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PubMedDate not supplied

Ultrasonic atomization and subsequent polymer desolvation for peptide and protein microencapsulation into biodegradable polyesters.

Peptide and protein microencapsulation into poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) microspheres continues to represent a technological challenge in terms of product sterility and up-scaling. The primary objective of this study was to examine the feasibility of a novel method for peptide and protein entrapment into PLA and PLGA microspheres, particularly suitable for up-scaling and aseptic processing. The method involves ultrasonic atomization of an organic polymer solution combined with subsequent organic solvent extraction by a hardening agent. The study evaluated the critical atomization conditions, the required molecular cohesion parameters of polymer solvents and hardening agent for particle preparation as well as the quality of entrapment and release as a function of polymer and peptide/protein type. Suitable polymer solvents and hardening agents were restricted to defined domains of fractional cohesion parameters: f(p) = 0.2-0.35 and f(h) = 0.2-0.4 for the polymer solvents, and f(p) = 0-0.1 and f(h) = 0-0.25 for the hardening agents. Microsphere size (0.1-100 micro m) was largely controlled by the viscosity of the atomized solution. Microencapsulation of the freely water-soluble bovine serum albumin and tetrapeptide thymocartin yielded modest efficiencies of 12-35%, whereas the slightly water-soluble octapeptide vapreotide pamoate was entrapped with 63-93% efficiency. Drug release was mainly governed by the polymer type, lasting over 100 days for BSA entrapped in PLA microspheres and; 20 days for vapreotide pamoate in PLGA 50 : 50 and for thymocartin in PLA. Very importantly, the novel method was readily accommodated within a laminar air-flow cabinet. Under aseptic conditions, sterile microspheres could be prepared. In conclusion, the novel method described may have potential in industrial environments.

Biocompatible Materials↗

PubMed2003

A review of microwave-assisted polymer chemistry (MAPC).

As a relatively new source of processing energy, microwave energy offers many compelling advantages in materials processing over conventional heat sources. These advantages include greater flexibility, greater speed and energy savings, improved product quality and properties, and synthesis of new materials that cannot be produced by other heating methods. Studies of microwave processing of polymeric materials in the early 1960s led to a successful industrial application in the rubber industry. Since the mid-1980's, there has been a great deal of interest in microwave processing of polymeric materials worldwide. The discipline can be categorized in two major fields: microwave-assisted polymer physics (MAPP) and microwave assisted polymer chemistry (MAPC). This paper offers an overview of the state-of-the-art research on the field of MAPC, including polymer processing (curing of thermosets, processing of thermoplastics, and joining), polymer synthesis, plasma modification of polymer surfaces, plasma polymerization, polymer degradation, and production of nanomaterials. Most of these studies have focused on laboratory-scale, exploratory efforts. Challenges and possible future directions for the commercialization of microwave processing technologies are discussed.

Biocompatible Materials↗

PubMedDate not supplied

Correlation between in vitro release and in vivo immune response from biodegradable polymer particles entrapping tetanus toxoid.

Release of immunoreactive antigen from biodegradable polymer particles in a manner mimicking the normal vaccination schedule is one of the most important requirements for the successful development of single dose vaccine formulation. Tetanus toxoid (TT) was used as a model antigen to develop single dose vaccine formulations using poly(lactide-co-glycolide) and poly(lactide)polymers. An amphiphilic stabilizer such as RSA or PVA was used at an optimal concentration in the internal aqueous phase during preparation of immunoreactive TT particles using the multiple emulsion solvent evaporation method. Particles made from different polymers released immunoreactive TT continuously for more than 4 months in vitro and release profiles were in accordance with the degradation characteristics of the polymer. Initial burst release of antigen from the particles was controlled by incorporation of different concentrations of PVA in the internal aqueous phase during particle formulation. The extent of antigen release from the particles was varied by changing the aqueous to organic phase volume during the primary emulsification stage of particles formulation. Use of above formulation variables resulted in the formulation of polymer particles having different in vitro release characteristics. Anti-TT antibody titers in vivo were also in accordance with the in vitro release characteristics of immunoreactive TT from the particles. Anti-TT antibody titers from the stabilized particles were much better than that observed from particles made without stabilizers. These results indicate the importance of stabilizers and different formulation variables for the preparation of polymer particles having desired in vitro release characteristics.

Animals↗

PubMed1998

The Correlation Between Symptoms, Frequent Use of Dental Polymers, and Evaluation of Health Risk.

Dental personnel are at risk as they manually handle polymer products containing monomers and additives that cause irritation and induce allergy. Gloves and face masks can be easily penetrated by monomers. A total of 587 dental personnel and a referent group (585) in the 2 most northern regions of Sweden were included in a questionnaire study (response rate 76%). Questions were asked regarding symptoms of atopy, asthma, conjunctivitis, atopic dermatitis, hand dermatitis, and hay fever/rhinitis. The dental personnel were asked to give the name of polymer products used in their practice and the frequency of use. They were also asked to risk evaluate 5 different types of polymer materials on a scale from 1 to 5. Analysis was done to find if the occurrence of a symptom was associated with a high risk evaluation of a polymer material, or with frequent use of a certain polymer product. Significantly more dentists reported symptoms of atopic dermatitis and conjunctivitis compared to referents and chair assistants. Results show that dental personnel with symptoms risk evaluated most materials significantly higher than dental personnel without symptoms. Further, the occurrence of some symptoms was associated with frequent use of 8 polymer products.

correlation analysis↗

PubMed2000

Basic coating polymers for the colon-specific drug delivery in inflammatory bowel disease.

During acute attacks of inflammatory bowel disease, the luminal pH of the colon decreases significantly. This drop in pH can be exploited by developing coated dosage forms with acid-soluble coating polymers to achieve topical drug delivery to the colon. Two batches of minitablets, a conventional and a swellable formulation, were prepared by direct compression and coated with different amounts of either Eudragit E or AEA in a small coating pan. The release of the model drug dexamethasone from the coated tablets was measured spectrophotometrically at pH 2.0, 4.0, 5.0, and 6.8 and different stirring rates (100-200 rpm) to simulate the influence of pH and hydrodynamic stress on drug release. In general, lag times of drug release, determined as the time points of a 5% drug release, were longer with AEA-coated cores compared to those coated with Eudragit E, resulting from a lower polymer dissolution rate and water permeability of this film. In low pH media, drug release was dependent on the stirring rate because the onset of drug release is determined by the time required for dissolution of the basic polymer films. At pH 6.8, lag times from nonswelling tablets coated with Eudragit E, for which drug release only begins after complete erosion of the polymer film, are not significantly affected by hydrodynamic stress. Drug release from AEA-coated cores is determined by the slow drug diffusion through the polymer film. Lag times from tablets with swelling properties, for which drug release is induced by disruption of the basic polymer films due to water penetration and subsequent core swelling, are not significantly affected by hydrodynamic stress. Additional coating layers such as an intermediate hydroxypropylcellulose (HPC) layer and an enteric outer layer do not influence the lag times of drug release, nor does a 2-hr pretreatment of the entire dosage form in acidic media.

Anti-Inflammatory Agents↗

PubMed1976

Stimulation of clonal growth of normal fibroblasts with substrata coated with basic polymers.

Improved media have reduced the amount of serum protein required for clonal growth of normal human and chicken fibroblast-like cells. In the presence of limiting amounts of serum protein, attachment of colonies to tissue culture plastic surfaces is weak. Treatment of the culture surface with polylysine or other basic polymers causes the cells to adhere much more tightly. Growth is also improved on the surfaces treated with basic polymers, and further reductions in the concentration of serum as possible. At sufficiently low protein concentrations, growth of some types of cells is totally dependent on the use of a treated surface. Several different types of normal human and chicken fibroblast-like cells show improved growth on polylysine-coated surfaces, but no improvement was obtained in growth of a line of SV-40 transformed WI-38 cells. Acidic and neutral polymers are generally inactive. Collagen and gelatin improve growth slightly, but the effect is much less than that obtained with basic polymers. Both natural and synthetic polymers with an excess of basic groups are active, including histone, polyarginine, polyhistidine, polylysine, polyornithine, and protamine. The only critical requirement appears to be a polymer that carries a positive charge at a physiological pH.

Blood Proteins↗

PubMed2001

Location of a constriction in the lumen of a transmembrane pore by targeted covalent attachment of polymer molecules.

Few methods exist for obtaining the internal dimensions of transmembrane pores for which 3-D structures are lacking or for showing that structures determined by crystallography reflect the internal dimensions of pores in lipid bilayers. Several approaches, involving polymer penetration and transport, have revealed limiting diameters for various pores. But, in general, these approaches do not indicate the locations of constrictions in the channel lumen. Here, we combine cysteine mutagenesis and chemical modification with sulfhydryl-reactive polymers to locate the constriction in the lumen of the staphylococcal alpha-hemolysin pore, a model protein of known structure. The rates of reaction of each of four polymeric reagents (MePEG-OPSS) of different masses towards individual single cysteine mutants, comprising a set with cysteines distributed over the length of the lumen of the pore, were determined by macroscopic current recording. The rates for the three larger polymers (1.8, 2.5, and 5.0 kD) were normalized with respect to the rates of reaction with a 1.0-kD polymer for each of the seven positions in the lumen. The rate of reaction of the 5.0-kD polymer dropped dramatically at the centrally located Cys-111 residue and positions distal to Cys-111, whether the reagent was applied from the trans or the cis side of the bilayer. This semi-quantitative analysis sufficed to demonstrate that a constriction is located at the midpoint of the pore lumen, as predicted by the crystal structure, and although the constriction allows a 2.5-kD polymer to pass, transport of a 5.0-kD molecule is greatly restricted. In addition, PEG chains gave greater reductions in pore conductance when covalently attached to the narrower regions of the lumen, permitting further definition of the interior of the pore. The procedures described here should be applicable to other pores and to related structures such as the vestibules of ion channels.

Animals↗

PubMed2002

Magnetization transfer imaging for polymer gel dosimetry.

Off-resonance RF pre-saturation was used to obtain contrast in MRI images of polymer gel dosimeters irradiated to doses up to 50 Gy. Two different polymer gel dosimeters composed of 2-hydroxyethyl-acrylate or methacrylic acid monomers mixed with N, N'-methylene-bisacrylamide (BIS), dispersed in an aqueous gelatin matrix were evaluated. Radiation-induced polymerization of the co-monomers generates a fast-relaxing insoluble polymer. Saturation of the polymer using off-resonance Gaussian RF pulses prior to a spin-echo readout with a short echo time leads to contrast that is dependent on the absorbed dose. This contrast is attributed to magnetization transfer (MT) between free water and the polymer, and direct saturation of water was found to be negligible under the prevailing experimental conditions. The usefulness of MT imaging was assessed by computing the dose resolution obtained with this technique. We found a low value of dose resolution over a wide range of doses could be obtained with a single experiment. This is an advantage over multiple spin echo (MSE) experiments using a single echo spacing where an optimal dose resolution is achieved over only very limited ranges of doses. The results suggest MT imaging protocols may be developed into a useful tool for polymer gel dosimetry.

Dose-Response Relationship, Radiation↗

PubMed2002

Synthetic thermoreversible polymers are compatible with osteoinductive activity of recombinant human bone morphogenetic protein 2.

Recombinant human bone morphogenetic protein 2 (rhBMP-2) is currently in clinical studies as part of an implantable device that contains a biomaterial carrier. Implant retention of rhBMP-2 by the biomaterial carrier is important for the osteoinductive activity. To control in situ retention of rhBMP-2, thermoreversible polymers were synthesized and characterized, and their compatibility with rhBMP-2-induced osteoinduction was investigated. The results indicated that polymers with a controlled "solubility <--> insolubility" transition temperature could be prepared from N-isopropylacrylamide, ethylmethacrylate, and N-acryloxysuccinimide (NASI). NASI-containing polymers were able to conjugate to rhBMP-2 without additional cross-linkers. Implantation in the rat ectopic model, where alkaline phosphatase and calcium deposition were utilized as markers of osteoinductive activity, indicated that rhBMP-2 mixed with the polymers were effective for osteoinduction. Moreover, rhBMP-2 conjugated to the chosen polymers was as effective as native rhBMP-2 in inducing ALP activity and calcium deposition. We conclude that thermoreversible polymers are compatible with rhBMP-2-induced osteogenesis and can serve as novel biomaterials for rhBMP-2 delivery.

Alkaline Phosphatase↗

PubMed2003

Preparation of degradable porous structures based on 1,3-trimethylene carbonate and D,L-lactide (co)polymers for heart tissue engineering.

Biodegradable porous scaffolds for heart tissue engineering were prepared from amorphous elastomeric (co)polymers of 1,3-trimethylene carbonate (TMC) and D,L-lactide (DLLA). Leaching of salt from compression-molded polymer-salt composites allowed the preparation of highly porous structures in a reproducible fashion. By adjusting the salt particle size and the polymer-to-particle weight ratio in the polymer-salt composite preparation the pore size and porosity of the scaffolds could be precisely controlled. The thermal properties of the polymers used for scaffold preparation had a strong effect on the morphology, mechanical properties and dimensional stability of the scaffolds under physiological conditions. Interconnected highly porous structures (porosity, 94%; average pore size, 100 microm) based on a TMC-DLLA copolymer (19:81, mol%) had suitable mechanical properties and displayed adequate cell-material interactions to serve as scaffolds for cardiac cells. This copolymer is noncytotoxic and allows the adhesion and proliferation of cardiomyocytes. During incubation in phosphate-buffered saline at 37 degrees C, these scaffolds were dimensionally stable and the number average molecular weight (Mn) of the polymer decreased gradually from 2.0 x 10(5) to 0.3 x 10(5) in a period up to 4 months. The first signs of mass loss (5%) were detected after 4 months of incubation. The degradation behavior of the porous structures was similar to that of nonporous films with similar composition and can be described by autocatalyzed bulk hydrolysis.

Biocompatible Materials↗

PubMed1986

Dietary regulation of intestinal glucohydrolases in adult rats: comparison of the effect of solid and liquid diets containing glucose polymers, starch, or sucrose.

For 1 wk, 3-mo-old male rats were fed a low-starch (5 cal%), high-fat (73 cal%, corn oil) diet followed by a high-glucose-polymer (70 cal%), low-fat (7 cal%, corn oil) or a middle-glucose-polymer (40 cal%), middle-fat (37 cal%, corn oil) diet. Other animals were fed similar diets but with starch or sucrose instead of the glucose polymers. Rats were sacrificed 2 or 7 days later. Food intake, body weight changes, and protein content per intestinal segment were similar in all groups. Increased carbohydrate intake evoked an increase of sucrase, maltase, glucoamylase, and lactase activity in both the jejunum and ileum. Effect of glucose polymers on glucohydrolase was similar in animals fed commercial liquid-soy-based infant formulas containing sucrose, glucose polymers, or both. Results support using glucose polymers as replacements for sucrose or starch when digestion impairment of those sugars is suspected or when a formula of lower osmolality is indicated.

Animals↗

PubMed1986

Glucose polymer increases jejunal calcium, magnesium, and zinc absorption in humans.

The present study investigated the effect of glucose polymer on jejunal calcium, magnesium, and zinc absorption in eight normal subjects, using the triple-lumen intestinal perfusion technique. For each subject, a 30-cm segment of jejunum was perfused for 60 min each with two different test solutions. When 4 mM glucose polymer was perfused net calcium absorption increased by fourfold (95 vs 488 mumol/30 cm/h), and net jejunal uptake of magnesium (393 mumol/30 cm/h) was observed, as compared to net magnesium secretion in the absence of glucose polymer. In addition, coadministration of glucose polymer doubled net zinc absorption (13 vs 29 mumol/30 cm/h). The rate of water absorption increased from 49 to 111 ml/30 cm/h. No further change in jejunal water and mineral absorption was observed when glucose polymer in the perfusate was increased from 4 to 8 mM. These results suggest that glucose polymer may have potential as an agent to significantly enhance mineral absorption.

Adult↗

PubMed1987

Effects of glucose and glucose polymers on calcium absorption in healthy subjects.

Glucose polymers have been shown to enhance intestinal calcium absorption in normal subjects as well as in patients with gastrointestinal disease. Glucose polymers are widely used as an energy source in enteral nutritional supplements and infant formulas. In this study, eight normal subjects underwent 47Ca absorption tests to compare the effect on calcium absorption of carbohydrate given orally as a simple carbohydrate (glucose) or a more complex carbohydrate (glucose polymers). Oral coadministration of glucose with calcium increased the efficiency of intestinal calcium absorption by 20% and coadministration of glucose with glucose polymers increased calcium absorption by 27%. This suggests that glucose, derived from glucose polymers by hydrolysis, may be responsible for the positive effect of polymers on calcium absorption. The potential positive effect of coadministration of carbohydrate on calcium bioavailability deserves considerations in the design of calcium supplementation strategies.

Adult↗

PubMed1994

Binding of teicoplanin and vancomycin to polymer surfaces.

Both teicoplanin and vancomycin were found to bind to a range of polymer surfaces. The binding of teicoplanin to specimen vessel surfaces was, on average, four times greater than that of vancomycin and was particularly marked with silconized polymers (5.2 micrograms/cm2). Pre-exposure of a polymer surface to human body fluids caused a 60% reduction in teicoplanin binding. Reduction of the negative surface charge on a polymer surface with ferric nitrate resulted in a ten-fold increase in teicoplanin binding. The accumulation of a strain of Staphylococcus epidermidis on silicone rubber catheter segments pre-exposed to glycopeptide antibiotics was examined. In phosphate buffered saline binding of bacteria to vancomycin-treated polymer was greater than to an unexposed control surface. In contrast, in human serum both antibiotics caused reductions in adherent growth. The binding of glycopeptide antibiotics, in particular teicoplanin, to polymer surfaces may interfere with the results of in-vitro assays. However, this phenomenon may be useful in the prevention of bacterial accumulation on the surfaces of medical devices.

Bacterial Adhesion↗

PubMed1985

Evaluation of a peritoneal dialysis solution containing polymer.

Glucose is used in peritoneal dialysate to produce the gradient for ultrafiltration. The peritoneal membrane's low reflection coefficient for glucose imposes a demand for high transmembrane concentrations, perhaps adding unwanted body burden of glucose. A polymer with a lower permeation rate used as an osmotic agent would circumvent this. We evaluated the mass transfer coefficient (mtc), T1/2 disappearance from the peritoneal cavity and ultrafiltration capabilities of a 900 dalton (Mn) starch derived polymer. We compared an 8% (455 mOsm/L) and a 10% (484 mOsm/L) polymer (Pol) solution to available dialysate solutions containing 2.5% (399 mOsm/L) and 4.25% (491 mOsm/L) X glucose (Glc). The dialysate compositions were otherwise similar. Using a randomized complete block design, 5 anephric dogs maintained on chronic peritoneal dialysis were studied. The mtc (ml/min) was greater for the glucose than the polymer solutions (p less than 0.05): 2.5%-13 and 4.25%-14 vs 8%-5 and 10%-6. The T1/2 disappearance (min) was also greater (p less than 0.05): 2.5% Glc-112 and 4.25% Glc-111 vs 8% Pol-281 and 10% Pol-252. Over a 180 min. period the 2.5% glucose solution generated the least volume of ultrafiltrate (ml, p less than 0.05): 2.5% Glc-113 and 4.25% Glc-589 vs 8% Pol-640; 10% Pol-912. We conclude that the lower permeation rate of the polymer yields ultrafiltration at a lower dialysate osmolality. A polymer solution may be a feasible alternative to glucose.

Animals↗

PubMed2005

Evaluation of cisplatin and a novel platinum polymer conjugate for drug toxicity and drug distribution in mice.

The toxicity and distribution of cisplatin and two novel platinum (Pt) polymer conjugates (Pt-6 and Pt-7) were determined in serum and tissue of BALB/c mice at specific time points after i.p. administration of a drug bolus containing identical Pt concentrations. Pt concentrations were determined in serum, liver and kidney at 5 and 15 min, respectively, after drug administration by inductively coupled plasma mass spectrometry. It was found that the Pt polymer Pt-7 gave rise to a considerably lower Pt concentration in serum and considerably higher concentration in liver and kidney than cisplatin. LD25 measurements indicated that the Pt-7 polymer is considerably less toxic than cisplatin. In vitro experiments and determination of IC50 values in a variety of human tumor cell lines, normal lymphocytes and fibroblasts confirmed that Pt-6 and Pt-7 polymers are 40-500 times more toxic for tumor cells than for normal cells, perhaps reflecting preferential uptake. The toxicity of cisplatin was found to be only 1.6-40 times more effective in tumor cells. These inter-relationships are supported by the observation that the tumor enrichment factor (TEF) for cisplatin is only in the region of 6, and much lower than for Pt-6 and Pt-7, where TEFs are in the region of 40 and 150, respectively. These results demonstrate that the Pt polymer conjugates exhibit greater tumor specificity than cisplatin, killing tumor cells more effectively while being considerably less toxic for normal cells. It is concluded that the Pt polymer conjugates may be superior for cancer therapy and warrant further testing to assess their full clinical potential.

Animals↗

PubMedDate not supplied

Inhibition of bacterial adhesion and biofilm formation by a heparinized hydrophilic polymer.

The adhesion and growth of two pathogenic bacteria (Escherichia coli and Staphylococcus aureus) on the surface of a heparinized hydrophilic polymer were studied. Heparinized hydrophilic polymer is composed of poly(vinyl chloride) grafted with poly(ethylene glycol) monomethacrylate, diethylaminoethyl methacrylate, and ionically bound heparin. Poly(vinyl chloride) was used as a control. Plasma protein pre coated polymers were also prepared to evaluate the effect of proteins on bacterial adhesion. Polymer films were stored in bacterial suspensions under gentle shaking at 37 degrees C for 24 hr. The amount of adherent bacterial cells was measured by the bioluminescent assay of bacterial adenosine triphosphate. Their structure was observed by use of a scanning electron microscope. These evaluations demonstrated that a large amount of bacterial adhesion and biofilm formation was found on the surface of poly(vinyl chloride), whereas significant reductions in bacterial adhesion and no biofilm formation were observed on heparinized hydrophilic polymer. Bacterial adhesion onto plasma protein pre coat polymer films were also investigated, and it was clear that the bacterial adhesion on these surfaces was dependent upon the amount and species of absorbed proteins.

Adsorption↗

PubMed2001

Inhomogeneous model colloid-polymer mixtures: adsorption at a hard wall.

We study the equilibrium properties of inhomogeneous model colloid-polymer mixtures. By integrating out the degrees of freedom of the ideal polymer coils, we derive a formal expression for the effective one-component Hamiltonian of the (hard sphere) colloids that is valid for arbitrary external potentials acting on both the colloids and the polymers. We show how one can recover information about the distribution of polymer in the mixture given knowledge of the colloid correlation functions calculated using the effective one-component Hamiltonian. This result is then used to furnish the connection between the free-volume and perturbation theory approaches to determining the bulk phase equilibria. For the special case of a planar hard wall the effective Hamiltonian takes an explicit form, consisting of zero-, one-, and two-body, but no higher-body, contributions provided the size ratio q=sigma(p)/sigma(c)<0.1547, where sigma(c) and sigma(p) denote the diameters of colloid and polymer respectively. We employ a simple density functional theory to calculate colloid density profiles from this effective Hamiltonian for q=0.1. The resulting profiles are found to agree well with those from Monte Carlo simulations for the same Hamiltonian. Adding very small amounts of polymer gives rise to strong depletion effects at the hard wall which lead to pronounced enhancement of the colloid density profile (close to the wall) over what is found for hard spheres at a hard wall.

Adsorption↗