation rate and the characteristic changes. It was also found that pellets made of PMLABe90H10 or PMLABe80H20 degraded heterogeneously and much faster than corresponding films and particles.

Benzene Derivatives↗

PubMed1994

Attempts to stabilize a monoclonal antibody with water soluble synthetic polymers of varying hydrophobicity.

Proteins are subject to a variety of physical and chemical reactions that lead to a loss of activity. These reactions are a particular problem in controlled-release devices, where temperatures and protein concentrations are high. Current approaches to increasing protein stability include the addition of saccharides, amino acids, or polymers. New synthetic polymers may be promising protein stabilizers because properties such as molecular weight and side-chain composition can be controlled. In this study, the stability of a murine monoclonal antibody, BR96, was evaluated in solution at 37 degrees C. The antibody was incubated in the presence of a series of synthetic polymers that included poly(glucosylethyl methacrylate) (GEMA) and copolymers of N-vinylpyrrolidone (NVP) and methyl methacrylate (MMA). Samples were taken periodically up to 30 days. The formation of precipitated antibody in particulate aggregates was measured with a Coulter counter, and the molecular-weight distribution of soluble antibody was measured by size-exclusion chromatography. Two trends were evident. First, with poly(GEMA) and copolymers of NVP and MMA, protein aggregation increased at higher polymer concentrations. Second, higher molecular weights of the poly(NVP) homopolymer also led to increases in protein aggregation. Effects of polymer hydrophobicity were more complex. A copolymer containing 9 mol% MMA caused immediate protein precipitation, while a copolymer containing 21 mol% MMA did not. The effects of the copolymer containing 21% MMA were strongly concentration dependent. At 1 wt%, the polymer reduced aggregation, but aggregation increased strongly between concentrations of 2 and 3 wt%.

Animals↗

PubMed1998

Creating biomimetic micro-environments with synthetic polymer-peptide hybrid molecules.

In designing polymers that can act as tissue engineering templates it is beneficial to consider methods of mimicking the natural support structures used by the human body to guide the behavior and development of cells within tissues. The well-known RGD cell adhesion ligand provides a simple mechanism of creating polymer surfaces that mimic the extracellular matrix. This paper considers the methods that have been used to attach such motifs to synthetic polymers. In general there are two strategies: the formation of polymer-peptide hybrid molecules, or the immobilization of the ligand on the fabricated surface of the polymer. The three major synthetic strategies of creating polymer-peptide hybrids are reviewed.

Biocompatible Materials↗

PubMed1998

Synthesis and characterization of polymer-(multi)-peptide conjugates for control of specific cell aggregation.

A new synthetic approach has been applied to obtain novel di-, tetra-, and (multi)-peptide containing polymer conjugates in quantitative yields with a high degree of conjugation. Bis-(N-hydroxysuccinimidyl) esters of PEG (Mw = 200, 600, 1400, 2000, and 3400) were synthesized and studied in a condensation reaction with synthetic peptides: glycine-glycine-tyrosine-arginine (GGYR), a model peptide, and glycine-arginine-glycine-aspartic acid-tyrosine (GRGDY), a sequence known to promote cell adhesion and aggregation. Tetra-substituted derivatives of PEG-based conjugates were synthesized by coupling L-aspartic acid and L-aspartyl-L-phenylalanine through a condensation procedure in organic media. Poly(acrylic acid) and co-polymers (Mw = 2000 and 5000) were studied as a model of multifunctional linear polymers in the reaction with L-tryptophan and GGYR. Alternative polymer-(multi)-peptide conjugates were successfully synthesized using Starburst dendrimer PAMAM (G = 3), 'short' and 'long'-chain PEG-based active esters and GRGDY. The structure of the intermediate precursors and peptide-conjugates was confirmed by spectral (UV-Vis, FTIR, H-NMR) and chromatographic (RP-HPLC and SEC) methods. By varying the properties of the interconnecting polymer--such as hydrophobicity, molecular weight, and functionality--a set of polymer-GRGDY conjugates was synthesized.

Cell Adhesion↗

PubMed1999

Nonionic polymers reverse inactivation of surfactant by meconium and other substances.

A variety of substances including human meconium have been found to affect adversely the surface tension-lowering activity of pulmonary surfactants, and this effect may be important in the pathogenesis of a number of human diseases. To find whether inactivation of surfactant could be prevented or reduced by nonionic polymers, we added dextrans, polyethylene glycols (PEGs), or polyvinylpyrrolidones (PVPs) of various molecular weights to pulmonary surfactants. One to 3% human meconium or other inactivating substances were then added to the mixtures, which were tested in a modified pulsating bubble surfactometer. Polymers (3.3-500 kD) in 1-10% concentrations enhanced the ability of a commercial surfactant replacement (Survanta) to lower the minimum surface tension in the presence of meconium, serum, or lysophosphatidylcholine. Similar effects were seen when polymers were added after mixing of surfactant and meconium or other inhibitors, indicating that polymers are capable of reversing the inactivation. Results from rat experiments indicate that total lung capacity is increased when PEG is first added to the Survanta, then mixed with meconium and instilled into the lungs. We postulate that polymers separate meconium-surfactant complexes, permitting surfactant components better access to the air-liquid interface. Taeusch HW, Lu KW, Goerke J, Clements JA. Nonionic polymers reverse inactivation of surfactant by meconium and other substances.

Animals↗

PubMed1991

An in vivo and in vitro study of the loss of plasticizer from soft polymer-gel materials.

Polymer-gel materials used as short-term denture soft linings are blended with plasticizers to lower the glass transition temperature (Tg). A lower Tg allows for greater polymer chain mobility, thus producing a more flexible material. The present work evaluated the loss of plasticizers due to leaching both in vivo and in vitro. Two commercial denture soft-lining materials (A and B) were tested. These were both poly(ethyl methacrylate) polymers, blended with alcohol and phthalate esters. A clinical study was conducted in which patients wore, sequentially, dentures bearing (on separate occasions) each of the two soft-polymer lining materials. The two materials A and B were randomly assigned for each of ten patients and were worn for 14 and 30 days, respectively. With one exception, patients wore dentures with both lining materials, for a total of 19 clinical evaluations. The plasticizer loss occurring during the clinical trial was determined by GC analysis from the initial and terminal day sampling of plasticizer content of the soft polymer-gel materials. The results of this analysis were compared with results obtained from an in vitro leachability study by use of sink conditions in water at 37 degrees C for the same two commercial soft polymers conducted over the same time periods of 14 and 30 days. The results indicated that a higher loss of plasticizer occurred in vivo, compared with the in vitro tests for 17 of the 19 clinical evaluations. The average plasticizer lost in vivo from material A at 14 days was 122 +/- 58 mg/g, and for material B at 30 days it was 33 +/- 27 mg/g.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylic Resins↗

PubMedDate not supplied

Osmotic load from glucose polymers.

Glucose polymer is a carbohydrate source with variable chain lengths of glucose units which may result in variable osmolality. The osmolality of two commercial glucose polymers was measured in reconstituted powder infant formulas, and the change in osmolality of infant milk formulas at the same increases in energy density (67 kcal/dL to 81 and 97 kcal/dL) from the use of additional milk powder or glucose polymers was compared. All samples were prepared from powders (to nearest 0.1 mg), and osmolality was measured by freezing point depression. For both glucose polymers the within-batch variability of the measured osmolality was less than 3.5%, and between-batch variability of the measured osmolality was less than 9.6%. The measured osmolality varies linearly with energy density (p less than 0.001) and was highest in infant formula reconstituted from milk powder alone. However, there exist significant differences in the measured osmolality between different glucose polymer preparations. At high energy densities (greater than or equal to 97 kcal/dL), infant milk formulas prepared with milk powder alone or with the addition of certain glucose polymer preparation may have high osmolality (greater than or equal to 450 mosm/kg) and theoretically predispose the infant to complications of hyperosmotic feeds.

Glucose↗

PubMedDate not supplied

The use of a biocompatible orthopaedic polymer in the treatment of loose total hip prostheses.

Seventeen cases of loose total hip prostheses were treated with biocompatible orthopaedic polymer, an osteoconductive co-polymer. Biocompatible orthopaedic polymer permits improved stability and secondary bone repair and may also act as a vehicle for adjunctive antibiotic therapy. The available forms of biocompatible orthopaedic polymer and their methods of application are described and the results obtained with their use are compared with the pre-operative clinical observations. Of the 17 patients studied, pain disappeared in 14, unlimited walking became possible in seven, while another eight patients were subsequently able to walk for over 300 m. Mobility became normal in 13 cases; full weight bearing on one leg became possible in 12 cases and became normal in another four. Radiological examination showed the development of a bony interface between the cortex and the prosthesis as the radiolucent biocompatible orthopaedic polymer material was converted into bone. It may, therefore, be concluded that, in this indication, biocompatible orthopaedic polymer appears to be an active interface for stabilizing loose total hip prostheses.

Adult↗

PubMed2001

New strategies for polymer development in pharmaceutical science--a short review.

We are developing synthetic polymers for pharmaceutical and medical applications. These applications can be broadly grouped on how the polymer will be utilized e.g. material, excipient or molecule. Our focus is to develop polymers with more defined structures that are based on biological, physicochemical and/or materials criteria. Strategies are being developed to more efficiently optimize structure-property correlations during preclinical development. We describe two examples of our research on pharmaceutical polymer development: narrow molecular weight distribution (MWD) homopolymeric precursors which can be functionalized to give families of narrow MWD homo- and co-polymers, and hydrolytically degradable polymers.

Drug Industry↗

PubMed1999

Crystallization of paracetamol from ethanol-water solutions in the presence of polymers.

We have examined the effect of polymer nature and concentration on yield and micromeritic, melting and compression properties of paracetamol crystals obtained from ethanol-water solutions using the solvent-change technique. Agar, gelatin, polyethylene-glycol (PEG) and polyvinylpyrrolidone (PVP) were the polymers used. These four polymers have different solubility in ethanol and water. It was found that the yield of crystallization may increase by up to 8% with agar, gelatin and PEG, polymers that are insoluble in ethanol, while the soluble PVP reduces yield by 14%. The size of crystals increased due to the addition of polymers and changed almost in parallel with the crystal yield for agar and gelatin. Gelatin resulted in the biggest crystals, agar in the most equidimensional (aspect ratio 1.45 and roundness 1.47) and PVP in the most elongated (aspect ratio 1.89 and roundness 2.13). PEG resulted in the most agglomerated crystals. Yield pressure, Py, decreased in the following order: agar > PEG > gelatin > PVP, which is the same order for the enthalpy of fusion. Gelatin and PEG significantly decreased the elastic recovery of tablets (0.05 level), probably due to plastic deformation of crystals and fragmentation of agglomerates, respectively. Crystallization of paracetamol in the presence of polymers by the solvent-change (ethanol-water) technique may permit increase of crystal yield, alteration of crystal shape and improvement of compression behaviour during tableting.

Acetaminophen↗

PubMed1994

Quantitative determination of the proportion of microtubule polymer present during the mitosis-interphase transition.

We have developed a new method for determining levels of tubulin polymer, based on quantitative fluorescence detection of x-rhodamine tubulin microinjected into living cells and we have applied this method to analysis of the mitosis-interphase transition. LLC-PK cells in interphase and mitosis were microinjected, then cooled and rewarmed to drive tubulin incorporation. Total tubulin fluorescence in individual, living cells was quantified using a cooled, scientific grade CCD image sensor. Cells were then washed and lysed into a microtubule-stabilizing buffer to extract the soluble pool. Total tubulin polymer fluorescence was determined for the extracted cells in the same way as for living cells. Fluorescence images were corrected by flat-fielding and background subtraction. The ratio of extracted cell fluorescence/living cell fluorescence for individual cells, was taken as the proportion of tubulin as polymer. Cells in M-phase, G1 and random interphase were analyzed. G1 cells had almost the same proportion as random interphase cells. Mitotic cells gave a value of 90 +/- 5% of G1 cells at 37 degrees C. Within M-phase, levels of tubulin as polymer in metaphase and early anaphase were not significantly different. In contrast to the general expectation of microtubule depolymerization at anaphase onset, these results indicate that as cells exit mitosis, the overall proportion of tubulin as polymer does not change dramatically even though the mitotic spindle disassembles. We conclude that the mitosis-interphase transition is accompanied by a redistribution of tubulin at an essentially constant polymer level. Therefore, a global shift to depolymerization conditions is not the driving force for anaphase chromosome movement.

Anaphase↗

PubMed1995

Release of lidocaine from polymer film dosage forms.

We investigated the in vitro drug release from mixed polymer films using lidocaine (LC), which is poorly water-soluble. The mixed polymer films consisted of various ratios of hydroxypropylcellulose (HPC) and hydroxypropylmethylcellulose phthalate (HPMCP). The effects of the presence glycyrrhizic acid (GL) or polyethylene glycol (PEG) in the films upon LC release were also studied. LC crystallinity decreased in the polymer film and this decrease was remarkable in the presence of GL, resulting in an amorphous state. During the initial stage, drug release was regarded as a zero-order dissolution. The apparent release rate constant, ka, varied with the ratios of the two polymers and the amount of additives as well as with the pH of the test solution. The results indicated that GL enhanced the dissolution rate of LC from mixed polymer films, which may be due to the formation of an amorphous state. On the other hand, since PEG is a surfactant, the enhanced wettability of the polymer by the buffered solutions may have caused the increased dissolution rate.

Calorimetry, Differential Scanning↗

PubMed1999

The removal of mercury from dental-operatory wastewater by polymer treatment.

The mercury (Hg) content of dental-operatory wastewater has become an issue in many localities, and Hg removal is rapidly becoming a matter of concern for all dental clinics. This preliminary study tested the efficacy of polymers for the removal of Hg contaminants from the dental-unit wastewater stream. Two commercially available polymers were used to treat dental-operatory wastewater. Used separately, each polymer removed from 74.9% to 88.4% of the Hg from dental-wastewater supernatant. The polymers used in combination, within the recommended pH range, removed up to 99.9% of the total Hg from dental-wastewater supernatant. The estimated optimal concentration of the two polymers is approximately 2.33 ml of each per liter of waste, and more than 90% of the Hg may be removed with 0.13 ml/l. Results indicate that a combination of the two polymers may sufficiently reduce Hg levels to allow discharge of clarified supernatants into public sewer systems.

Dentistry↗

PubMed2005

Mean-field model of immobilized enzymes embedded in a grafted polymer layer.

Two-dimensional mean-field lattice theory is used to model immobilization and stabilization of an enzyme on a hydrophobic surface using grafted polymers. Although the enzyme affords biofunctionality, the grafted polymers stabilize the enzyme and impart biocompatibility. The protein is modeled as a compact hydrophobic-polar polymer, designed to have a specific bulk conformation reproducing the catalytic cleft of natural enzymes. Three scenarios are modeled that have medical or industrial importance: 1), It is shown that short hydrophilic grafted polymers, such as polyethylene glycol, which are often used to provide biocompatibility, can also serve to protect a surface-immobilized enzyme from adsorption and denaturation on a hydrophobic surface. 2), Screening of the enzyme from the surface and nonspecific interactions with biomaterial in bulk solution requires a grafted layer composed of short hydrophilic polymers and long triblock copolymers. 3), Hydrophilic polymers grafted on a hydrophobic surface in contact with an organic solvent form a dense hydrophilic nanoenvironment near the surface that effectively shields and stabilizes the enzyme against both surface and solvent.

Adsorption↗

PubMed2003

Self-assembled DNA-conjugated polymer for novel DNA chip.

We developed DNA-conjugated polymer for DNA chip fabrication. A 30 mer probe DNA and disulfide bridges were covalently attached to the polymer side chain. The DNA-conjugated polymer can be specifically adsorbed on a gold substrate surface by a self-assembly technique. The interaction between fully matched DNA and DNA-conjugated polymer was investigated by surface plasmon resonance (SPR) technique. The DNA-conjugated polymer-modified gold surface highly recognized fully matched DNA, rather than unmatched DNA. Therefore, DNA-conjugated polymer can be used for novel DNA chip fabrication.

Base Sequence↗

PubMed2003

Preparation of uniformly sized molecularly imprinted polymers for phenolic compounds and their application to the assay of bisphenol A in river water.

Uniformly sized molecularly imprinted polymers, which can recognize bisphenol A (BPA), have been prepared by a multi-step swelling and polymerization method using BPA or a structurally related analogue of BPA [p-t-octylphenol (OP) or p-t-butylphenol (BP)] as the template molecule, 4-vinylpyridine as the functional monomer, and ethylene glycol dimethacrylate as the cross-linker. The BP-imprinted polymer showed higher molecular recognition ability for BPA than the OP-imprinted polymer. The BPA- and BP-imprinted polymers were applied for the assay of a trace amount of BPA in river water using column-switching HPLC with fluorescence detection: A BPA-imprinted polymer was used for removal of BPA from the pretreatment eluent as the trap column, and a BP-imprinted polymer was used for selective pretreatment and enrichment of BPA in river water as the pretreatment column. The calibration graph, constructed from peak area data plotted versus BPA concentration, was linear with a correlation coefficient of >0.999 in the concentration ranges of 25-1000 ppt. The limit of quantitation was 25 ppt with a 5-ml injection. The column-switching HPLC system was successfully applied for the assay of BPA in river water.

Benzhydryl Compounds↗

PubMed2005

High performance gene delivery polymeric vector: nano-structured cationic star polymers (star vectors).

Nano-structured hyperbranched cationic star polymers, called star vectors, were molecularly designed for a novel gene delivery non-viral vector. The linear and 3, 4 or 6 branched water-soluble cationic polymers, which had same molecular weight of ca. 18,000, were synthesized by iniferter (initiator-transfer agent-terminator)-based photo-living-radical polymerization of 3-(N,N-dimethylamino)propyl acrylamide, initiated from respective multi-dithiocarbamate-derivatized benzenes as an iniferter. All polymers produced polyion complexes 'polyplexes' by mixing with pDNA (pGL3-control plasmid), in which the particle size was ca. 250 nm in diameter [the charge ratio < 2/1 (vevtor/pDNA)] and ca. 150 nm (the charge ratio > 2.5/1), and the zeta-potential was ca. +10 mV (the charge ratio > 1/1). When COS-1 cells were incubated with the polyplexes 12 h after preparation under the charge ratio of 5/1, higher gene expression was obtained as an increase in branching, with a little cytotoxicity. The relative gene expression to the linear polymer was about 2, 5, and 10 times in 3-, 4-, and 6-branched polymers, respectively. The precise change in branching of polymers enabled the control of the gene transfer activity.

Animals↗

PubMed1998

Bead compacts. I. Effect of compression on maintenance of polymer coat integrity in multilayered bead formulations.

Little information is available on the compactability of beads for oral sustained-release dosage forms. It is known that polymer-coated beads may fuse together to produce a non-disintegrating controlled-release matrix tablet when compressed. This study evaluates the effect of compression on beads with multiple layers of polymer and drug coat, and the effect of cushioning excipients and compaction pressure on drug release from compressed bead formulations. The multilayered beads consist of several alternating layers of acetaminophen (APAP) and polymer coats (Aquacoat) with an outer layer of mannitol as a cushioning excipient. Percent drug release versus time profiles showed that the release of drug decreases from noncompacted beads as the amount and number of coatings increases, with only 43% of drug released in 24 hr for coated beads with 10 layers. It was shown that the compacted multilayered beads will disintegrate in gastrointestinal fluids, providing a useful drug release pattern. It was shown that beads of drug prepared by any method can be spray-layered with excipients such as Avicel and mannitol. Spray-layering of the cushioning excipient onto beads can provide an effective way to circumvent segregation issues associated with mixing of the polymer-coated beads and powdered or spherical/nonspherical cushioning excipients. Spray layering of the cushioning excipient can also provide excellent flow properties of the final formulation as visually observed in our experiments. Triple-layered caplets (TLC) were also prepared with outer layers of Avicel PH-101 or polyethylene oxide (PEO), and a center layer of polymer-coated beads. For TLC, the polymer coating on the beads fractured, and nondisintegrating matrix formulations were obtained with both caplet formulations.

Cellulose↗