Article

Water state effect on drug release from an antibiotic loaded polyurethane matrix containing albumin nanoparticles

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Abstract

Water mobility plays a crucial role in determining transport properties of small molecules in polymer matrices. In particular, in drug delivery systems, water state affects the pharmacokinetics, especially drug absorption, diffusion and release. In the present study, the state of water in an antibiotic-loaded composite consisting of albumin nanoparticles (BSA(np)) dispersed into a carboxylated polyurethane (PEUA) has been investigated and compared with that of the single drug-loaded components. The antibiotic cefamandole nafate was used as a model drug. DSC analysis, used to evaluate the freezing and non-freezing water fractions in the hydrated samples, showed that in BSA(np) water can adsorb both in the inter-particles regions and inside the particles. With increasing of total adsorbed water amount, the contribution of the freezing water fraction was higher than the non-freezing one. As for PEUA, the majority of water molecules absorbed is in a mobile freezing state (about 60% of the W(tot)). As for the PEUA/BSA(np) composite, the higher polyurethane phase segregation induced by the nanoparticles as well as the higher non-freezing water fraction significantly enhanced drug uptake with respect to PEUA. Moreover, the greater non-freezing water fraction allowed the drug to penetrate within BSA nanoparticles and to give rise then to a controlled drug release. Indeed, the diffusion barrier exerted by nanoparticles and the matrix prolonged the antimicrobial activity from 4 to 9 days. Finally, the higher polyurethane phase segregation also improved composite mechanical properties, as evidenced in stress-strain experiments and dynamic mechanical analysis.

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... They help in maintaining the required drug concentration levels within the body without undergoing rapid clearance. Recent studies (Averineni et al., 2012;Avgoustakis et al., 2002;Gryparis et al., 2007;Hammady et al., 2009;Martinelli et al., 2011;Morgen et al., 2012;Rescignano et al., 2012;Sant et al., 2005;Sawyer et al., 2011;Soppimath et al., 2001;Valot et al., 2010) have revolved around the use of biocompatible and biodegradable polymeric nanoparticles that serve as carriers transporting drugs to the site of action. These nanoparticles are usually synthesised by dispersing a polymer in an organic solvent followed by transfer into a non-solvent, or by direct polymerisation of monomers. ...
... These authors pointed out that the pore structure could have an important implication on drug release kinetics but did not relate structural evolution to release profile. DSC has also been used to study the drug release behaviour from albumin nanoparticles contained within a carboxylated polyurethane matrix (Martinelli et al., 2011). An investigation of the water freezing and melting, water uptake and drug release kinetics was used to purportedly determine the two main factors that contributed to controlled drug release mechanisms. ...
... An investigation of the water freezing and melting, water uptake and drug release kinetics was used to purportedly determine the two main factors that contributed to controlled drug release mechanisms. Firstly, Martinelli et al. (Martinelli et al., 2011) reported burst release was due to a swelling mechanism, while controlled release was due to a diffusion dependent mechanism. They attributed the above two mechanisms to the presence of freezing and nonfreezing fractions which aided the presence of a dual diffusion barrier that prolonged the drug release in their materials (Martinelli et al., 2011). ...
Article
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PLGA/PLA polymeric nanoparticles could potentially enhance the effectiveness of convective delivery of drugs, such as carboplatin, to the brain, by enabling a more sustained dosage over a longer time than otherwise possible. However, the link between the controlled release nanoparticle synthesis route, and the subsequent drug release profile obtained, is not well-understood, which hinders design of synthesis routes and availability of suitable nanoparticles. In particular, despite pore structure evolution often forming a key aspect of past theories of the physical mechanism by which a particular drug release profile is obtained, these theories have not been independently tested and validated against pore structural information. Such validation is required for intelligent synthesis design, and NMR cryoporometry can supply the requisite information. Unlike conventional pore characterisation techniques, NMR cryoporometry permits the investigation of porous particles in the wet state. NMR cryoporometry has thus enabled the detailed study of the evolving, nanoscale structure of nanoparticles during drug release, and thus related pore structure to drug release profile in a way not done previously for nanoparticles. Nanoparticles with different types of carboplatin drug release profiles were compared, including burst release, and various forms of delayed release. ESEM and TEM images of these nanoparticles also provided supporting data showing the rapid initial evolution of some nanoparticles. Different stages, within a complex, varying drug release profile, were found to be associated with particular types of changes in the nanostructure which could be distinguished by NMR. For a core-coat nanoparticle formulation, the development of smaller nanopores, following an extended induction period with no structural change, was associated with the onset of substantial drug release. This information could be used to independently validate the rationale for a particular synthesis method. Hence, the specific reasons for the effectiveness of the synthesis route, for obtaining core-coat nanoparticles with delayed release, have been elucidated.
... Chen et al. explored the use of polyurethane pressure-sensitive adhesives for transdermal drug delivery [6]. Several studies have explored the controlled release of antibiotics from polyurethane matrices through tissue scaffolds [7], bone grafts [8], microspheres [9] and nanoparticles [10]. Temperature-and pH-responsive polyurethane nanoparticles have been developed to deliver doxorubicin to the tumor microenvironment [11]. ...
... Pharmaceutics 2018,10,55 ...
Article
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Since their introduction over 50 years ago, polyurethanes have been applied to nearly every industry. This review describes applications of polyurethanes to the development of modified release drug delivery. Although drug delivery research leveraging polyurethanes has been ongoing for decades, there has been renewed and substantial interest in the field in recent years. The chemistry of polyurethanes and the mechanisms of drug release from sustained release dosage forms are briefly reviewed. Studies to assess the impact of intrinsic drug properties on release from polyurethane-based formulations are considered. The impact of hydrophilic water swelling polyurethanes on drug diffusivity and release rate is discussed. The role of pore formers in modulating drug release rate is examined. Finally, the value of assessing mechanical properties of the dosage form and approaches taken in the literature are described.
... Polyurethane matrices Cefamandole nafate Carboxylated polyurethane/antibiotic-loaded albumin nanoparticles composite Exhibited controlled drug release [27] Prolonged antimicrobial activity from 4 to 9 days 5 Nanostructured polyurethane matrix Cefamandole nafate Bovine serum albumin or polyallylamine nanoparticles loaded with antibiotic incorporated in a polyurethane matrix [28] Prolonged antimicrobial activity up to 9 days. 6 Temperature-and pHresponsive PU-based nanoparticles Doxorubicin Hexamethylene diisocyanate (HDI) and 4,4′-diphenylmethane diisocyanate (MDI)-based PUs showed temperatureand pH-responsive properties [29] Efficient encapsulation into polyurethane nanoparticles and uptaken by Huh-7 cells HDI-based PUs were nontoxic 7 Polyurethane foams DB-67 and doxorubicin Covalent incorporation of anticancer compounds DB-67 and doxorubicin into polyurethane foam [30] Rates were dependent on temperature and chemical structure of the drug Differential release of covalently bound drugs 8 ...
... Incorporation of albumin nanoparticles into the carboxylated PU matrix system was explored for improvement in drug absorption due to greater surface/volume ratio and enhancement in drug release rates. Cefamandole nafate was loaded into the above nanostructured composite system from which long-term release of drug was observed [27]. Iodine, a strong disinfectant, was loaded into PU matrix, which was investigated as coating material for hospital equipment during the manufacture process. ...
Chapter
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Polyurethanes (PUs) are synthesized by reaction of diisocyanates with polyols, resulting in the formation of repeatable units of carbamate (urethane) linkages. They are often coupled with other diols or diamines (chain extenders) to fine-tune their mechanical properties. PUs are used in day-to-day household items, for heavy engineering, in sophisticated instruments, and also in biomedical research. This chapter reviews the applications of PUs in the context of drug delivery. The chapter is classified on the basis of different delivery systems that may be fabricated from PUs such as nanoparticle systems, shape-memory system, stimulus-responsive system, and covalently conjugated systems. PUs have been around for more than 75 years, and still have a lot to offer to meet the demands of newer systems.
... Figure 6.10 shows the drug release profile of gentamicin sulfate in PU composites containing different types of nanoparticles. Albumin nanoparticle composites release drug at a faster rate in comparison to pure PU [123]. Similarly, CNT-based hyperbranched PU composites also exhibit slower release compared to pure PU and the release rate decreases with increasing amounts of CNTs in the matrix [124]. ...
... 10 Sustained drug release profile of polyurethane composites with different types of nanoparticles. (a) In the presence of albumin nanoparticles[123], (b) in CNTs[124], the number indicates the percentage of CNT, and (c) in the presence of clay[125]. ...
Chapter
This chapter describes the influence of different type of nanoparticles such as metals and metals oxides, ceramics, natural clay, various forms of carbon and zeolites on the properties of polyurethanes with special emphasis on the dimensionality of the nanoparticles. First, classification of the nanoparticles is made with typical examples. Distribution of the particles in polyurethane matrix and their interaction with the polymer chain alters the morphology of polyurethane both at the surface as well as in the bulk which in turn responsible for the dramatic changes in the properties of the composites. Organic modification on the surface of the nanoparticles make significant changes to the overall properties of the composites. Self-assembly phenomena in polyurethanes are illustrated where hydrogen bonded molecular layers stack together forming bigger clusters observable in optical microscope. The impact of layer by layer self-assembly on drug delivery and other properties are discussed. Improvement in the thermal, mechanical properties and flame retardancy of the composites with different type of nanoparticles are presented in detail with suitable examples. Polyurethanes are widely used in biomedical fields and the present chapter elaborates the effectiveness of the composites towards biocompatibility including in-vivo use vis-à-vis pure polyurethanes. It is suggested that polyurethane nanocomposites have great potential in biomedical applications.
... The use of silver nanoparticles (NPs) is now considered as one of the most promising strategies to combat biofilm infections related to indwelling medical devices (Gong et al., 2007). Drug delivery nanocarriers systems, such as liposomes (Tamilvanan et al., 2008) and polymer-based (Martinelli et al., 2011) carriers have also arisen as appealing methods with a great potential in the treatment of biofilm infections, due to several factors especially good biocompatibility and ample range and extent of drugs that they can carry. Another important factor is the protection provided by the encapsulation of the drug in the biological milieu, decreasing toxicity and allowing the drug to reach the specific site. ...
... Recently, Crisante et al. (2009) developed a nanostructured polymer system for antibiotic delivery using bovine serum albumin or polyallylamine as pore forming substances. Their results were corroborated by the work of Martinelli et al. (2011), who hypothesize that this system possesses the suitable features for the manufacturing of different types of antimicrobial medical devices, including intravascular catheters. However, studies in vivo are still required to test the efficacy of this antibiotic delivery carrier system. ...
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Nanoscience and Nanotechnology (N&N) are new approaches to research phenomena at atomic, molecular and macromolecular scales, where properties differ significantly from those at a larger scale. This new approach can be applied to microbial biofilms, which are formed when bacterial and/or yeast cells adhere to abiotic and biotic surfaces. It is well known that microorganisms in biofilms have a different behaviour from their planktonic counterparts, demonstrating a general recalcitrance to medical therapy. Therefore, biofilm-associated infections on indwelling medical devices, such as catheters and prostheses, may persist even after suspension of antibiotic therapy and hence may require the removal of the device. In order to reducepatiens morbidity and mortality, as well as high economical costs associated to medical biofilms, several attempts have been made to develop novel mechanisms of biofilm prevention and/or elimination. In this mini-review, the current knowledge on the features of biofilm formation and their relevance to medical device-associated infections are enclosed, as well as the new anti-biofilm approaches based on nanotechnology.
... For biofunctionalization, the antibioticloaded composite mixed with the albumin nanoparticles were used. 68,69 Chlorhexidine-releasing coatings: The chlorhexidine is recognized as the most effective antiseptic against a wide variety of gram-positive and gram-negative bacterial species. Chlorhexidine is bacteriostatic at low concentrations whereas shows bactericidal activity at higher concentrations. ...
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The implants are increasingly being a part of modern medicine in various surgical procedures for functional or cosmetic purposes. The progressive use of implants is associated with increased infectious complications and prevention of such infections always remains precedence in the clinical settings. The preventive approaches include the systemic administration of antimicrobial agents before and after the surgical procedures as well as the local application of antibiotics. The relevant literature and existing clinical practices have highlighted the role of antimicrobial coating approaches in the prevention of implants associated infections, although the applications of these strategies are not yet standardized, and the clinical efficacy is not much clear. The adequate data from the randomized control trials is challenging because of the unavailability of a large sample size although it is compulsory in this context to assess the clinical efficacy of preemptive practices. This review compares the efficacy of preventive approaches and the prospects of antimicrobialcoated implants in preventing implant-related infections.
... For biofunctionalization, the antibioticloaded composite mixed with the albumin nanoparticles were used. 68,69 Chlorhexidine-releasing coatings: The chlorhexidine is recognized as the most effective antiseptic against a wide variety of gram-positive and gram-negative bacterial species. Chlorhexidine is bacteriostatic at low concentrations whereas shows bactericidal activity at higher concentrations. ...
Article
Full-text available
The implants are increasingly being a part of modern medicine in various surgical procedures for functional or cosmetic purposes. The progressive use of implants is associated with increased infectious complications and prevention of such infections always remains precedence in the clinical settings. The preventive approaches include the systemic administration of antimicrobial agents before and after the surgical procedures as well as the local application of antibiotics. The relevant literature and existing clinical practices have highlighted the role of antimicrobial coating approaches in the prevention of implants associated infections, although the applications of these strategies are not yet standardized, and the clinical efficacy is not much clear. The adequate data from the randomized control trials is challenging because of the unavailability of a large sample size although it is compulsory in this context to assess the clinical efficacy of preemptive practices. This review compares the efficacy of preventive approaches and the prospects of antimicrobial-coated implants in preventing implant-related infections.
... Предложено немало способов решения проблемы адгезии бактериальной биопленки к медицинским изделиям. Один из наиболее очевидных способов -введение антибиотика -описан в [12], а в [13] изучены антибактериальные свойства по отношению к S. aureus композитных полиуретановых волокон, содержащих антибиотик ципрофлоксацин. ...
... Porous PU membranes as nonerodible drug-eluting stents (91), PU-based stent coatings enabling adjustable drug release (92), and pressure-sensitive PU adhesives for transdermal drug delivery (93) have been constructed so far. PUs have also been explored as matrices for the controlled release of antibiotics through tissue scaffolds (94), bone grafts (95), microspheres (96), and nanoparticles (97). PU nanocomposites that are responsive to the stimuli of temperature and pH have been developed to deliver doxorubicin to tumor microenvironments (98). ...
Chapter
Increasing attention to hygiene and health care has led to the development of biomedical and biomedical material applications. Various biomedical applications have been created from polymers due to their swift development. Polyurethanes (PUs) have several important biomedical applications. The most advanced biomedical applications—including responses to stimuli, drug delivery, scaffolding, prosthesis development, and wound dressing—have determined the importance of PUs and PU nanocomposites. Also, preparation of smart and responsive PUs can improve their biomedical applications. The next generation of PU biomedical applications belongs to smart, benign, biocompatible, and durable PUs, with appropriate physicochemical properties.
... A plethora of different polymer systems has been designed to prevent or treat biofilm formation, including: (i) cationic polymers [11,12]; (ii) antibacterial peptide-mimetic polymers [13,14]; (iii) polymers or composites able to load and release bioactive molecules [15][16][17]; and (iv) antifouling polymers, able to repel microbes by physical or chemical mechanisms [18]. The potential fields of application of antimicrobial polymers are numerous. ...
Article
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The rapid increase in the emergence of antibiotic-resistant bacterial strains combined with a dwindling rate of discovery of novel antibiotic molecules has lately created an alarming issue worldwide [...]
... The drug release from polyurethane was observed to be 8.6% higher and extended for a period of 19 days [83]. Martenelli et al. [84] prepared carboxylated polyurethane consisting of albumin nanoparticles. An antibiotic drug (cefamandole nafate) was loaded into the nanoparticles. ...
... Controlled drug release from nondegradable polymer systems occurs through a diffusion mechanism [16][17][18], while degradable polyesters, such as PLLA and PHB, with unstable chemical bonds, can be affected by hydrolytic reactions, specifically through the mechanism of end group autocatalysis [19]. In this connection, despite the impressive technological achievements in the creation of ultrathin fibers, an extremely limited amount of work [20][21][22] has been devoted to diffusion and hydrolytic problems that emerge in fibrillar materials during drug delivery. ...
... surfaces and produce extracellular substances that facilitate adhesion and provide a structural matrix, forming multicellular communities the biofilms. [7] Drug delivery nanocarriers systems, such as liposomes [8] and polymer-based [9] carriers have also arisen as appealing methods with a great potential in the treatment of biofilm infections, due to several factors especially good biocompatibility and ample range and extent of drugs that they can carry. ...
Article
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Antibacterial agents are very important in the textile industry, water disinfection, medicine, and food packaging. Organic compounds used for disinfection have some disadvantages, including toxicity to the human body; therefore, the interest in inorganic disinfectants such as metal oxide nanoparticles (NPs) is increasing. This review focuses on the Preparation and their potential with good antimicrobial activity of Ag-NPs and Se-NPs against biofilm forming S. aureus. Such improved antibacterial agents locally destroy bacteria, without being toxic to the surrounding tissue. We also provide an overview of opportunities and risks of using NPs as antibacterial agents. In particular, we discuss the role of Ag-NPs and Se-NPs materials. Several manufactured nanoparticles-particles with one dimension less than 100 nm are increasingly used in consumer products. At nano size range, the properties of materials differ substantially from bulk materials of the same composition, mostly due to the increased specific surface area and reactivity, which may lead to increased bioavailability and toxicity. Thus, for the assessment of sustainability of nanotechnologies, methods of manufacturing Nanoparticles, properties have to be studied. The formation of nanoparticle and physiochemical parameters such as pH, monomer concentration, ionic strength as well as surface charge, particle size and molecular weight are important for drug delivery. Further, these nanoparticles have the capability to reverse multidrug resistance a major problem in chemotherapy. Well-established therapies commonly employed in cancer treatment include surgery, Chemotherapy, immunotherapy, and radiotherapy. The silver nanoparticles might be involved in neutralizing these adhesive substances, thus preventing biofilm formation. Selenium is also one of essential trace elements in the human body and has great importance in nourishment and medicine. Medical Poonam World Journal of Pharmacy and Pharmaceutical Sciences diagnostic field also developed to use the selenium nanoparticles and also studies on the increase efficiency of glutathione peroxidase and thioredosin reductase.
... Controlled drug release from nondegradable polymer systems occurs through a diffusion mechanism [16][17][18], while degradable polyesters, such as PLLA and PHB, with unstable chemical bonds, can be affected by hydrolytic reactions, specifically through the mechanism of end group autocatalysis [19]. In this connection, despite the impressive technological achievements in the creation of ultrathin fibers, an extremely limited amount of work [20][21][22] has been devoted to diffusion and hydrolytic problems that emerge in fibrillar materials during drug delivery. ...
Article
Full-text available
Fibers of poly(L-lactic acid) (PLLA)/polyhydroxybutyrate (PHB) with different concentrations of the drug dipyridamole (DPD) were prepared using solvent-free melt electrospinning to obtain a polymeric drug delivery system. The electrospun fibers were morphologically, structurally, thermally, and dynamically characterized. Crazes that resemble lotus root crevices were interestingly observed in the 7:3 PLLA/PHB fibers with 1% DPD. The crystallinity of PLLA slightly decreased as PHB was incorporated, and the addition of DPD significantly reduced the melting temperature of the composite. The interactions between PLLA and PHB mainly occurred at a proportion of 7:3, and drug encapsulation in the fibers was verified. The kinetic profiles of drug release demonstrated the predominant multiple patterns involving a diffusional stage in the short-term mode of release and kinetic process related to the hydrolysis of the biopolymers. Furthermore, the dynamic behavior of the polymer molecules was evaluated based on the segmental mobility using probe electron spin resonance spectroscopy. The segmental mobility in the amorphous fraction of PLLA decreased with increasing PLLA content. The 9:1 PLLA/PHB system was more resistant to polymer hydrolysis than to the 7:3 system and the rate of diffusion transport was approximately two times higher for the 7:3 PLLA/PHB fibers than for the 9:1 PLLA/PHB fibers.
... In these systems, the establishment of drug/polymer ionic interactions controlled the loading extent and release rate with a consequent antibiofilm ability up to 7 days, as shown by SEM micrographs of PU surfaces untreated or treated with tigecycline (Fig. 3). A control of drug release was also achieved by incorporating antibioticloaded NPs in PU coatings (59,60). ...
Article
The use of implantable medical devices is a common and indispensable part of medical care for both diagnostic and therapeutic purposes. However, as side effect, the implant of medical devices quite often leads to the occurrence of difficult-to-treat infections, as a consequence of the colonization of their abiotic surfaces by biofilm-growing microorganisms increasingly resistant to antimicrobial therapies. A promising strategy to combat device-related infections is based on anti-infective biomaterials that either repel microbes, so they cannot attach to the device surfaces, or kill them in the surrounding areas. In general, such biomaterials are characterized by antifouling coatings, exhibiting low adhesion or even repellent properties towards microorganisms, or antimicrobial coatings, able to kill microbes approaching the surface. In this light, the present overview will address the development in the last two decades of antifouling and antimicrobial biomaterials designed to potentially limit the initial stages of microbial adhesion, as well as the microbial growth and biofilm formation on medical device surfaces.
... The antibiotic-loaded system consisted of a carboxylated polyurethane (PEUA) containing bovine serum albumin nanoparticles (BSAnp) which act as drug reservoir. In order to better understand the PEUA/BSAnp composite drug release properties and the mechanical behaviour, a detailed physical investigation on the material and on its interaction with absorbed water was carried out (Martinelli et al., 2011). ...
... Hence, nanosized organic and inorganic particles are finding increasing attention in medical applications due to their amenability to biological functionalization. Based on enhanced effectiveness, the new age drugs re-nanoparticles of polymers, metals or ceramics, which can combat conditions like cancer and fight human pathogens like bacteria[3].Silver nanoparticles (Ag-np) are among the most commercialised nanoparticles due to their antimicrobial potential[4].Production of silver nanoparticles can be achieved through different methods[5].Silver nanometal has been used in many consumer applications, mostly because of its recognized inhibitory effect towards many bacterial strains & micro organisms commonly present in medical & industrial process.Production of nanoparticles can be achieved through different methods. Chemical approaches are the most popular methods for the production.However, some chemical methods cannot avoid the use of toxic chemicals in the synthesis protocol[6].Since, noble metal nanoparticles such as silver, gold nanoparticles are widely applied to human contacting areas, there is a growing need to develop environmentally friendly processes of nanoparticles synthesis that do not use toxic chemicals(.Biological systems such as microorganisms and plants have a unique ability to control the structure phase and nano structural topography of the inorganic crystals[7,8].Use of plants for the fabrication of nanoparticles has drawn attention of researchers as a rapid, low cost, eco friendly and a single step method for the biosynthesis of nanoparticles for the first time demonstrated synthesis of gold nanoparticles inside a live plants[9,10]. ...
Article
The plants Asparagus adscendens, Bacopa monnieri, Ocimum bacilicum, and Withania somnifera were used and compared for their extracellular synthesis of metallic copper nanoparticles (CuNPs). Stable Cu nanoparticles were formed by treating aqueous solution of CuSO4•5H2O with the plant leaf extracts as reducing agent. By treatment of 1mM aqueous solutions of CuSO4•5H2O with leaf extract stable CuNPs were formed; the change in color of solution confirm the formation of stable nanoparticles. UV-Visible study revealed qualitative formation of CuNPs and characteristic absorption peak in Asparagus adscendens, Bacopa monnieri and Ocimum bacilicum leaf extract at the range of 500-700nm but in Withania somnifera leaf extract absorption peak of CuNPs is shifted at the range of 500-800nm. These biosynthesized CuNPs were characterized with the help of Fourier transform infrared spectroscopy (FTIR), and Transmission Electron Microscopy (TEM). The involvement of primary and secondary metabolites or possible reducing agent confirmed by FTIR analysis. TEM confirms the formation and the crystalline nature of Copper nanomaterial. This method can be used as effective and environmental friendly technique for the synthesis of Copper nanoparticles using leaf extract of different plants. The antibacterial potentials of the CuNPs were studied and these are shown good antimicrobial activity against Gram positive and Gram negative bacteria.
... Hence, nanosized organic and inorganic particles are finding increasing attention in medical applications due to their amenability to biological functionalization. Based on enhanced effectiveness, the new age drugs re-nanoparticles of polymers, metals or ceramics, which can combat conditions like cancer and fight human pathogens like bacteria [3].Silver nanoparticles (Ag-np) are among the most commercialised nanoparticles due to their antimicrobial potential [4].Production of silver nanoparticles can be achieved through different methods [5].Silver nanometal has been used in many consumer applications, mostly because of its recognized inhibitory effect towards many bacterial strains & micro organisms commonly present in medical & industrial process.Production of nanoparticles can be achieved through different methods. Chemical approaches are the most popular methods for the production.However, some chemical methods cannot avoid the use of toxic chemicals in the synthesis protocol [6].Since, noble metal nanoparticles such as silver, gold nanoparticles are widely applied to human contacting areas, there is a growing need to develop environmentally friendly processes of nanoparticles synthesis that do not use toxic chemicals(.Biological systems such as microorganisms and plants have a unique ability to control the structure phase and nano structural topography of the inorganic crystals [7,8].Use of plants for the fabrication of nanoparticles has drawn attention of researchers as a rapid, low cost, eco friendly and a single step method for the biosynthesis of nanoparticles for the first time demonstrated synthesis of gold nanoparticles inside a live plants [9,10]. ...
Article
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Objective: Synthesis of silver nanoparticles from callus extract of Justicia jendaracia (Burm.f) and the anti bacterial activity,ecotoxicity of the synthesized particles has been studied in the present study. Methods: The callus was induced in Murashige and Skoog (MS) medium supplemented with growth regulators and evaluated for nanoparticles synthesis. Anti bacterial activity was studied against human pathogenic bacteria Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 29213) was done by well diffusion assay.Ecotoxicity study was studied against Vigna mungo under pot assay. Results: The extract from the callus showed ability of synthesis of nanoparticles with plasmon absorption maxima at 430 nm, spherical particles with the size range of 50–65 nm. The antibacterial activity with these synthesized nanoparticles showed distinct effect on the all the tested strains. Ecotoxicity study reveals that nanoparticles did not cause any distinct effect on soil macronutrients, soil enzyme activity, soil microbial population and plant growth parameters of Vigna mungo. Conclusion. Present study would suggest possible utilization of biogenic silver nanoparticles from the callus extract of Justicia jendaracia as the therapeutic agent without causing any undesirable effects to the environment.
... 65 This system possesses features that are potentially amenable to the manufacture of antimicrobial medical devices, including IVCs. 68 However, in vivo studies are yet to be performed, to test the efficacy of this antibiotic delivery carrier system in reducing bacterial colonization and biofilm formation on catheters. ...
Article
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Intravascular catheter-related infections are still a major problem in health care and are associated with significant morbidity, mortality, and additional cost. The formation of microbial biofilm on catheters makes these infections particularly complicated, as microbial cells that detach from the biofilm can lead to infection, and because these microorganisms are highly resistant to many antimicrobial agents; thus, catheter removal is often required to successfully treat infection. To reduce the risks of catheter-related infections, many strategies have been applied, such as improvements in aseptic insertion and post-insertion care practices, implantation techniques, and antibiotic coated or impregnated materials. However, despite significant advances in using these methods, it has not been possible to completely eradicate biofilm infections. Currently, nanotechnology approaches seem to be among the most promising for preventing biofilm formation and resultant catheter-related bloodstream infection (especially with multi-resistant bacterial strains). In this review, current knowledge about catheter technology and design, the mechanisms of catheter-related bloodstream infection, and the insertion and care practices performed by medical staff, are discussed, along with novel, achievable approaches to infection prevention, based on nanotechnology.
... Different interactions between drug and urethane segments (hydrophobic, polar/charge, Hbonding) were found to retard the drug release rates (Sharma et al., 1988). In a carboxylated PU matrix made of MDI, PPO and dihydroxymethyl-propionic acid (as a chain extender), an antibiotic drug (cefamandole nafate; CEF) was loaded through adsorption (Martinelli et al., 2011). The PU matrix also contained dispersed albumin nanoparticles and a high drug loading was obtained, most likely due to hydrophobic interaction between the drug and protein. ...
... Earlier studies stated that water mobility has a critical role in transport properties of molecules in polymers. Particularly in drug delivery systems, water state can affect drug pharmacokinetics (absorption, diffusion, release, etc.) (25,26). As reported by Farkas et al., water solubility (% w/v) of CDG is much higher than the one of CDA, >70.0 and 1.8, respectively (27). ...
Article
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The widespread use of indwelling medical devices has enormously increased the interest in materials incorporating antibiotics and antimicrobial agents as a means to prevent dangerous device-related infections. Recently, chlorhexidine-loaded polyurethane has been proposed as a material suitable for the production of devices which are able to resist microbial contamination. The aim of the present study was to characterize the in vitro release of chlorhexidine from new polymeric orthodontic chains realized with polyurethane loaded with two different chlorhexidine salts: chlorhexidine diacetate or chlorhexidine digluconate. The orthodontic chains constituted of three layers: a middle polyurethane layer loaded with chlorhexidine salt inserted between two layers of unloaded polymer. In vitro release of chlorhexidine diacetate and digluconate from orthodontic chains loaded with 10% or 20% (w/w) chlorhexidine salt was sustained for 42 days and followed Fickian diffusion. The drug diffusion through the polyurethane was found to be dependent not only on chlorhexidine loading, but also on the type of chlorhexidine salt. The antibacterial activity of 0.2% (w/w) chlorhexidine diacetate-loaded orthodontic chain was successfully tested towards clinically isolated biofilm forming ica-positive Staphylococcus epidermidis via agar diffusion test. In conclusion, the chlorhexidine salt-loaded chains could provide an innovative approach in the prevention of oral infections related to the use of orthodontic devices.
... The TFV solubility in hydrated HPEU 20 pellets (ω s ) was determined to be 0.020 ± 0.003% (w/w) (N = 5, mean ± SD); considerably less than the 0.1% (w/w) obtained by scaling TFV solubility by aqueous mass fraction. This suggests that TFV has limited solubility in the polymer phase of this HPEU, and furthermore supports that only a fraction of water molecules in the hydrated HPEU are free to solubilize TFV [34]. Porosity-adjusted TFV solubility values (ω s ⁎ ) were calculated for each IVR batch using Eq. ...
Article
In vitro testing and quantitative analysis of a matrix, hydrophilic polyether urethane (HPEU) intravaginal ring (IVR) for sustained delivery of the anti-HIV agent tenofovir (TFV) are described. To aid in device design, we employed a pseudo-steady-state diffusion model to describe drug release, as well as an elastic mechanical model for ring compression to predict mechanical properties. TFV-HPEU IVRs of varying sizes and drug loadings were fabricated by hot-melt extrusion and injection molding. In vitro release rates of TFV were measured at 37°C and pH 4.2 for 30 or 90days, during which times IVR mechanical properties and swelling kinetics were monitored. Experimental data for drug release and mechanical properties were compared to model predictions. IVRs loaded with 21% TFV (w/w) released greater than 2mg TFV per day for 90days. The diffusion model predicted 90day release data by extrapolating forward from the first 7days of data. Mechanical properties of IVRs were similar to NuvaRing®, although the matrix elastic modulus decreased up to three-fold following hydration. This is the first vaginal dosage form to provide sustained delivery of milligram quantities of TFV for 90days. Drug release and mechanical properties were approximated by analytical models, which may prove useful for the continuing development of IVRs for HIV prevention or other women's health indications.
... More recently, Crisante et al. (2009) developed nanostructured polymer systems for antibiotic delivery using bovine serum albumin or polyallylamine as pore forming substances. Their results were corroborated by the work of Martinelli et al. (2011), which hypothesize that this system possesses suitable features for the manufacture of different types of antimicrobial medical devices, including intravascular catheters. ...
Article
Full-text available
Central venous catheters (CVCs) nowadays constitute critical devices used in medical care, namely in intensive care units. However, CVCs also represent one of the indwelling medical devices with enhanced risk of nosocomial device-related infection. Catheter-related infections (CRIs) are a major cause of patient morbidity and mortality, often justifying premature catheter removal and an increase in costs and use of resources. Adhesion and subsequent biofilm formation on the surfaces of indwelling catheters is elemental to the onset of pathogenesis. Seeking the prevention of CVC colonisation and CRI, a variety of approaches have been studied, tested and, in some cases, already applied in clinical practice. This review looks at the current preventive strategies often used to decrease the risk of CRIs due to colonization and biofilm formation on catheter surfaces, as well as at the more recent approaches under investigation.
Article
Eugenol is a phenolic monoterpenoid, emplyed in this study to obtain bio-based antimicrobial and antioxidant methacrylate polymers.
Chapter
Biomedical devices play an integral role in restoring bodily functions that have been impaired by disease. However, the ability of bacteria to adhere to biomaterials and promote the formation of biofilms causes medical devices to carry a definite and significant risk for promoting bacterial infection. Throughout the years, extensive research has focused on preventing microbial colonization on biomaterials via two dominant approaches: an active approach with the objective of killing adhered bacteria and a passive approach that prevents adhesion of bacteria. This chapter will discuss and highlight the design, development, antibacterial mechanisms, toxicity, and major applications of several antimicrobial coatings and systems.
Article
The transport properties of films based on chitosan and a drug have been studied, and sorption and diffusion characteristics of the films have been examined. The calculated diffusion coefficients and the abnormal kinetic curves of amikacin release have been discussed. An analysis of the obtained data showed that the process of drug transport from chitosan films deviated from the classical Fick’s laws due to structural changes in the polymer matrix induced by its chemical modification because of interaction with the drug.
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In order to create new biodegradable systems for the targeted transport of drugs, poly(3-hydroxy-butyrate) films containing the antibiotic rifampicin in an amount of 5–15 wt % as a model drug are prepared. Film surfaces are studied via scanning electron microscopy, and various structural elements (globules and fibrils) are found. Polymer samples isolated from melt or solution feature different degrees of porosity. It is shown that the kinetic profiles of rifampicin release are of an abnormal character. An analysis of the profiles shows that the release of rifampicin is controlled by the superposition of two processes: its desorption via the diffusion mechanism (the nonlinear segment) and hydrolytic degradation of poly(3-hydroxybutyrate) (the extended linear segment), which becomes well defined after completion of the diffusion stage. The diffusionkinetic model of the process is developed.
Article
A novel electrochemical biosensor was developed for activity assay of DNA methyltransferase and its inhibitor based on methylation-sensitive cleavage, which activated a primer for terminal transferase-mediated extension of biotinylated dUTP followed by sensitive detection via enzymatic amplification.
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Silane coated glass microspheres embedded in an epoxy polymer matrix have been employed as a model system to investigate water sorption at three water activities. Composites containing soda-lime-silica (A) glass in the range 0–25% by volume were tested in deionized water, saturated NaCl and saturated MgCl2, at 40°C. Increase in water activity led to a decrease in the effective water diffusivity due to trapping, especially at interfaces ruptured by osmotic pressure. Higher water activities favoured interfacial water transport, whereas lower water activities favoured water transport through the bulk of the polymer. Electrical resistance and water permeation tests suggested very rapid preferential water transport through areas of low cross-link density, even in the pure polymer, enhanced by the introduction of interfaces. Effective diffusivity calculations during water absorption and desorption, together with electrical resistance measurements and water uptake measurements in saturated NaCl, suggested the formation of a pecolating liquid channel network for composites containing more than 15% glass. Electrical resistance measurements using silver-coated A-glass/epoxy composites located the percolation threshold at 16% glass. Similar water sorption effects were observed with uncoated A-glass filled epoxy composites.
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To study the physical state of water in microcrystalline cellulose (MCC) and in silicified microcrystalline cellulose wet masses and the effect of granulation on different water fractions. Thermoporosimetry, together with the solute exclusion technique, was used to measure different water fractions and pore size distributions of wet granules. To understand the effect of granulation on the physical state of water, both ungranulated and granulated wet masses were studied. In addition, dynamic and isothermal step melting procedures were compared. Four distinct fractions of water (nonfreezing, freezing bound, free, and bulk water) could be detected in MCC wet masses. Granulation decreased the volume of bulk water and increased the volume of freezing bound and free water. Consequently, granulated wet masses were able to hold more water inside the particles compared to ungranulated wet masses. Thus, granulation had a similar effect on MCC as beating has on cellulose fibers in the papermaking proces Thermoporosimetry and solute exclusion increased the understanding of MCC-water interaction and showed how the physical state of water in MCC wet masses changes during granulation.
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Drug delivery to the brain is becoming more and more important but is severely restricted by the blood-brain barrier. Nanoparticles coated with polysorbates have previously been shown to enable the transport of several drugs across the blood-brain barrier, which under normal circumstances is impermeable to these compounds. Apolipoprotein E was suggested to mediate this drug transport across the blood-brain barrier. In the present study, apolipoprotein E was coupled by chemical methods to nanoparticles made of human serum albumin (HSA-NP). Loperamide, which does not cross the blood-brain barrier but exerts antinociceptive effects after direct injection into the brain, was used as model drug. Apolipoprotein E was chemically bound via linkers to loperamide-loaded HSA-NP. This preparation induced antinociceptive effects in the tail-flick test in ICR mice after i.v. injection. In contrast, nanoparticles linked to apolipoprotein E variants that do not recognize lipoprotein receptors failed to induce these effects. These results indicate that apolipoprotein E attached to the surface of nanoparticles facilitates transport of drugs across the blood-brain barrier, probably after interaction with lipoprotein receptors on the brain capillary endothelial cell membranes.
Article
The silver coating of polymers has been intensively investigated in the last few decades as an effective non-resistance-inducing strategy to prevent medical device-related infections. We have developed a completely new approach to incorporate silver ions in polymers by the synthesis of a carboxylated polyurethane able to coordinate Ag(+). The obtained polymers possess mechanical properties suitable for the development of medical devices, without any risk of loss of activity. To minimize the risk of increasing antibiotic resistance, the metal ion-containing polymers are loaded with ciprofloxacin, which possesses a different mechanism of antimicrobial action, thus a system able to inhibit Staphylococcus epidermidis and Pseudomonas aeruginosa growth for at least one month is developed.
Article
Hydroxyl-terminated polybutadiene-based (HTPB) polyurethane (PU) with different molar ratios of dimethyol propionic acid and 1,4-butane diol as the chain extender was synthesized by solution polymerization. The present PU was then cast into a membrane and subsequently characterized by the Fourier transform infrared spectroscopy. It was found that the participation of carbonyl group in hydrogen bonding increased with the content of dimethyol propionic acid in PU. The properties of the PU films including tensile strength and dynamic mechanical analysis (DMA) were studied. The tensile strength of PU films increased whereas the storage modulus decreased with increasing dimethyol propionic acid content. The glass transition temperature (Tg) of the PU film with only 1,4-butane diol as the chain extender was 4°C, while that of the films with dimethyol propionic acid as the chain extender was at about −15°C. Wettability and protein adsorption on the films were evaluated from the water content, contact angle, and protein adsorptions of fibrinogen and albumin on the PU films. The diffusion coefficient of water in the membrane was determined in accordance with the Fickian diffusion mechanism. No significant difference in the diffusion coefficient was observed for all the specimens. By using the Kaelble’s equation and the contact angle data, the surface tensions of the PU films with different amounts of dimethyol propionic acid were determined. The surface tension of PU film was found to increase with increasing dimethyol propionic acid content, while the opposite trend was observed for the contact angle and the amount of protein adsorption.
Article
In this study we have investigated the state of water in a superabsorbing network based on hydroxyethylcellulose (HEC) and carboxymethylcellulose sodium salt (CMCNa) crosslinked with divinylsulfone (DVS).This type of network, at low degree of crosslinking, when exposed to distilled water is able to form a stable hydrogel containing an amount of water as high as 1000 times its own weight.De-hydrated/re-hydrated networks, containing different amounts of absorbed water, have been studied using differential scanning calorimetry (DSC) and NMR relaxometric methods. DSC analysis allowed the evaluation of freezable and non-freezable fractions of absorbed water showing also the presence of two types of freezable water. On the other hand, NMR relaxometry evidenced the presence of two hydration shells, characterized by a different mobility, which in both cases is lower than that of bulk water.An excellent quantitative agreement was found in the determination of the amount of freezable water using the two techniques.A comparison of the state of water in the crosslinked network and in the corresponding uncrosslinked mechanical mixture shows that in the last case micro-heterogeneity arises.
Article
The first direct synthesis of a carboxylated polyurethane is described. The polyurethane, of the segmented type, was obtained by reaction of 4,4′-diphenylmethane diisocyanate with poly(propylene oxide) and the tributylammonium salt of dihydroxymethylpropionic acid. The polymer was characterized by viscometry, DSC, i.r. and NMR spectroscopy. The reactivity of the free carboxylic group in the polymer was evaluated for esterification and amidation.
Article
Water dynamics and compartmentation in glutaraldehyde cross-linked bovine serum albumin nanoparticles have been investigated by an integrated nuclear magnetic resonance (NMR) protocol based on water relaxation times and self-diffusion coefficients measurements. Multi-exponentially of water relaxation curves has been accounted for according to a diffusive and chemical exchange model (see B. P. Hills, S. F. Takacs and P. S. Belton, Mol. Phys., 1989, 67(4), 903, and Mol. Phys., 1989, 67(4), 913; E. Brosio, M. Belotti and R. Gianferri, in Food Science and Technology: New Research, ed. L. V. Greco and M. N. Bruno, Nova Science Publishers, Hauppauge (NY), 2008) that made it possible to single out water molecules in the molecular spaces in the interior of albumin nanoparticles, in the meso-cavities formed by packed nanoparticles and in the meniscus on top of the nanoparticles suspension. A quantitative rationalization of T2 values of water different components allowed morphological information to be acquired as for the size of water filled compartments, while self-diffusion coefficient measurements of water excess or fluxed packed nanoparticles suspensions are describers of transport properties of soft biomaterials. The paper reports an NMR approach that can be seen as a general and relevant method to characterize excess-water-swollen soft biomaterials.
Article
Proton conducting membranes were prepared by irradiation grafting with styrene followed by sulfonation on matrices of poly(vinylidene fluoride), PVDF. Membranes crosslinked with divinylbenzene and/or bis(vinylphenyl)ethane were compared to non-crosslinked membranes. The ion conductivity of the crosslinked membranes is lower than that of the non-crosslinked membranes. This is due partly to the very inefficient sulfonation of the crosslinked membranes below the graft penetration level, which in turn leads to a low water uptake at low degrees of grafting. The graft penetration level is lower in crosslinked membranes than in non-crosslinked membranes. This leads to a more compact structure of the crosslinked grafts within the matrix. The lower ion conductivity in the crosslinked membranes is therefore partly also due to restricted mobility of the ion clusters necessary for ion and water transport in the membranes.
Article
New results of dielectric spectroscopy in semicrystalline nylon-6 samples with different moisture contents are presented by using a wide frequency (10-2−3 × 106 Hz) and temperature range (133−433 K). The dielectric absorption spectra in frequency domain are decomposed in Cole−Cole distributions corresponding to the local γ and β modes, two segmental α modes, and a high-intensity Maxwell−Wagner−Sillars relaxation. The presence of two segmental relaxations in the isothermal runs, attributed to the plasticized and the unplasticized α mode, is interpreted as the manifestation of two different length and time scales of cooperative motions. A quantitative comparison between the results obtained for the wet and dry samples, such as relaxation times variation, activation energies, Vogel−Tammann−Fulcher parameters, dielectric increments, and distribution widths, is presented for each mode and shows how the progressive drying of the sample during the experiment affects all these quantities.
Article
A poly(vinyl alcohol) hydrogel was prepared by coupling poly(vinyl alcohol) with epichlorohydrin as cross-linking agent. Various amounts of water were added into the dry hydrogel to swell it and the quantity of water in various states in the partially swollen hydrogel were determined by DSC ice-melting technique. A parameter S denoted the degree of the saturation of swelling was introduced for describing the various stages of water absorption. The analytical results indicate that there exists two critical threshold degree of saturation. At the first threshold S*, the freezable bound water starts to appear and at the second threshold S**, the free water begins to appear. In the region of S
Article
The temperature of crystallization and of melting of water in poly(vinyl alcohol) (PVA) membranes with various degrees of acetylation have been measured at different cooling and heating rates, and compared to the glass transition temperature (Tg) of the swollen materials. Above a certain critical concentration of water, c∗, when water begins to crystallize upon cooling, the Tg does not decrease according to the Fox equation, but remains constant. This phenomenon of regulation of the Tg and the origin of c∗ are explained by the phenomenon of segregation of water in the amorphous phase during the process of crystallization. Finally, the effects of melting temperature depression and of broadening of the melting peak of ice in PVA—water systems, very similar to those observed in saccharose—water and alcohol—water mixtures, are explained by the phenomenon of dissolution, and not by the confinement effect.
Article
Two kinds of aqueous dispersions were prepared from waterborne polyurethane (WPU) and its prepolymer by mixing (M) and grafting (G) with 10 wt % casein, respectively. The resulting dispersions were characterized by using a rotary viscometer and a particle size distribution meter, indicating that the viscosity, Z average size, and polydispersity of the dispersions increased with an increase of the casein content, and the average particle size of the M dispersions (ca. 30−50 nm) was much lower than that of the G dispersions (ca. 50−150 nm). Polyurethane/casein composite sheets were prepared from the dispersions M and G, coded as sheets M and G, respectively. The structure and properties of the sheets were characterized by using infrared spectroscopy, scanning electron microscopy, ultraviolet spectrophotometry, dynamic mechanical analysis, and tensile testing. The results revealed that the sheets M and G all exhibited a certain degree of miscibility, and their tensile strength was much higher than that of the sheet of pure WPU. When the casein content was 6 wt %, the tensile strength (σb) and elongation at break (εb) of the G sheet in a dry state achieved 30.1 MPa and 775%, respectively. When the casein content was 4 wt %, the values of σb and εb of the M sheet in a dry state were 32.4 MPa and 1073%, respectively. Interestingly, the values of σb and εb of the M sheets prepared from mixing dispersion were larger than those of the G sheets, suggesting that the effect of casein/WPU composite nanoparticles dominated, even over that of the WPU grafted with casein. Moreover, the miscibility of the M sheets was higher than that of the G sheets because of the larger specific surface of the nanoparticles. The particle size and content of casein in the aqueous dispersions containing WPU play an important role in the enhancement of mechanical properties of the composite sheets M and G.
Article
Der Einfluß verschiedenartiger niedrigmolekularer Quellungsmittel auf die mechanischen Eigenschaften von Polyurethan wurde in einem Temperaturbereich von −180°C bis etwa 50°C oberhalb der Glastemperatur mit Hilfe von freien Torsionsschwingungen bei konstanter Frequenz von 1 Hz untersucht.Während man bei ungequollenem Material nur zwei Relaxationsgebiete beobachtet (α-Maximum bei etwa +40°C und α-Maximum bei etwa −135°C), erscheint bei Quellungsmittelzusatz ein drittes Relaxationsgebiet bei etwa −70°C (β-Maximum).Die Temperaturlage des α-Maximums verschiebt sich mit steigender Konzentration an Quellungsmittel zu tieferen Temperaturen. (Das ist gleichbedeutend mit einer Erniedrigung der Glastemperatur.) Diese Erniedrigung ist bei allen untersuchten Systemen – mit Ausnahme des Systems Polyurethan/Wasser – dieselbe, wenn man die Konzentration des Quellungsmittels im Grundmolenbruch angibt. Auf Grund dieser Meßergebnisse werden Rückschlüsse auf die Art der Bindung der Quellungsmittelmoleküle im Polymeren gezogen.The influence of various low-molecular solvents on the dynamic mechanical properties of polyurethane has been studied over a temperature range extending from −180°C. up to about 50°C. above the glass transition using a torsional pendulum at constant frequency of 1 cps.In dry specimens the temperature dependence of the mechanical loss factor tg δ and also of the imaginary part G″ of the complex dynamic modulus shows two maxima: α-maximum at +40°C. and β-maximum at −135°C. In swollen polyurethane there is a third maximum at −70°C. (β-maximum).The glass temperature, Tg, decreases with increasing content of solvent. Besides of the system polyurethane/water, all investigated solvents show the same lowering of Tg when the concentration of the solvent is marked in base mole fraction. Molecular considerations due to these results are given.
Article
Heparin was bonded covalently to hydrophilic polyurethanes. Polymers were characterized by spectroscopic techniques (IR and 1H, 13C NMR), molecular weight measurements and differential scanning calorimetry. The heparin content of the polymer films (up to more than 500 μg/cm2) was determined by a calorimetric system, and its biological activity was evaluated in vitro by APTT (activated partial thromboplastin time) measurements with a tenfold increase of the clotting time (about 300 s) with respect to the clotting time of human plasma (30 s). When heparin is bonded to a polymer provided with a hydrophilic polyfunctional spacer, the heparin content of the films is remarkably higher than previously described (about twice the reported values), and also the biological activity of the bonded heparin is favourably affected.
Article
Equilibrium and dynamic sorption isotherm measurements, differential scanning calorimetry (DSC) measurements, and, mainly, dielectric relaxation spectroscopy (DRS) measurements by means of the thermally stimulated depolarization currents (TSDC) method were used to investigate the hydration properties of linear segmented polyurethane copolymers. Three types of samples were investigated with various fractions of hard and soft block segments. They were based on polyethylene adipate (PEA), 4,4′-diphenylmethane diisocyanate (MDI) and 1,4-butanediol (BDO). At 20°C the water content h of the samples at various values of relative humidity rh increases in proportion to the weight fraction of soft block segments phase. At saturation (rh = 100%) the ratio of sorbed water molecules to polar carbonyl polyester groups is 0.13. At saturation at 20°C there is no fraction of freezable water. The glass transition temperature, Tg, measured by DSC and by TSDC, shifts to lower temperature with increasing h by about 8–10 K at saturation at 20°C. A dielectric relaxation mechanism related to interfacial polarization in the phase-separated morphology is also plasticized by water in a way similar to that observed for the main (α) relaxation. © 1996 John Wiley & Sons, Inc.
Article
The depression of the glass transition temperature by water was studied in a set of polyurethanes in which the soft segment consisted of polyethylene oxide (sample I) or a block copolymer of poly(propylene oxide) terminated with poly(ethylene oxide) in various proportions (sample set II). DSC measurements were made at two added water contents for each type of sample and at various temperatures. The Tg reduction appeared to be governed solely by the nonfreezing bound water and was much larger in sample I than in samples of set II. The more limited effect on the Tg of set II samples is attributed to restricted mobility arising from coupling of the short terminal poly(ethylene oxide) to rigid hard-segment units. Therefore, the data for sample I are preferred as a test of the predictive relations for the Tg depression. On this basis, it appears that the simple Fox mixing equation is more reliable than is the available free volume approach, which required unrealistically high values of the thermal expansion coefficient for water to fit the data for sample I. © 1993 John Wiley & Sons, Inc.
Article
The structure of water molecules sorbed in different hydrophilic polymers was studied by DSC and FTIR. The obtained data shows that, first, the sorbed water molecules are directly bound to the hydrophilic site to form non-freezable water. Then, beyond a certain water content threshold, the sorbed water molecules become freezable, but with a melting point lower than 0°C, due to their location in the second hydration layer. Bulk-like water which can be frozen at 0°C appears at higher water contents, and the two types of freezable water finally merge together at very high water contents. The average number of non-freezable water molecules per site depends on the chemical nature of the polar site: ca. 1 for a hydroxyl, and 4.2 for an amide group. For a polymer with carboxylate sites, it increases with the size of the alkaline counter-ion of the site, due to the increasing ability of the carboxylate counter-ion pair to undergo dissociation.
Article
A solid made from a dissolved mixture of hydroxypropylcellulose and ethylcellulose (SMH) was used as a controlled-release filler, and phenylpropanolamine hydrochloride (PPA) was used as a model drug. With increases in weight fraction of hydroxypropylcellulose (WFH) in the matrix, drug release and water penetration into the matrix decreased Water behavior daring drug release from a SMH matrix was studied by using differential scanning calorimetry (DSC). During the initial stage of dissolution, the water penetrating into the matrix acted as non-freezing water. As the water content of the matrix increased and freezable water was detected at levels that were related to drug release. It was also presumed that before hydrating the whole matrix, water penetrated into the dry portion of the matrix and hydrated the polymer, while further penetrating water did not increase the water content of the hydrated portion, but newly hydrated a dry portion of the matrix.
Article
Sisal nanowhiskers were used as novel reinforcement to obtain nanocomposites with polyvinyl acetate (PVAc) as matrix phase. They are seen as attractive materials due to the widespread availability and low cost of the sisal source material. Statistical analysis of the sisal whisker length and diameter resulted in average values of 250nm and 4nm, respectively, resulting in an average aspect ratio in the upper range of reported cellulose nanowhisker values. The high aspect ratio ensures percolation, with resulting mechanical improvements and thermal stability, at lower fiber loads. Water uptake and thermal behaviour of the sisal whisker–PAVc composites were studied. Whisker addition was found to stabilize the nanocomposites with no benefit seen when increasing the whisker content beyond the percolation threshold: For all whisker contents studied above percolation, the water uptake stays constant, and the Tg does not vary with whisker content at a given relative humidity. The water diffusion rate however increases due to water accumulation at the whisker–PVAc interface. Below whisker percolation, stabilization is only noticed at low relative humidity, whereas high humidity results in disruption of whisker–PVAc interactions. This work shows the potential of cellulose nanowhiskers to stabilize polar polymers even at high humidity conditions with minimal reinforcement addition.
Article
Nanocomposite materials were prepared using sorbitol-plasticized pullulan as the amorphous matrix and an aqueous suspension of starch nanocrystals (prepared by submitting native granules from waxy maize starch to acid hydrolysis at 35 °C) as the reinforcing phase. Wide-angle X-ray diffraction analysis showed an increase of the crystallinity of the composite biopolymer films with increasing of starch nanocrystal content. The water absorption isotherms and kinetics as well as the water barrier properties of nanocomposite films filled with 0–40% (w/w) starch nanocrystals (starch nanocrystals/pullulan + sorbitol) were investigated. The water uptake of pullulan–starch nanocomposites decreased with increasing filler content whereas water vapor permeability (measured at 25 °C and 53/100 relative humidity (RH) gradient) remained constant up to 20% (w/w) and, then decreased significantly with further addition of nanocrystals. The thermo-mechanical behaviour of nanocomposite films was also investigated by means of dynamic mechanical thermal analysis (DMTA) and large deformation mechanical tests (tensile mode). The glass transition temperature (Tg) shifted towards higher temperatures with increasing amount of nanocrystals, which can be attributed to a restriction of the mobility of pullulan chains due to the establishment of strong interactions not only between starch nanocrystals but also between the filler and the matrix. Moreover, the addition of nanocrystals caused strong enhancement of the Young modulus and the tensile strength, but led to a drastic decrease of the strain at break in samples conditioned at different environments (from 43% to 75% RH).
Article
Various natural and synthetic polymers with hydrophilic groups, such as hydroxyl, carboxyl and carbonyl groups, have either a strong or weak interaction with water. Thermal properties of polymers and water are both markedly influenced through this interaction. The first-order phase transition of water fractions closely associated with the polymer matrix is usually impossible to observe. Such fractions are called non-freezing water. Less closely associated water fractions exhibit melting/crystallization, showing considerable supercooling and significantly smaller enthalpy than that of bulk water. These water fractions are referred to as freezing bound water. The sum of the freezing bound and non-freezing water fractions is the bound water content. Water, whose melting/crystallization temperature and enthalpy are not significantly different from those of normal (bulk) water, is designated as freezing water. Bound water in the water-insoluble hydrophilic polymers, such as cellulose, lignin and poly(hydroxystyrene) derivatives, breaks hydrogen bonding between the hydroxyl groups of the polymers. The bound water content depends on the chemical and high-order structure of each polymer. Aqueous solutions of water-soluble polyelectrolytes, such as hyaluronic acid, gellan gum, xanthan gum and poly(vinyl alcohol) form gels above a threshold concentration. In the above gels, water mostly exists as the freezing bound water, playing an important role in the junction zone formation. It has also been observed that various kinds of polysaccharide polyelectrolytes with mono- and divalent cations, and other polyelectrolytes, such as polystyrene sulfonate, form thermotropic/lyotropic liquid crystals in the water content, ranging from 0.5 to ca. 3.0 g of water/g of polymer.
Article
DSC profiles and relaxation NMR 1H signals were used to characterise highly hydrated milk protein dispersion (3 to 20 g per 100 g DM) with various micellar casein concentrations (3–15 g per 100 g of dispersion), whey protein concentrations (0–3 g per 100 g of dispersion), lactose concentrations (0–7.5 g per 100 g of dispersion), CaCl2concentration (0–2 mM) and pH (6.2–6.6). Results obtained with both techniques showed the predominant effect of micellar casein and lactose concentrations on the water state. Heat of fusion of water and amount of unfreezable water (0.49 g/g for dispersions without lactose and 0.60 g/g for lactose containing dispersions) measured by DSC varied mainly in lactose and native phosphocaseinate (NPC) content. Furthermore, NMR water relaxation behaviour was consistent with a three site relaxation model. Because of fast diffusive exchange, the relaxation rate observed was the sum of the free water relaxation rate, the hydration water relaxation rate and the exchangeable protons relaxation rate, weighted by their relative proportions. Analysis of the variation in relaxation rate with the sample composition confirmed that the hydration water was mainly influenced by the casein concentration and that the chemical exchange effect, such as the lactose effect, could be attributed to soluble macromolecules. NMR versus DSC results were also discussed.
Article
The polyester polyurethanes, PU based on isophoronediisocyanate, polycaprolactone, and 1,4-butanediol with different amounts of functional groups introduced into the hard segments via second chain extender, 2,2′-bis-(hydroxymethyl) propionic acid, were investigated by electron spin resonance, ESR, spin label method, wide-angle X-ray diffraction, WAXD, optical microscopy and differential scanning calorimetry, DSC. The objective of this study is to clarify the effect of functional groups on the motional heterogeneity, microphase separation and crystallisation of the polyurethanes. The concentration of carboxylic groups varied from 0 to 0.45 mmol g−1. The temperature-dependent ESR spectra of spin labelled PU hard segments chain ends with stable nitroxide radical 2,2,6,6-tetramethyl-4-aminopiperidin-1-yloxyl are sensitive to the amount of functional groups attached to the hard segments. Composite ESR spectra of functionalized PU, with fast and slow component, suggest that PU hard segments are partitioned in two motionally different environments. According to the ratio of fast and slow component motional heterogeneity increases with an increase of functional groups up to 0.35 mmol g−1 and above this concentration slow component decreases indicating higher degree of phase mixing and stronger effect of soft segments. Polarized micrographs and the extent of ordering from WAXD measurements reveal the changes of phase morphology with the carboxylic groups content in a similar way as shown from the motional behaviour of spin label on the segmental level. The degree of crystallinity and the separation of spherulitic rings are decreasing above a certain concentration of functional groups. The effect of functional groups in PU on the hard and soft segment mixing is discussed in terms of additional noncovalent interactions and chain structure which at critical level of interactions lead to a formation of more open hard segment structure accessible to interaction with the soft segment.
Article
The mobility of hydration water and the dissolved oxygen permeability through different cation forms of the Nafion® membranes were determined. Two alkali metals (Na and K) and two amino sugars (an equivalent molar mixture of d-glucopyranosyl-α(1′ → 6)-2-amino-2-deoxy-d-mannitol and its sorbitol (GPA)and d-glucosamine (GLU)) were used as counterions. Based on the two-state model, the content and mobility of hydration water were determined using DSC and 17O NMR. The dissolved oxygen permeability through the Nafion® membrane containing GPA was the lowest value in this study because, for the membrane, the fraction of hydration water was the greatest and the mobility of hydration water was the lowest. The amount and location of the hydrophilic group contained in substances as well as the kind of hydrophilic group affected the fraction and mobility of hydration water and dissolved oxygen permeability through the membranes.
Article
Organic–inorganic polymer composites, consisting of a polyurethane organic phase and a mineral inorganic phase were prepared by the joint polymerization of the urethane oligomer with the water solution sodium silicate. The structure and the morphology of the composites, at a fixed weight fraction of the inorganic component of 20%, and of the corresponding pure polyurethane matrices were investigated by wide-angle and small-angle X-ray scattering (WAXS and SAXS, respectively). The results show similar size (5–7 nm) of the scale of heterogeneity of the composites due to the microphase separation of the rigid and the flexible blocks of the amorphous polyurethane matrix and due to the inorganic crystalline inclusions, i.e. the materials prepared are nanocomposites. The WAXS measurements indicate that the individual properties of the block inorganic component are lost in the nanocomposites, probably due to physical and chemical interactions between the two components. Water sorption from the liquid phase was studied gravimetrically in a composite and in the corresponding polyurethane. The results show high sorption capacity of the composite, due to the hydrophilicity of the inorganic phase and the elasticity of the polyurethane matrix, and allow to estimate the layer thickness of water adsorbed on the inorganic nanoparticle surface to about 20 nm, in reasonable agreement with a model adopted from the literature. WAXS and SAXS measurements on the swelled composite and the swelled-and-dried composite indicate changes in the structure of the inorganic component induced by water, which are, however, to a large extent reversible. These materials may find applications as gel electrolytes and as hydrogels in drug delivery systems.
Article
Organic–inorganic polymer membranes were prepared by reacting 3-glycidoxypropyl trimethoxysilane with diamines containing polyether segments, followed by hydrolysis and condensation with acid catalysis. The films were characterized by nuclear magnetic resonance and by dynamic mechanical analysis. The rigidity of the films increased with increasing epoxy content and also with addition of tetraethoxy silane (TEOS) to the reacting medium. Water absorption experiments showed that the diffusivity is decreased with increasing TEOS content. Membranes were evaluated for nanofiltration giving cut offs down to 860 g/mol (with a water flux of 2.5 l/h m2 bar). For gas separation, CO2/N2 selectivity values up to 89 were obtained with CO2 permeability of 125 Barrer.
Article
In recent years the employment of implantable medical devices has increased remarkably, notwithstanding that microbial infections are a frequent complication associated with their use. Different strategies have been attempted to overcome this problem, including the incorporation of antimicrobial agents into the device itself. In this study a new approach to obtain intrinsically antimicrobial materials was developed. Polymer anionomers containing Ag(I), Cu(II), Zn(II), Al(III) and Fe(III) were prepared by neutralization of a carboxylated polyurethane. In the case of the PEUA-Ag, PEUA-Fe and PEUA-Cu ionomers the ion aggregates behaved as reinforcing filler particles, increasing the mechanical properties of the systems in terms of hardness and strength at break over the pristine carboxylated polymer. With the exception of the Al-containing polymer, all the other experimented ionomers showed satisfactory antimicrobial properties. The best antibacterial effect was obtained with the silver ion-containing polymer, which inhibited Staphylococcus epidermidis growth for up to 16days. Ciprofloxacin was also adsorbed onto the above mentioned ionomers. A synergistic effect of the antibiotic and silver ions on bacterial growth inhibition was observed for at least 25days.
Article
Nano-structured polymers delivering an antibiotic for the prevention of medical device-related infections were developed. Systems consisted of bovine serum albumin or polyallylamine nanoparticles alone or entrapped in a polyurethane and then loaded with cefamandole nafate, chosen as a drug model. Results showed that nanoparticles alone were able to adsorb high antibiotic amounts due to their high surface/volume ratio. However, they released cefamandole in an uncontrolled fashion, leading to a rapid loss of antibacterial activity. Improvements in the release control were obtained when CEF loaded and non-loaded nanoparticles were entrapped in a carboxylated polyurethane. For these systems the drug delivery was at least of 50% with respect to nanoparticles alone with a prolonged antimicrobial activity up to 9 days.
Article
Hydrogel films were prepared from hydroxyethyl methacrylate, both with (Film II) and withouth (Film I) 5.25 mole% of ethylene glycol dimethacrylate. Permeation, diffusion, and partition coefficients for progesterone, testosterone, nandrolone, norethindrone, 17 alpha-hydroxyprogesterone, estradiol, and hydrocortisone were determined. A solute permeation model was proposed based on the separation of a domain (B) composed of "bulk-like" water and a doman (A) composed of polymer, interfacial water, and bound water present in the films. The separate contributions from the "pore" and "solution-diffusion" mechanisms to the total permeability were calculated from the model. Steroid permeabilities through Films I and II were analyzed in accordance with this model. Permeation of Film II occurred via the solution-diffusion mechanism. Permeation of Film I occurred predominately by the pore mechanism with a small contribution (approximate 20%) from the solution-diffusion mechanism. The latter contribution was dependent on the solubility of the solute within the A domains of the hydrogel film. Functional group contributions to permeation of Film II were ascribed to either steric or hydrogen bonding effects.
Article
The synthesis of a new segmented polyurethane containing quaternary ammonium groups in the side-chain is reported. The quaternization was carried out both on the polymer dissolved in an organic solvent and on polymer films. Polymeric films quaternized by both techniques were heparinized. The amount of bonded heparin, determined by spectrophotometry, was remarkably higher than previously described. Polymer quaternized in solution bonded more heparin than that heparinized directly on film. In vitro evaluations of antithrombogenicity by activated partial thromboplastin time (APTT) carried out on the films confirmed these data. The polymers were also characterized by chemical, i.r., n.m.r., differential scanning calorimetry and viscometric techniques.
Article
Bovine serum albumin nanospheres (BSA-NS), prepared with glutaraldehyde cross-linking and ultrasonication, were coated with antibodies by covalent linkage (Schiff's base formation) of aldehyde groups at the surface of the nanospheres with amino groups of the antibody. The coating was confirmed using Fluorescein isothiocyanate which conjugates with antibodies and also by the antigen-antibody interaction using Sepharose beads. Rapid in vitro degradation of BSA-NS was first confirmed by incubating a radioactive nanosphere suspension at 37 degrees C in 0.25 M sucrose solution with 1% liver or lung extract. The radioactive compound conjugated BSA-NS suspension was then administered to mice intravenously, and tissue distribution of BSA-NS was examined using whole body autoradiography; the BSA-NS were found to be localized mainly in the liver, the lungs and the kidneys and 4 hr and 24 hr after injection, almost all radioactivity had disappeared except for that in the kidneys. The binding ratio of monoclonal antibodies to tumor cells in vitro was found to be 2-2.5 times greater than that of control antibodies (mouse IgG) by means of a gamma ray counter. An in vivo binding test showed that monoclonal antibodies might recognize the target organ (Lewis lung carcinoma). Applying these findings, BSA-NS coated with monoclonal antibodies were found to be trapped in the tumoral tissue of Lewis lung carcinoma-bearing mice more than in controls (BSA-NS coated with mouse IgG) at 24 hr after the injection. Thus, BSA-NS offer potential as useful drug carriers enabling concentration of drugs at specific target sites. Furthermore, their rapid elimination from the body and their degradability suggest that side effects due to long-lasting accumulation in several organs may be avoided.
Article
The objective of the present study was to characterise and optimise the desolvation process of human serum albumin (HSA) for the preparation of nanoparticles and to characterise the resulting colloidal system. Following the desolvation of the protein, the resulting nanoparticles were stabilised by the addition of varying amounts of glutaraldehyde or by heat denaturation. The particle size, zeta potential, and the number of available amino groups on the surface of the nanoparticles were determined. The amino groups were quantified by a spectrophotometric method using 2,4, 6-trinitrobenzenesulfonic acid (TNBS). The results indicated that the particle size depended mainly on the amount of desolvating agent added, but not on the amount of cross-linker or the kind of cross-linking procedure. Increasing amounts of glutaraldehyde reduced the number of amino groups on the surface of HSA nanoparticles and also decreased the zeta potential of the carrier system. The temperature and heat denaturation time only had an influence on the stability of the nanoparticles but not on the amount of amino groups or the particle size. It was shown that heat denatured HSA nanoparticles possessed the greatest number of amino groups on their surface. Additional experiments for the characterisation of gelatin A and B nanoparticles were performed.
Article
The present study was conducted to obtain a deeper insight into the mechanism of drug release from HPMC matrices. The microstructure, mobility, internal pH and the state of water within the gel layer of hydrated HPMC matrices (having different molecular weights) containing naproxen sodium (NS) and naproxen (N) were studied using Electron Paramagnetic Resonance (EPR), Nuclear Magnetic Resonance (NMR) and Differential Scanning Calorimetry (DSC) techniques. The study show that matrices composed of various viscosity grades of HPMC are characterized by similar microviscosity values in spite of the difference in their molecular weight. The NMR and DSC results led to the conclusion that higher molecular weights of HPMC are characterized by higher water absorption capacity and higher swelling. Analysis of non-freezable water in HPMC(K4M)-NS system revealed that addition of NS to solution increased the fraction of water bound to K4M+NS compared with the equivalent solutions without NS. The results suggest that the drug is participating in the crystallization of water and leads to the formation of a three dimensional network structure that decreases the freedom of water in K4M+NS samples. Calculation of the number of hydration shells showed that up to 2.2 layers are involved in HPMC-NS hydration compared to 1.5 layers for HPMC gel without NS. This was explained based on the different water ordering in the gel induced by NS as results of its absorption to polymer surface. Microviscosity values measured by EPR for K4M/N and K4M/NS hydrated matrices were found to be higher for K4M/N matrices, especially at initial stage of hydration. Mobile compartment calculations showed lower values for K4M/N compared with K4M/NS matrices. pH measurements by EPR revealed that incorporation of N to HPMC matrix led to lower internal pH value inside the hydrated tablet compared with NS. This behavior led to lower solubility of N which dictates its surface erosion mechanism, compared with NS matrix that was characterized by higher internal pH value and higher drug solubility. These properties of HPMC/NS increased chain hydration and stability, and led to drug release by the diffusion mechanism.
Article
Ganciclovir is one of the most widely used antiviral drug for the treatment of cytomegalovirus retinitis. Due to its short half-life in the vitreous, frequent administrations are necessary to maintain the therapeutic levels. In this context, the aim of this study was to characterise and in vitro evaluate the drug release properties of three different formulations of ganciclovir-loaded albumin nanoparticles. These carriers were prepared by a coacervation method and chemical cross-linking with glutaraldehyde. Depending on the step where the drug and/or cross-linking agent were added three different formulations were obtained, named models A, B and C. For model A nanoparticles, ganciclovir was incubated with the just-formed albumin nanoparticles. For the other two types of nanoparticulate formulations, the drug was added to a solution of albumin (model B) and glutaraldehyde (model C) prior to the formation of the carriers by coacervation. In all cases, the size of the different nanoparticulate formulations was comprised between 200 and 400 nm and the yield ranged from 50%, in model A, to 65% in model B. Concerning the ganciclovir loading, model B nanoparticles offered the higher capacity to carry this antiviral drug (around 30 microg ganciclovir/mg nanoparticle). On the contrary, the drug loading calculated for model A nanoparticles was only 14.6 microg/mg. The in vitro release profiles of the nanoparticles showed a biphasic pattern, with an initial and rapid release, followed by a slower step for up 5 days. This burst effect was especially relevant in model A (around 60% in 1 h), followed by model B (40%) and less important in model C (20%). The addition of trypsin to the release medium did not have a significant influence on the release characteristics. However, the release of the drug was increased in acidic or basic mediums, due to the disruption of the covalent binding between ganciclovir and the protein matrix via glutaraldehyde. This strong linkage was also confirmed by TLC experiences. In summary, a first step of incubation between the drug and the protein, prior to the preparation of nanoparticles, enabled us to obtain albumin carriers able to release ganciclovir in a sustained way.
Article
Heparin is a potent anticoagulant agent that interacts strongly with antithrombin III to prevent the formation of fibrin clot. In this study, we propose a new method for preparing a heparin-releasing system using a simple solvent casting. The heparin-DOCA conjugate, having an amphiphilic property, was homogeneously mixed with polyurethane in the co-solvent of dioxane, propanol and water. After casting the film, heparin-DOCA was homogeneously dispersed as nanoparticles in a polyurethane film. As the loading amount of heparin-DOCA in the film was increased, nanoparticle size, water uptake, and release rate were increased. Moreover, the percentage of released amount of heparin-DOCA was increased with the increase in the loading amount of heparin-DOCA. This was because the size of heparin-DOCA particles increases with the increase in the loading amount of heparin-DOCA, thereby decreasing the distance between particles and the total diffusion length to the surface. The release rate of heparin-DOCA can be controlled by the amount of the drug being loaded and the film thickness. When the heparin-DOCA loaded on the polyurethane films was above 7.5%, the released heparin-DOCA prevented the formation of fibrin clot and the platelet adhesion on the film surface.
Article
The objective of this article is to review the spectrum of mathematical models that have been developed to describe drug release from hydroxypropyl methylcellulose (HPMC)-based pharmaceutical devices. The major advantages of these models are: (i) the elucidation of the underlying mass transport mechanisms; and (ii) the possibility to predict the effect of the device design parameters (e.g., shape, size and composition of HPMC-based matrix tablets) on the resulting drug release rate, thus facilitating the development of new pharmaceutical products. Simple empirical or semi-empirical models such as the classical Higuchi equation and the so-called power law, as well as more complex mechanistic theories that consider diffusion, swelling and dissolution processes simultaneously are presented, and their advantages and limitations are discussed. Various examples of practical applications to experimental drug release data are given. The choice of the appropriate mathematical model when developing new pharmaceutical products or elucidating drug release mechanisms strongly depends on the desired or required predictive ability and accuracy of the model. In many cases, the use of a simple empirical or semi-empirical model is fully sufficient. However, when reliable, detailed information are required, more complex, mechanistic theories must be applied. The present article is a comprehensive review of the current state of the art of mathematical modeling drug release from HPMC-based delivery systems and discusses the crucial points of the most important theories.
Article
Previously, we reported that poly(2-methoxyethylacrylate) (PMEA) showed excellent blood compatibility and implied that the water structure in PMEA contributed to the blood compatibility. In this study, the relationship between the water structure and the blood compatibility is clarified by studying the influence of the monomer composition of poly(MEA-co-HEMA) on the water structure and the blood compatibility of the copolymers. The water in the polymer was classified into three types: free water, freezing bound water, and nonfreezing water. The polymers with 0-30 mol % of HEMA content had a significant amount of freezing bound water, and the amount decreases greatly when the composition of HEMA exceeded 30 mol %. On the other hand, the amount of other water increased simply with an increase of HEMA content. The evaluation of the platelet compatibility of poly(MEA-co-HEMA) revealed that the adhesion number and the morphological change of platelet on the copolymer surface were least when the HEMA content was 0-20 mol %. These two results strongly suggest that the freezing bound water relates to the platelet compatibility of the polymers.
Article
For the purpose of selecting the efficient dispersion condition of hydrophilic semiconductor quantum dots (QDs) in biological buffers, the dispersion of the QDs mixed with a serum albumin from 9 different species or an ovalbumin was compared by a fluorescence intensity analysis. The QDs mixed with sheep serum albumin (SSA) showed the highest fluorescence of all when the mixtures were dissolved in Dulbecco's MEM. QD/SSA complexes were accumulated in the endosome/lysosome of Vero cells and the fluorescence could be detected over a 5-day post-incubation period. The photostability of QD/SSA complexes associated with the endosomes was detectable, at least, 30 times as long as that of fluorescein-labeled dextran involved in endosomes. QD/SSA complex, therefore, can be used as a long-life and highly photostable endosome marker.
Article
Intravascular devices are widely used for vascular access but are associated with substantial risk of development of devices-related bloodstream infection (DR-BSI), which causes a considerable increase of morbidity and mortality, prolonged hospitalisation and growing medical costs. Since conventional treatment of DR-BSI fails in a significant number of cases, resulting in removal of the device, new approaches are needed to prevent bacterial colonization. In this paper, two antibiotics, rifampin and amoxicillin, have been adsorbed on polyurethanes exhibiting acidic or basic properties. The influence of the type of antibiotic-polymer interaction on the amount of adsorbed antibiotic and on the release kinetics was studied. It was seen that the antibiotic-polymer affinity increases both with the introduction in the polymer side-chain of functional groups and with the matrix hydrophilicity. The antimicrobial activity of the treated polymers, evaluated in vitro by the Kirby-Bauer test, depends on the amount of antibiotic adsorbed, on the strength of drug-matrix interaction and on the water swelling of the polymers. The inhibition zone of bacterial growth lasts only a few hours for the amoxi-coated polymers while remains at least for five months for the rifampin-coated ones. The presence of serum proteins decreases by about 30% the inhibition zone diameter of these latest matrices after two months.
Article
Acidic or basic polyurethanes were loaded with antibiotics to develop materials to prevent medical device-related infections. A correlation between polymer-antibiotic interactions and amount of drug absorbed by polymers and released over time was found. Since the employed antibiotics, i.e. amoxicillin, cefamandole nafate, rifampin and vancomycin, possessed at least an acidic group in their structural formula, the introduction of basic tertiary amines in the polyurethane side-chain resulted in an increased polymer ability to adsorb antibiotics. However, a stronger ionic interaction between this polymer and the antibiotics caused a release of lower amount of drug over time. Antibiotics released from polymers inhibited Staphylococcus epidermidis growth on agar. Antibiotic-loaded polyurethanes kept in water for increasing times were still able to show inhibition zones of bacterial growth. The antibacterial activity lasted up to 3 hours for amoxicillin, 24 hours for vancomycin, 8 days for cefamandole nafate and 8 months for rifampin.
Article
The purpose of this study is to clarify the main factor causing excellent blood compatibility of poly(2-methoxyethyl acrylate)(PMEA) by the comparison between PMEA and seven PMEA analogous polymers. The polymers have a typical functional group as ester side chains such as methoxyethyl, hydroxyethyl, phenoxyethyl, and alkyl groups. The properties of the polymers relating to water were investigated in terms of contact angle, equilibrium water content (EWC), and thermal analysis by differential scanning calorimetry. The water in PMEA could be classified into three types: nonfreezing water, freezing bound water, and free water while the water in the analogous polymers was classified into just two types: free and nonfreezing waters, regardless of the chemical structure of the side chain. The surface property represented by the contact angle of water corresponded to the content of the bound water (nonfreezing water + freezing bound water). The platelet compatibility in vitro did not depend on the contents of these waters, or on the contact angle. On the basis of the results of this work and the previous work on the platelet compatibility of poly(MEA-co-HEMA) (Tanaka et al. Biomacromolecules 2002;3;36-41), the main factor causing the excellent compatibility of PMEA is discussed.
Article
Abraxane (ABI-007) is a novel 130-nm, albumin-bound (nab) particle form of paclitaxel designed to utilize endogenous albumin pathways to increase intratumor concentrations of the active drug. This multicenter phase II study was designed to evaluate the efficacy and safety of Abraxane 260 mg/m2 every 3 weeks in patients with non-small-cell lung cancer (NSCLC). Patients with histologically confirmed, measurable NSCLC received Abraxane as first-line therapy. Forty-three patients were enrolled. The overall response rate was 16%; the disease control rate was 49%. Median time to progression was 6 months, and median survival was 11 months. The probability of not having progressed by 1 year was 13%; the probability of surviving 1 year was 45%. No severe hypersensitivity reactions were reported despite the lack of premedication; 95% of patients were treated without dose reduction. Two patients (5%) discontinued therapy because of treatment-related toxicities (neuropathy, fatigue [1 each]). No grade 4 treatment-related toxicity occurred. Abraxane 260 mg/m2 administered IV over 30 min without premedication was well tolerated. Significant tumor responses and prolonged disease control were documented in this group of patients with NSCLC. Exploration of higher doses of ABI-007 alone and in combination with other drugs active in NSCLC is warranted.
Article
Central venous catheters are a major cause of nosocomial bloodstream infections. Different attempts have been made to incorporate antimicrobial agents into catheters, particularly directed at the surface-coating of devices. To facilitate the antimicrobial adsorption, various cationic surfactants, which however showed several problems, have been used. On the other hand, impregnated catheters with only antimicrobials have demonstrated a short-term duration due to the difficulties to deliver the drug slowly. Thus, in order to obtain high antimicrobial-polymer affinity we synthesized or modified polyurethanes to introduce different functional groups. Polymers were loaded with two antibiotics, cefamandole nafate and rifampin (RIF), chosen for both their functional groups and their action spectrum. The in vitro release behavior showed that the elution of drugs depended on the matrix hydrophilicity and on the antibiotic-polymer and antibiotic-antibiotic interactions. To increase the amount of drug released, polyethylene glycol (PEG) used as a pore forming agent at different molecular weights was incorporated in the polymer bulk with antibiotics. As for the in vitro antimicrobial activity of matrices, assessed by Kirby-Bauer test, it was seen that antibiotics released from various formulations inhibited the bacterial growth and exerted a synergistic effect when both were present. In particular, PEG10000-containing polymer was active against the RIF-resistant S. aureus strain up to 23 days. These results suggest that the combined entrapping of antibiotics and pore formers in these novel polymer systems could be promising to prevent the bacterial colonization and to control the emergence of bacterial resistance.
Article
In a polymer-water matrix, freezable water is depressed due to either porosity confinement or interaction. The aim of the study was to examine water crystallization/melting depression by sub-ambient differential scanning calorimetry. The selected starch- and cellulose-based polymers including pre-gelatinized starch (PS), sodium alginate, sodium starch glycolate, hydroxypropylmethyl cellulose (HPMC), sodium carboxymethyl cellulose, and croscarmellose sodium were employed. The pre-treated with ambient humidity (85-100% relative humidity, at 30.0+/-0.2 degrees C for 10 days) and with excess water (hydrogels) samples were subjected to between 25 and -150 degrees C cooling-heating cycle at 5.00 degrees C/min rate. The volume fractions of hydrogels were measured by light scattering technique. It was observed that all polymers but PS and HPMC with ambient humidity presented freezable water in two distinct fractions namely bound water where crystallizing/melting temperature was depressed and bulk water. The water transition in samples with various contents exhibited the pattern as a polymer solution, thus rather than confinement, the depression was due to interaction. The volume fraction-melting temperature data derived from endotherms of hydrogels were successfully fitted to Flory's model (r(2): 0.934-0.999). The Flory's interaction parameters (chi(1)) were found to vary between 0.520 and 0.847. In addition, the smaller the value of chi(1), the larger melting was depressed, i.e., stronger affinity for water.
Der einfluß von quellungsmitteln auf das mechanische verhalten von polyurethane
  • Mitt
Mitt. Der einfluß von quellungsmitteln auf das mechanische verhalten von polyurethane. Makromol. Chem. 47, 72–85.
Caratterizzazione dinamo meccanica di un poliuretano carbossi-lato States of water in different hydrophilic polymers – DSC and FTIR studies
  • C Pacella
Pacella, C., 1999. Caratterizzazione dinamo meccanica di un poliuretano carbossi-lato. Master Thesis, Sapienza University of Rome, Rome, Italy, October. Ping, Z.H., Nguyen, Q.T., Chen, S.M., Zhou, J.Q., Ding, Y.D., 2001. States of water in different hydrophilic polymers – DSC and FTIR studies. Polymer 42, 8461–8467.