Publications

2009
Levy Y, Mandler D, Weinberger J, Domb AJ. Evaluation of Drug-Eluting Stents' Coating Durability-Clinical and Regulatory Implications. JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS. 2009;91B (1) :441-451.
Eldan M, Shoham T, Erel Y, Mandler D. Monitoring Heavy Metals in Seawater by Their Electrochemically Induced Deposition as Hydroxides. ELECTROANALYSIS. 2009;21 (3-5) :368-378.
Noyhouzer T, Kohen R, Mandler D. A new approach for measuring the redox state and redox capacity in milk. ANALYTICAL METHODS. 2009;1 (2) :93-99.
Shaulov Y, Okner R, Levi Y, Tal N, Gutkin V, Mandler D, Domb AJ. Poly(methyl methacrylate) Grafting onto Stainless Steel Surfaces: Application to Drug-Eluting Stents. ACS APPLIED MATERIALS & INTERFACES. 2009;1 (11) :2519-2528.
Okner R, Oron M, Tal N, Nyska A, Kumar N, Mandler D, Domb AJ. Electrocoating of stainless steel coronary stents for extended release of paclitaxel. J Biomed Mater Res AJournal of biomedical materials research. Part A. 2009;88 (2) :427 - 36.Abstract
Nonbiodegradable polymer coating based on N-(2-carboxyethyl)pyrrole (PPA) and butyl ester of PPA (BuOPy) were successfully electrodeposited on a stainless steel stent surface using cyclic voltammetry. Chemical composition of the coating was examined by X-ray photoelectron spectroscopy. Polymer stability was examined by immersing the coated stent into 1:1 solution of fetal calf serum:seline solution up to 1 year and implantation subcutaneously in mouse for 1 week. Morphology changes were then recorded by scanning electron microscopy. Paclitaxel loading was carried out by immersion into drug solution and its release was detected by HPLC. The results show that thin (single micrometers), uniform coating with various morphology and hydrophobicity can be created by electrochemical deposition. The polymer did not show significant histopathological or morphological changes in vitro and in vivo. The surface properties allow loading appropriate amounts of paclitaxel and release it slowly up to a month.[on SciFinder (R)]
Levy Y, Mandler D, Weinberger J, Domb AJ. Evaluation of drug-eluting stents' coating durability--clinical and regulatory implications. J Biomed Mater Res B Appl BiomaterJournal of biomedical materials research. Part B, Applied biomaterials. 2009;91 (1) :441 - 51.Abstract
Drug-eluting stents (DES) revolutionized cardiovascular treatment by virtually eliminating in-stent restanosis. However, in the past 3 years the U.S. Food and Drug Administration and published studies have raised several safety issues regarding DES such as late state thrombosis and increased mortality. Recent publications have described DES coating delaminating, cracking, and peeling in commercially available stents. It has been suggested that these properties are responsible for the deleterious effects. The goal of this work is to describe a quantitative in vitro durability tests for DES, referred to as Quantified Defects (QD). The technique was implemented on various stent polymer-coated models to determine its ability to differentiate between coating properties. Stents' coating defects were tested using light microscopy, scanning electron microscopy, and a micro-balance. High-performance liquid chromatography was used for measuring drug release. Stents were incubated at either 37 or 60 degrees C and sampled at 0, 3, and 30 days. Stent coating durability was tested using stainless steel control stents versus stents having increased surface adhesion, both of which were then coated with conventional spray-coating methods. Drug-coated stents tested for defects demonstrated a deteriorating durability profile as reflected by QD indices. Different coating models showed unique QD indices that reflected their superior or inferior coating durability. These results indicated that the methodology was able to differentiate between different models. In conclusion, this simple low-cost testing methodology can be easily used during DES development, with either durable or biodegradable polymers.[on SciFinder (R)]
Zhang J, Burt DP, Whitworth AL, Mandler D, Unwin PR. Polyaniline Langmuir-Blodgett films: formation and properties. Phys Chem Chem PhysPhysical chemistry chemical physics : PCCP. 2009;11 (18) :3490 - 6.Abstract
The deposition and characterisation of Langmuir-Blodgett (LB) layers of polyaniline (PAN) on solid supports is described. Langmuir films were spread as a mixture of PAN and dodecylbenzenesulfonic acid (DBSA) at the water/air interface and deposited on either glass or indium tin oxide (ITO). Mono- and multi-layer films of PAN/DBSA were characterized by X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), absorption spectroscopy and cyclic voltammetry (CV). The ultrathin films produced were found to be highly uniform and very stable. Further characterisation of the films was accomplished by scanning electrochemical microscopy (SECM) in the feedback mode. It was found that the conductivity depended strongly on the pH of the solution and the number of layers deposited. Values for the pH-dependent lateral conductivity of PAN LB films are reported.[on SciFinder (R)]
Levy Y, Tal N, Tzemach G, Weinberger J, Domb AJ, Mandler D. Drug-eluting stent with improved durability and controllability properties, obtained via electrocoated adhesive promotion layer. J Biomed Mater Res B Appl BiomaterJournal of biomedical materials research. Part B, Applied biomaterials. 2009;91 (2) :819 - 30.Abstract
Drug-eluting stents (DES) have become an accepted technology in intravascular intervention. Manufacturing methodologies of DES are based mainly on mechanical processes, which tend to generate coatings that have poor stability properties; these were recently related as a potential hazard. A novel approach for significantly increasing the adhesion of polymer coatings onto DES is presented. The method is based on the electrochemistry of diazonium salts. These substances are organic compounds with the characteristic structure of R-N(2) (+) X(-), where R is an organic residue and X(-) is an anion. The objective of this article is to study the properties of a selected diazonium salt 4-(1-dodecyloxy)-phenyldiazonium tetrafluoroborate, referred as C(12)-phenyldiazonium. This material was found to be a superior adhesive promoter for polymeric coatings applied onto metallic stents. C(12)-phenyldiazonium was synthesized and electrocoated on metallic stents and plates. The multilayer films of C(12)-phenyldiazonium were further characterized through electrochemical (cyclic voltammetry, impedance spectroscopy), physical (light and scanning electron microscopy, X-ray photoelectron spectroscopy, peeling tests), and chemical methodology (high pressure liquid chromatography). Further biocompatibility properties of the electrocoated basecoat were evaluated using in vitro and in vivo models. Synthesized C(12)-phenyldiazonium was successfully electrocoated onto metallic surfaces. Electrochemical tests demonstrated its efficient and controllable electrocoating. C(12)-phenyldiazonium was found to increase polymeric coating stability as was reflected by a standard adhesion test. Electrocoated metallic stents spray-coated with a second polymeric film showed improved durability following incubation in physiological buffer. Furthermore, this improvement in durability exhibits stabilized drug release. In addition, biocompatibility evaluations have demonstrated basecoat's inert properties.[on SciFinder (R)]
Becker A, Tobias H, Mandler D. Electrochemical determination of uranyl ions using a self-assembled monolayer. Anal ChemAnalytical chemistry. 2009;81 (20) :8627 - 31.Abstract
Uranyl, UO(2)(2+), was electrochemically determined by a phosphate based self-assembled monolayer. A pretreated gold electrode with 2-mercatpoethanol was chemically modified by POCl(3) or POBr(3) to obtain the surface phosphate active sites. The different stages were characterized by reflection-absorption Fourier transform-infrared (FT-IR) spectroscopy, capacity, and X-ray photoelectron spectroscopy (XPS). The electrochemical determination of UO(2)(2+) was accomplished, after preconcentration under open circuit potential, by square wave voltammetry.[on SciFinder (R)]
Okner R, Shaulov Y, Tal N, Favaro G, Domb AJ, Mandler D. Electropolymerized tricopolymer based on N-pyrrole derivatives as a primer coating for improving the performance of a drug-eluting stent. ACS Appl Mater InterfacesACS applied materials & interfaces. 2009;1 (4) :758 - 67.Abstract
The coating of medical implants by polymeric films aims at increasing their biocompatibility as well as providing a durable matrix for the controlled release of a drug. In many cases, the coating is divided into a primer layer, which bridges between the medical implant and the drug-eluting matrix. The primer coating must be very carefully designed in order to provide optimal interactions with the surface of the medical implant and the outer layer. Here we present a simple and versatile approach for designing the primer layer based on electropolymerization of a carefully chosen blend of three different pyrrole derivatives: N-methylpyrrole (N-me), N-(2-carboxyethyl)pyrrole (PPA), and the butyl ester of N-(2-carboxyethyl)pyrrole (BuOPy). The composition and physical properties of the primer layer were studied in detail by atomic force microscopy (AFM) and a nano scratch tester. The latter provides the in-depth analysis of the adhesion and viscoelasticity of the coating. AFM phase imaging reveals a uniform distribution of the three monomers forming rough morphology. This primer layer significantly improved the morphology, stability, and paclitaxel release profile of a paclitaxel-eluting matrix based on methyl and lauryl methacrylates.[on SciFinder (R)]
Shaulov Y, Okner R, Levi Y, Tal N, Gutkin V, Mandler D, Domb AJ. Poly(methyl methacrylate) grafting onto stainless steel surfaces: application to drug-eluting stents. ACS Appl Mater InterfacesACS applied materials & interfaces. 2009;1 (11) :2519 - 28.Abstract
Drug-eluting stents (DESs) have been associated with adverse clinical effects. Moreover, recent publications have shown that the coating of DESs suffers from defects. The purpose of this contribution is to examine a three-step process for surface modification as a means of improving the durability of DESs. In the first step, 4-(2-bromoethyl)benzenediazonium tetrafluoroborate was electrografted onto a stainless steel (SS) stent. X-ray photoelectron spectroscopy (XPS) of the modified stent confirmed the formation of the organic layer. In the second step, methyl methacrylate was polymerized onto the grafted surface by atom-transfer radical polymerization. XPS, electrochemical impedance spectroscopy, and contact-angle measurements were used to characterize the polymer brushes. The last step involved spray-coating of the stent with a drug-in-polymer matrix [poly(n-butyl methacrylate)/poly(ethylene-co-vinyl acetate) + paclitaxel]. Scanning electron microscopy confirmed the considerably improved durability of the drug-in-polymer matrix. Bare controls showed greater cracking and delamination of the coating than did the two-step modified stents after incubation under physiological (37 degrees C) and accelerated (60 degrees C) conditions. Finally, paclitaxel controlled release from the modified SS DESs was moderate compared with that of nontreated samples. In conclusion, the proposed method significantly improves the durability of drug-in-polymer matrixes on a SS DESs.[on SciFinder (R)]
Sheffer M, Mandler D. Control of locally deposited gold nanoparticle on polyaniline films. Electrochim. ActaElectrochimica Acta. 2009;54 (11) :2951 - 2956.Abstract
Local and bulk deposition of Au particles was accomplished by the spontaneous reaction between chem. reduced polyaniline (PAN) thin films and AuCl4- ions. PAN layers were electrodeposited on glassy C (GC). Characterization of the PAN films was carried out by microscopy and electrochem. Local deposition of Au particles was performed by scanning electrochem. microscopy, where a Au microelectrode was used to produce a flux of Au ions in close vicinity to an unbiased PAN film. The nature of the Au particles was greatly affected by the potential applied at the microelectrode as well as the oxidn. state of the PAN films. [on SciFinder(R)]
Okner R, Shaulov Y, Tal N, Favaro G, Domb AJ, Mandler D. Electropolymerized Tricopolymer Based on N-Pyrrole Derivatives as a Primer Coating for Improving the Performance of a Drug-Eluting Stent. ACS Appl. Mater. InterfacesACS Applied Materials & Interfaces. 2009;1 (4) :758 - 767.Abstract
The coating of medical implants by polymeric films aims at increasing their biocompatibility as well as providing a durable matrix for the controlled release of a drug. In many cases, the coating is divided into a primer layer, which bridges between the medical implant and the drug-eluting matrix. The primer coating must be very carefully designed in order to provide optimal interactions with the surface of the medical implant and the outer layer. Here we present a simple and versatile approach for designing the primer layer based on electropolymn. of a carefully chosen blend of three different pyrrole derivs.: N-methylpyrrole (N-me), N-(2-carboxyethyl)pyrrole (PPA), and the Bu ester of N-(2-carboxyethyl)pyrrole (BuOPy). The compn. and phys. properties of the primer layer were studied in detail by at. force microscopy (AFM) and a nano scratch tester. The latter provides the in-depth anal. of the adhesion and viscoelasticity of the coating. AFM phase imaging reveals a uniform distribution of the three monomers forming rough morphol. This primer layer significantly improved the morphol., stability, and paclitaxel release profile of a paclitaxel-eluting matrix based on Me and lauryl methacrylates. [on SciFinder(R)]
Levy Y, Tal N, Tzemach G, Weinberger J, Domb AJ, Mandler D. Drug-eluting stent with improved durability and controllability properties, obtained via electrocoated adhesive promotion layer. J. Biomed. Mater. Res., Part BJournal of Biomedical Materials Research, Part B: Applied Biomaterials. 2009;91B (2) :819 - 830.Abstract
Drug-eluting stents (DES) have become an accepted technol. in intravascular intervention. Manufg. methodologies of DES are based mainly on mech. processes, which tend to generate coatings that have poor stability properties; these were recently related as a potential hazard. A novel approach for significantly increasing the adhesion of polymer coatings onto DES is presented. The method is based on the electrochem. of diazonium salts. These substances are org. compds. with the characteristic structure of R-N X-, where R is an org. residue and X- is an anion. The objective of this article is to study the properties of a selected diazonium salt 4-(1-dodecyloxy)-phenyldiazonium tetrafluoroborate, referred as C12-phenyldiazonium. This material was found to be a superior adhesive promoter for polymeric coatings applied onto metallic stents. C12-phenyldiazonium was synthesized and electrocoated on metallic stents and plates. The multilayer films of C12-phenyldiazonium were further characterized through electrochem. (cyclic voltammetry, impedance spectroscopy), phys. (light and SEM, XPS, peeling tests), and chem. methodol. (high pressure liq. chromatog.). Further biocompatibility properties of the electrocoated basecoat were evaluated using in vitro and in vivo models. Synthesized C12-phenyldiazonium was successfully electrocoated onto metallic surfaces. Electrochem. tests demonstrated its efficient and controllable electrocoating. C12-phenyldiazonium was found to increase polymeric coating stability as was reflected by a std. adhesion test. Electrocoated metallic stents spray-coated with a second polymeric film showed improved durability following incubation in physiol. buffer. Furthermore, this improvement in durability exhibits stabilized drug release. In addn., biocompatibility evaluations have demonstrated basecoat's inert properties. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009. [on SciFinder(R)]
Becker A, Tobias H, Mandler D. Electrochemical Determination of Uranyl Ions Using a Self-Assembled Monolayer. Anal. Chem. (Washington, DC, U. S.)Analytical Chemistry (Washington, DC, United States). 2009;81 (20) :8627 - 8631.Abstract
Uranyl, UO22+, was electrochem. detd. by a phosphate based self-assembled monolayer. A pretreated Au electrode with 2-mercatpoethanol was chem. modified by POCl3 or POBr3 to obtain the surface phosphate active sites. The different stages were characterized by reflection-absorption FTIR spectroscopy, capacity, and XPS. The electrochem. detn. of UO22+ was accomplished, after preconcn. under open circuit potential, by square wave voltammetry. [on SciFinder(R)]
Okner R, Domb AJ, Mandler D. Electrochemically deposited poly(ethylene glycol)-based sol-gel thin films on stainless steel stents. New J. Chem.New Journal of Chemistry. 2009;33 (7) :1596 - 1604.Abstract
Poly(ethylene glycol) (PEG) was modified with 3-isocyanatopropyltriethoxysilane (IPTS) to obtain PEG-disilane. This monomer was electrochem. polymd. and deposited onto a stainless steel surface to form a thin PEGylated sol-gel film. The monomer was characterized by 1H-NMR and FTIR spectroscopy. The sol-gel film was characterized by absorption-reflection IR spectroscopy (AR-FTIR), energy dispersive X-ray anal. (EDX), cyclic voltammetry (CV), profilometry, SEM and potentiodynamic polarization. AR-FTIR confirmed the formation of a polymer, while the stability of the polymeric film on stainless steel in buffer phosphate was studied by SEM. The polymer was successfully electrodeposited onto 316L coronary stents. Its flexibility was examd. by dilating the coated stents and inspecting it by SEM. The hydrophilic, smooth PEGylated sol-gel coating significantly reduced the activation and adhesion of platelets as compared with the bare stainless steel surface. This coating, which can be applied to complex geometries, such as stents, is likely to serve as an excellent biomaterial. [on SciFinder(R)]
Levy Y, Mandler D, Weinberger J, Domb AJ. Evaluation of drug-eluting stents' coating durability-Clinical and regulatory implications. J. Biomed. Mater. Res., Part BJournal of Biomedical Materials Research, Part B: Applied Biomaterials. 2009;91B (1) :441 - 451.Abstract
Drug-eluting stents (DES) revolutionized cardiovascular treatment by virtually eliminating in-stent restenosis. However, in the past 3 years the U.S. Food and Drug Administration and published studies have raised several safety issues regarding DES such as late state thrombosis and increased mortality. Recent publications have described DES coating delaminating, cracking, and peeling in com. available stents. It has been suggested that these properties are responsible for the deleterious effects. The goal of this work is to describe a quant. in vitro durability tests for DES, referred to as Quantified Defects (QD). The technique was implemented on various stent polymer-coated models to det. its ability to differentiate between coating properties. Stents' coating defects were tested using light microscopy, SEM, and a micro-balance. High-performance liq. chromatog. was used for measuring drug release. Stents were incubated at either 37° or 60° and sampled at 0, 3, and 30 days. Stent coating durability was tested using stainless steel control stents vs. stents having increased surface adhesion, both of which were then coated with conventional spray-coating methods. Drug-coated stents tested for defects demonstrated a deteriorating durability profile as reflected by QD indexes. Different coating models showed unique QD indexes that reflected their superior or inferior coating durability. These results indicated that the methodol. was able to differentiate between different models. In conclusion, this simple low-cost testing methodol. can be easily used during DES development, with either durable or biodegradable polymers. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009. [on SciFinder(R)]
Eldan M, Shoham T, Erel Y, Mandler D. Monitoring heavy metals in seawater by their electrochemically induced deposition as hydroxides. ElectroanalysisElectroanalysis. 2009;21 (3-5) :368 - 378.Abstract
A novel method for monitoring heavy metals in seawater is presented. The method is based on the electrochem. codeposition of metal hydroxides driven by the change of pH at the surface of a gold electrode. Altering the pH is achieved by applying a neg. potential or current that reduces the water and thereby increases the concn. of hydroxyl ions. This, in turn, causes metals to coppt. with Mg(OH)2. The continuous deposition enriches the ppt. with the metals (as compared with their concn. in the aq. phase) and allows their detn. by ICP-MS upon dissolving the deposit. A set of expts. in which seawater was spiked with 1-10 ppm of Cu, Cr, Co, Zn and Pb, was conducted. It was obsd. that metals were accumulated in the ppt. as a function of time and their concn. in seawater. The ppts. were analyzed by SEM, EDS and XPS indicating that the metal hydroxides formed a sep. phase from Mg(OH)2 and even water electroreducible metals, e.g., Cu2+, preferentially pptd. as hydroxides. Distribution consts. correlating the concns. of the metals in the deposited salts to their concns. in seawater were calcd. These calcns. imply that the mechanism governing the pptn. of the metal hydroxides by the electrochem. induced process is likely to be kinetically and mass-transport driven rather than thermodynamically controlled. [on SciFinder(R)]
Noyhouzer T, Kohen R, Mandler D. A new approach for measuring the redox state and redox capacity in milk. Anal. MethodsAnalytical Methods [Internet]. 2009;1 (2) :93 - 99. Publisher's VersionAbstract
Milk is one of the most fundamental ingredients in our diet. It is a complex biol. fluid, which contains numerous substances, ranging from metal ions to enzymes. There is a const. search for an improved way of monitoring its quality and freshness. These are highly affected by the redox state of milk, which is governed by different species. In this study, we investigated the redox state and capacity of milk. Specifically, milk was potentiometrically titrated using different redox mediators, which enabled facilitation of electron transfer between different oxidizable species and the electrode. We found that the iodine/iodide redox couple was superior for measuring the redox capacity of milk. These measurements revealed that milk is not a well-poised system due to the presence of at least two different oxidizable species, one of which is hydrophobic while the other is hydrophilic and therefore could be sepd. by phase sepn. of milk. [on SciFinder(R)]
Zhang J, Burt DP, Whitworth AL, Mandler D, Unwin PR. Polyaniline Langmuir-Blodgett films: formation and properties. Phys. Chem. Chem. Phys.Physical Chemistry Chemical Physics. 2009;11 (18) :3490 - 3496.Abstract
The deposition and characterization of Langmuir-Blodgett (LB) layers of polyaniline (PAN) on solid supports is described. Langmuir films were spread as a mixt. of PAN and dodecylbenzenesulfonic acid (DBSA) at the water/air interface and deposited on either glass or indium tin oxide (ITO). Mono- and multi-layer films of PAN/DBSA were characterized by XPS, at. force microscopy (AFM), absorption spectroscopy and cyclic voltammetry (CV). The ultrathin films produced are highly uniform and very stable. Further characterization of the films was accomplished by scanning electrochem. microscopy (SECM) in the feedback mode. The cond. depended strongly on the pH of the soln. and the no. of layers deposited. Values for the pH-dependent lateral cond. of PAN LB films are reported. [on SciFinder(R)]

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