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PubMed2004

[The advance in researches for biomedical intelligent polymer materials].

The properties of biomedical intelligent polymer materials can be changed obviously when there is a little physical or chemical change in external condition. They are in the forms of solids, solutions and polymers on the surface of carrier, including aqueous solution of hydrophilic polymers, cross-linking hydrophilic polymers (i.e. hydrogels) and the polymers on the surface of carrier. In this paper are reviewed the progress in researches and the application of biomedical intelligent polymer materials.

Biocompatible Materials↗

PubMed2004

Surfactants, polymers and their nanoparticles for personal care applications.

A "touch me not" plant folding up rapidly upon being attacked or microbes depositing on teeth or ocean vessels even under hostile conditions are examples in nature that provide inspiration for developing new classes of personal care release or deposition systems. In this paper, development of such systems based on polymer/surfactant colloid chemistry is explored for achieving transport and release of cosmetic and pharmaceutical molecules at desired rates at desired sites. The successful development of products depends upon understanding and utilizing key interactions among surfactants, polymers and hybrid polymers that are relevant to personal care products. Thus, the absorbed layers or tethers on the particulates can be manipulated for desired dispersion of actives or depositions on substrate under any and all conditions. New hybrid polymers and nanogels have been synthesized for tuning up nanodomains that can extract and deliver at will cosmetics/drugs/toxins by perturbing pH, temperature or ionic strength of the system. Particularly, hydrophobically modified polymers have features of both polymers and surfactants and due to the associative nature of the hydrophobic groups, such polymers can form intramolecular nanodomains for performing carrier functions. Nanogels developed recently include that of polyacrylamide, poly(acrylic acid) and starch nanogels modified for extraction and subsequent slow release of fragrances and overdosed toxic drugs. Binding and release processes were investigated using surface plasmon resonance and fluorescence spectroscopies, powerful techniques for monitoring short term and long term changes.

Cosmetics↗

PubMedDate not supplied

Crystallization of a non-steroidal anti-inflammatory drug from ethanol-water solution in presence of polymers: physicochemical characterization and release behaviour from suppositories.

Altered crystallization condition has been designed and adopted to a model non-steroidal anti-inflammatory drug, while crystallizing from ethanol-water solution in absence and presence of polymers such as Eudragit RS and ethylcellulose. To minimize the gastro-intestinal side effects nimesulide was considered as a model drug candidate for the development of suppository formulation. Physicochemical characteristics of the crystals were evaluated by Scanning Electron Microscopy (SEM). X-ray diffraction (XRD) and Fourier Transformed Infrared Spectroscopy (FT-IR). Smoothness and sharpness of the crystal have been decreased with increased concentration of a polymer. A little change in crystal habit and geometry has also been observed. Crystals are discrete in nature and more than 90% were in the range of 20-90 micron. The X-ray diffractions of nimesulide crystallized in absence of polymer and physical mixture of drug-polymer revealed fewer high intensity reflections when compared with the drug crystallized in presence of Eudragit RS, which testified a slight decreased ordering of crystal lattice in the latter. In presence of ethylcellulose, slightly increased ordering of crystal lattice was observed. No strong interactions were noticed as revealed by FT-IR spectroscopy. Drug dissolution rate from suppository formulations containing nimesulide crystallized in presence of polymer was found to delay as compared with the suppository prepared by nimesulide crystallized in absence of polymer.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

Toxic vessel reaction to an absorbable polymer-based paclitaxel-eluting stent in pig coronary arteries.

OBJECTIVES: The goal of this study was to evaluate a new drug-eluting stent (DES) comprising a bioabsorbable polymer eluting a moderate dose of paclitaxel in a clinically relevant animal model. BACKGROUND: Although DES limit restenosis, adverse vascular pathologies and toxicities continue to be of major concern. Optimization of DES components, especially completely absorbable polymers, may reduce these toxicities. METHODS: Bare-metal (BM), absorbable polymer coating only (POLY), and polymer-based paclitaxel-eluting (PACL) stents were implanted in porcine coronary arteries using intravascular ultrasound (IVUS) to optimize stent apposition. The dose density of paclitaxel was 0.30-0.35 mcg/mm2, with in vitro elution studies demonstrating a gradual elution over 6-8 weeks. The animals were terminated at 1 week, 1 month and 3 months. Histopathologic and histomorphometric analyses were perform. RESULTS: The arteries with PACL showed extensive smooth muscle cell necrosis at 1 week and poor apposition of stent struts at 1 month (malapposition measured as gap width between strut and internal elastic lamina), with greater gap width compared to the BM and POLY groups (0.22 mm +/- 0.02 vs. 0.03 mm +/- 0.02 and 0.02 mm +/- 0.01, respectively; p < 0.001). At 3 months, the PACL group showed rebound neointimal thickness and histological percent stenosis compared to the BM group (0.48 mm +/- 0.14 vs. 0.07 mm +/- 0.02, respectively; p < 0.001 and 59% +/- 11 vs. 17% +/- 2, respectively; p < 0.001). CONCLUSIONS: Despite in vitro data showing slow, sustained release of paclitaxel from a bioabsorbable polymer, the porcine coronary artery model demonstrated a sequence of medial necrosis, stent malapposition and late neointimal thickening. Since the therapeutic window for paclitaxel may be narrower than currently inferred, thorough preclinical testing coupled with the polymer development process for stents eluting paclitaxel is needed.

Absorbable Implants↗

PubMed2006

Review of the use of polymers in saliva substitutes for symptomatic relief of xerostomia.

It is clear from the many clinical studies carried out on currently available saliva substitutes, that the main factors limiting the success of polymers in treating xerostomia is their short duration of action and/or their lack of acceptability by users. The most effective formulations for severe sufferers of xerostomia contain relatively viscous, thixotropic polymers, which mild to moderate sufferers in particular tend to dislike. Relief can also be extended by increasing concentrations of non-thixotropic polymers; however, this also has to be balanced by the decrease in palatability resulting from higher polymer levels. In addition, gels rather than solutions tend to result from higher polymer concentrations, which are only employed by the most severe sufferers of xerostomia, and in fact, have been suggested to offer little improvement in efficacy over oral sprays. It would be highly advantageous to improve the duration of relief without impacting negatively on the sensory profile of the product. This would provide a longer lasting effect that is acceptable to all sufferers of xerostomia. The essential role of polymers in saliva substitutes is to provide lubrication, hydration, and protection of the oral mucosa, providing symptomatic relief to sufferers of xerostomia. However, saliva substitutes should also be of neutral or near neutral pH, to prevent demineralization of the oral hard tissues. These products should always be used in conjunction with a thorough oral health regimen, but may also contain appropriate levels of electrolytes for remineralization of enamel and dentine.

Animals↗

PubMed1991

The antibody-linked chelating polymers for nuclear therapy and diagnostics.

This review deals with the problem of protein modification with chelating polymers. The main purpose of this approach is the preparation of monoclonal antibodies labeled with heavy metal isotopes (alpha-, beta-, and delta-emitting metals and metals used for NMR-tomography). Traditional binding of metals with proteins via chelating agents directly coupled to protein molecule does not allow binding a high number of metal atoms per single protein molecule and can also alter protein specific properties. At the same time, metal-to-protein binding via intermediate chelating polymer makes possible the binding of several dozen metal atoms per single protein without affecting its specific properties. Moreover, the variations in polymer properties and molecular weight allow controlled modified antibody biodistribution and clearance rate. Modified antibodies can be used successfully for nuclear and NMR diagnostics and for nuclear therapy. The following problems are discussed: the chemistry of the coupling of chelating groups to polymer backbone; the binding of chelating polymers to proteins, including monoclonal antibodies; the ability of chelating polymer-to-protein conjugates to bind heavy metals; the influence of the modification on protein conformation and specific properties; the behavior of metal-containing conjugates in vivo; the practical use of conjugates obtained for radioimmunoimaging, radioimmunotherapy, NMR-tomography, and in vitro immunoassays. Future prospects of the approach are also discussed.

Antibodies, Monoclonal↗

PubMed1990

Levodopa delivery from controlled-release polymer matrix: delivery of more than 600 days in vitro and 225 days of elevated plasma levels after subcutaneous implantation in rats.

Parkinson's disease is commonly treated with orally applied levodopa (l-dopa). However, because this treatment modality is associated with a number of undesirable side effects, some due to plasma fluctuations, we have developed a slow-release polymer system that can be used to deliver l-dopa continuously for extended periods of time in vitro (greater than 600 days) and in vivo (at least 225 days) in rats. In vitro l-dopa release was evaluated using polymer matrices with appropriately selected parameters (loading and geometry), and zero-order (linear) release of l-dopa was observed for more than 600 days (in highly loaded, noncoated material first-order kinetics), in some instances in mg quantities per day. This was achieved even in polymer matrices, which did not possess a dissolution limiting barrier. Scanning electron-microscopic analysis suggests that the mechanism of release is dissolution through channels and pores within the polymer matrix. To assess in vivo release, l-dopa was quantified in plasma from rats given s.c. implants of l-dopa polymer matrices using high-performance liquid chromatography. We observed release of l-dopa for a period of at least 225 days after an initial burst of release. Continuous release of l-dopa from s.c. implanted slow-release polymer matrices has several advantages over oral delivery: 1) l-dopa plasma fluctuations are eliminated, 2) patient compliance issues are reduced and 3) the gastrointestinal tract is circumvented, thus requiring a lower dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

[Structure-release relationship of physical polymer/drug combinations. 2. Diffusion of 3-methylpyrazole through a synthetic polymer matrix].

The diffusion of 3-methylpyrazole through a synthetic polymer matrix and the effect of the solubility of the bioactive agent in polymers on the release behaviour of polymer combinations were studied. With increasing hydrophilicity of the polymer both the diffusion and the diffusion coefficient of 3-methylpyrazole increased and the solubility of the agent in the polymer decreased. The hydrophilicity of various polymers is discussed on the basis of a parameter determined by turbidimetric titrations.

Chemical Phenomena↗

PubMed1985

Biological effects of soluble synthetic polymers as drug carriers.

Soluble synthetic polymers have already, with limited success, found some use medically as plasma expanders and as polymeric drugs. Currently, many other potential biomedical applications are under evaluation, including the use of soluble polymers as targetable drug carriers, as carriers of immunogenic compounds, and as bioadhesives. In order to exploit their undoubted clinical potential to the fullest, it is obviously essential to understand the inter-relationship between synthetic polymers and their biological environment. The biological effects of soluble synthetic polymers to be covered include their immunogenicity, the therapeutic potential of polymeric drugs, and polymer-drug conjugates and their biocompatibility. These active responses are discussed in relation to the differential fates of different soluble polymers in the body.

Animals↗

PubMed1985

[Structure-release relationships of active polymeric drug combinations. 1. The influence of polymer structure on the diffusion of 3-methylpyrazole from monolithic systems].

The release of 3-methylpyrazole from monolithic polymer films into aqueous media has been studied. The diffusion of the active agent decreased with increasing of the content of acetate groups in reacetylated poly(vinyl alcohols) and with increasing of the ester lengths in copolymers of maleic esters, respectively. The release rate of active ingredient is dependent on the hydrophilicity of the polymer films. Contrary to the glass transition temperature the hydrophilicity of polymers expressed the interaction between polymer chains and water in a direct way. The hydrophilicity of copolymers of maleic esters correlated with the turbidimetric point, which can be determined by acidimetric titrations. The influences of interactions between polymers and the active agents on their diffusion in the polymers were also discussed.

Chemical Phenomena↗

PubMed1984

Biodegradable polymers in controlled drug delivery.

Erosion mechanisms are divided into three types and drug release within each type is described. Type I erosion involves hydrolysis of hydrogels and these are useful in the controlled release of macromolecules entangled within their network structure. Type II erosion involves solubilization of water-insoluble polymers by reactions involving groups pendant from the polymer backbone. Of particular interest are polymers that solubilize by ionization of carboxylic acid groups, and the utilization of those systems is described. Type III erosion involves cleavage of hydrolytically labile bonds within the polymer backbone and four distinct polymer systems within this category are under development. One system involves the diffusion of drugs from a reservoir through a bioerodible membrane, another system utilizes microcapsules, a third system utilizes monolithic devices, and the fourth system utilizes drugs chemically bound to a bioerodible polymer.

Acetals↗

PubMed1993

Characterization of the transglutaminase-mediated large molecular weight polymer from rat liver; its relationship to apoptosis.

A large molecular weight sodium dodecyl sulfate (SDS)-insoluble polymer was isolated from rat liver and shown to be a product of transglutaminase activity by virtue of its high epsilon(gamma glutamyl)lysine content. Antiserum raised against this polymer crossreacted with another product of transglutaminase activity, the apoptotic envelope isolated from cultured hamster fibrosarcoma cells. The amino acid composition of isolated apoptotic envelopes and the SDS-insoluble polymer were found to be comparable, although not identical. Using the polymer antiserum, the apoptotic index (mg polymer protein per mg DNA) of normal and tumor tissue was determined and found to correlate with the associated transglutaminase activity. Localization of proteins involved in polymer formation in neonatal rat liver cells was found immunohistochemically to be in those cells undergoing apoptosis; these cells also stained selectively for transglutaminase. Several proteins from liver homogenate were found to crossreact with the antipolymer serum, notably proteins of 120, 80, 43 and 38 kDa.

Animals↗

PubMedDate not supplied

Evaluation of a polymer implanted port access device.

UNLABELLED: The implanted port vascular access system has provided many patients with safe and reliable vascular access. Its implanted design provides improved body image, reduced maintenance and a better quality of life. The Huber needle has been the standard means of accessing the implanted port system. Because of the problems associated with the Huber needle system, current standards recommend that the Huber needle be changed every 7 days. This evaluation examines the use of a polymer cannula to access the implanted port system. This polymer cannula eliminates many of the problems associated with the Huber needle and provides longer dwell times without increased complications. Seventy nine patients were accessed for a total of 1533 days with the mean dwell time being 19.4 days with no increase in complications associated with port access. OBJECTIVE: To establish implanted port access times of greater than 7 days without increased complications. DESIGN: A multicenter voluntary enrollment evaluation of a medical device. PATIENTS: Patients were offered the opportunity to participate in the evaluation if they had an implanted port and were going to be accessed for therapy for periods of 7 days or more. MEASUREMENTS: Patients were observed for adverse cutaneous reactions at the insertion site and any port access complications such as sepsis, leakage, changes in portal chamber integrity, and implant pocket integrity. RESULTS: From October 1994 through November 1995, 79 L-Cath for Ports (Luther Medical Products) polymer catheter port access devices (Illustration 1) were inserted in 54 patients. This polymer port access device was used instead of a rigid metal Huber needle for port access. The total number of access days was 1533 days with the mean duration of access being 19.4 days. Two patients experienced blood stream infections while they were accessed with the polymer port access device. These infections ensued with fever of unknown origin as the presenting symptom during neutropenic episodes after chemotherapy treatment. The port access device was removed and the port access device tip was cultured with culture results being negative. No other patients experienced complications related to the port access device. CONCLUSION: The polymer port access device provided a safe and effective means of extending port access times. This reduced the number of restarts for the patients and could extend portal septum life by exposing the portal septum to fewer accesses.

Catheters, Indwelling↗

PubMed1997

Anionic polymers in cell walls of gram-positive bacteria.

Information on the prevalence, compositions, and structures of anionic carbohydrate-containing polymers of cell walls of Gram-positive bacteria is summarized. The data suggest that these polymers are important for normal functioning of bacterial cells and require further studies. Structural data on teichoic acids found in the literature published over the last few years are discussed. This is a very diverse class of polymers whose structure-specific pathways of degradation were studied and NMR spectra were examined. Unique comprehensive tables of 13C-NMR spectroscopic data (mainly obtained by the authors) on these polymers are given in the Appendix. Other tables summarize data on teichuronic acids, sugar-phosphate polymers, acid polysaccharides, and structural variants of bonds between acid polysaccharides and peptidoglycans known from the literature. Functions of anionic polymers and their possible chemotaxonomic applications are discussed.

Anions↗

PubMed1998

Increasing the cyclodextrin complexation of drugs and drug biovailability through addition of water-soluble polymers.

For a variety of reasons, including cost, production capabilities and toxicology, the amounts of cyclodextrin (CD) that can be included in drug formulations is limited and, thus, it is important to develop methods which can be applied to enhance the complexation efficacy. Moreover, bioavailability of drugs in CD containing vehicles can be rather limited resulting in less than optimal drug delivery. Addition of small amounts of a water-soluble polymer to the aqueous complexation media enhances the CD complexation of drugs. Thus, less CD is needed to dissolve a given amount of drug when a polymer is present than when it is not present in the aqueous complexation media. Furthermore, the bioavailability of drugs is enhanced through addition of polymers. In general, the water-soluble polymers improve both pharmaceutical and biological properties of drug-CD complexes. This polymer enhancement of drug complexation and bioavailability is independent of the physiochemical properties of the drug. Thermodynamic studies and other physicochemical observations indicate that the polymers participate directly in the drug-CD complexation.

Animals↗

PubMed1998

Biocompatibility, cell adhesion, and degradation of surface-modified biodegradable polymers designed for the upper urinary tract.

OBJECTIVES: The aim of this study was to develop a short bioresorbable ureteric stent and to characterize polymers and their surface modifications with respect to biocompatibility, degradation kinetics, cell adhesion properties, and incorporation of biologically active substances. Poly(D,L-lactide) PDLLA, poly(D,L-lactide-co-glycolide) PDLLA-co-GLY, and poly(D,L-lactide-co-trimethylenecarbonate) PDLLA-co-TMC were chosen as basic polymers. Surface modification was performed by plasma-induced graft polymerization and included grafting with hydroxyethylmethacrylate (HEMA), oligo(ethyleneoxide)-monomethacrylate (OEOMA), and acrylic acid (AAC). Biocompatibility of the polymers was assessed in vitro applying parameters of cell morphology, proliferative activity, and cell adhesion. All polymers were biocompatible and exerted no toxic effect on urothelial cell lines and on primary human urothelial cell cultures. A markedly reduced cell adhesion could be achieved in polymers grafted with HEMA, OEOMA, and AAC. Our results indicate that surface modification of bioresorbable polymers by grafting with HEMA, OEOMA, or AAC is an efficient approach to improve surface properties with respect to biocompatibility and cell adhesion properties.

Absorption↗

PubMed1996

Preparation and characterization of high-surface-area polymer substrates for microcalorimetry.

The preparation and characterization of high-surface-area polymeric substrates suitable for the microcalorimetry of protein adsorption are described. High-surface-area polystyrene, poly(styrene-co-butyl methacrylate) and poly(styrene-co-allyl alcohol) were prepared by adsorbing polymer from solution onto fumed silica. Verification of adsorption of polystyrene by silica was determined by noting peak shifts of the surface silanol group in the infrared. The amount of polymer adsorbed was determined from adsorption isotherms. The minimum thickness of polystyrene required to mask silicon oxide properties was found to be that thickness at which contact angles became constant, about 35 A. Polymer densities were measured. Water contact angles on each polymer surface indicate that poly(styrene-co-allyl alcohol) has the surface most wettable by water. Polymer-water interfacial energies were estimated from pendant drop results and a harmonic mean equation along with contact angles. Two methods were used to estimate the polar and dispersion components of the three polymers. Both methods predicted polystyrene to have the highest interfacial energy against water, and one method predicted poly(styrene-co-allyl alcohol) to have the lowest. A Wilhelmy plate study verified the change in interfacial properties as a function of contact time with water. A study of the heats of adsorption of lysozyme by each substrate using a modified Tien-Calvet microcalorimeter demonstrated the suitability of the substrates for microcalorimetry.

Adsorption↗

PubMed1997

The differential effects of poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate)/poly(caprolactone) polymers on cell proliferation and collagen synthesis by human lung fibroblasts.

Because of its chemical versatility and demonstrated biocompatibility, poly(2-hydroxyethyl methacrylate) (pHEMA) has been widely used as a polymer for biomedical applications. Since this hydrophilic material shows a poor interface with cells, blendings with other polymers were done to improve cytocompatibility. In our polymer, the presence of hydrophobic dominions on the material surface, due to the interpenetrating polymerization of pHEMA with poly(caprolactone) (PCL), seems to ameliorate the cytocompatibility in terms of cell adhesion and metabolism. For our experiments, we used IMR-90 human fibroblasts, as these cells strongly regulate DNA, RNA, and protein synthesis as anchorage-dependent variables. Cell attachment on a pHEMA/PCL interpenetrating polymer network was optimal, suggesting a strong adhesion between the cells and the polymer surface. Cell adhesion was weaker on pHEMA, as a significant fraction of the fibroblasts revealed a lack of spreading, with most cells remaining spherical. Moreover, only fibroblasts seeded on pHEMA significantly decreased mRNA synthesis; collagen production and cell shapes ranged from fully flat and proliferating, to minimally spread and nonproliferating. Finally, DNA synthesis, as a measure of cell proliferation, was markedly inhibited in cells cultured on pHEMA but not on pHEMA/PCL. In conclusion, our results suggest that control of cell growth and metabolism by biomedical polymers is based on physicochemical mechanism(s) in which the hydrophilicity/hydrophobicity ratio of the material surfaces may play an important role.

Base Sequence↗