Investigation on biological properties of tacrolimus-loaded poly(1,3-trimethylene carbonate) in vitro

The drug-eluting stents have been regarded as a milestone in inhibiting the restenosis of coronary arteries. However, adverse reactions caused by bare-metal stents and non-biodegradable polymer coatings may result in some clinical problems. In this study, a new tacrolimus-eluting stent coated with biodegradable poly(1,3-trimethylene carbonate) (PTMC) is developed. The structures are characterized by Fourier transform infrared (FTIR) analysis, and the wettability is measured by contact angle assay. The biological behaviors are evaluated by the in vitro platelets adhesion test, APTT test, the human umbilical cord artery smooth muscle cells (HUCASMCs), 4′,6-diamidine-2-phenylindole (DAPI) and actin immunofluorescence staining, MTT colorimetric assay. These results show that after blending tacrolimus into PTMC, the anticoagulant behavior is improved, and the adhesion and proliferation of HUCASMCs on samples are inhibited. This work aims to find one kind of surface erosion biodegradable polymers that can be applied as drug-eluting stent coatings.     

Molecular imaging of drug-eluting coronary stents: method development, optimization and selected applications

A molecular imaging application was developed to characterize the drug distribution on CYPHER? and NEVO? Drug-eluting Stents using MALDI Qq-ToF analytical methodology. The coating matrix, laser energy, laser frequency, spatial resolution (related to rastering speed) and mass spectrometer parameters were optimized to analyze drug distribution in both durable and biodegradable polymer matrices. The developed method was extended to generate data from stents explanted from porcine coronary arteries. Due to the method's intrinsic specificity, it offers a significant advantage over other techniques in that it allows low-level detection of the target molecule without biological interferences from the blood or tissue. The method is also capable of detecting drug-related degradation products both from the finished stent product and from explanted stents.     

A transferable non‐destructive method for the quantification of coronary stent coating components using Raman spectroscopy

Drug content of coronary stents is destructively evaluated using high pressure liquid chromatography. The method involves the dissolution of the coating from the stent into a solution and the analysis and quantification of the solvents' drug content. Quantification of the components of drug by Raman has been demonstrated with most recent methods using multivariate techniques. However, the calibration models generated as part of these methods are not easily transferable because they are developed using defined mixtures. In this work, we demonstrate a transferable non‐destructive Raman method for the evaluation and quantification of the drug coating components by developing a model from the pure samples of the coating constituents. Using the designed experiment, the transferable Raman method is equivalence tested with the standard high pressure liquid chromatography approach and compares favorably as a non‐destructive viable alternative. A method of dealing with the microheterogeneity of stent coatings is presented by spectral sample collection through the rotation of the stent. Knowledge of the coating formation and substrates is required in order to correctly interpret the results. Copyright © 2015 John Wiley & Sons, Ltd.     

Biodegradable nanocomposite magnetite stent for implant-assisted magnetic drug targeting

This study shows, for the first time, the fabrication of a biodegradable polymer nanocomposite magnetic stent and the feasibility of its use in implant-assisted-magnetic drug targeting (IA-MDT). The nanocomposite magnetic stent was made from PLGA, a biodegradable copolymer, and iron oxide nanopowder via melt mixing and extrusion into fibers. Degradation and dynamic mechanical thermal analyses showed that the addition of the iron oxide nanopowder increased the polymer’s glass transition temperature (T_g) and its modulus but had no notable effect on its degradation rate in PBS buffer solution. IA-MDT in vitro experiments were carried out with the nanocomposite magnetic fiber molded into a stent coil. These stent prototypes were used in the presence of a homogeneous magnetic field of 0.3 T to capture 100 nm magnetic drug carrier particles (MDCPs) from an aqueous solution. Increasing the amount of magnetite in the stent nanocomposite (0, 10 and 40 w/w%) resulted in an increase in the MDCP capture efficiency (CE). Reducing the MDCP concentrations (0.75 and 1.5 mg/mL) in the flowing fluid and increasing the fluid velocities (20 and 40 mL/min) both resulted in decrease in the MDCP CE. These results show that the particle capture performance of PLGA-based, magnetic nanocomposite stents are similar to those exhibited by a variety of different non-polymeric magnetic stent materials studied previously.     

Systemic Administration of Polymer‐Coated Nano‐Graphene to Deliver Drugs to Glioblastoma

Graphene—2D carbon—has received significant attention thanks to its electronic, thermal, and mechanical properties. Recently, nano‐graphene (nGr) has been investigated as a possible platform for biomedical applications. Here, a polymer‐coated nGr to deliver drugs to glioblastoma after systemic administration is reported. A biodegradable, biocompatible poly(lactide) (PLA) coating enables encapsulation and controlled release of the hydrophobic anticancer drug paclitaxel (PTX), and a hydrophilic poly(ethylene glycol) (PEG) shell increases the solubility of the nGr drug delivery system. Importantly, the polymer coating mediates the interaction of nGr with U‐138 glioblastoma cells and decreases cytotoxicity compared with pristine untreated nGr. PLA‐PEG‐coated nGr is also able to encapsulate PTX at 4.15 wt% and sustains prolonged PTX release for at least 19 d. PTX‐loaded nGr‐PLA‐PEGs are shown to kill up to 20% of U‐138 glioblastoma cells in vitro. Furthermore, nGr‐PLA‐PEG and CNT‐PLA‐PEG, two carbon nanomaterials with different shapes, are able to kill U‐138 in vitro as well as free PTX at significantly lower doses of drug. Finally, in vivo biodistribution of nGr‐PLA‐PEG shows accumulation of nGr in intracranial U‐138 glioblastoma xenografts and organs of the reticuloendothelial system.     

Novel insights into controlled drug release from coated pellets by confocal Raman microscopy

The development of novel therapeutics with improved efficacy implies increasing complexity of drug delivery systems, which in turn require advanced methods for their analytical characterization. Among these systems, pellets represent upcoming carrier systems, which show several advantages like simplified dosing and improved compliance among children and the aged population. However, rational development of such systems is hampered by the lack of non‐destructive, chemically selective analytical insight into compound distribution and drug release mechanisms. The aim of this study was to evaluate confocal Raman microscopy (CRM) for investigation of coated drug‐loaded pellets based on visualization of compound distribution and elucidation of drug release mechanisms. Three complementary approaches were applied for pellet characterization: analysis of cross sections after bisectioning, non‐invasive visualization of the pellet surface, and virtual cross sectioning in x–z direction. As the surface of such pellets is structured, a complementary approach of optical topography and CRM was applied for three‐dimensional analysis. Based on the individual Raman peak patterns, the drug and excipients forming the matrix of the pellets and the film coating were successfully visualized with high spatial resolution, verifying homogeneous drug distribution and intact polymer coating of the pellet. Further, analysis of the pellets after certain time intervals during drug release testing revealed pore formation in the polymer coating facilitating drug release and preceding drug depletion in the pellets matrix. CRM represents an upcoming technique for analytical characterization of carrier systems and elucidation of their complex drug release mechanisms, thus supporting rational development of novel therapeutics. Copyright © 2016 John Wiley & Sons, Ltd.     

南极海洋芳香烃低温降解微生物的拉曼光谱分析

激光镊子拉曼光谱技术可以实现在自然状态下对单个细胞或细胞器较长时间的观察研究.应用激光镊子拉曼光谱技术实时观察南极微生物低温降解芳香烃过程中单个南极细菌的细胞生长和胞内生物大分子的动态变化过程,收集、分析其拉曼光谱,结果发现:单细胞的拉曼光谱反映了其细胞内部的生命物质组成,南极动球菌 NJ41 和希瓦氏菌 NJ49 生...     

Laser transmission welding of poly(ethylene terephthalate) and biodegradable poly(ethylene terephthalate) – Based blends

Joining of Poly(Ethylene Terephthalate) PET and its biodegradable derivatives is of high relevance to ensure good productive rate, low cost and operational safety for fabrication of medical and electronic devices, sport equipments as well as for manufacturing of food and drug packaging solutions. In the present investigation, granules of PET and PETs modified by organic additives, which promote biodegradation of the polymeric chains, were prepared by extrusion compounding. The achieved granules were subsequently re-extruded to shape thin (330 μm) flat sheets. Substrates cut from these sheets were joined by Laser Transmission Welding (LTW) with a continuous wave High Power Diode Laser (cw-HPDL). First, based on a qualitative evaluation of the welded joints, the most suitable operational windows for PETs laser joining were identified. Second, characterization of the mechanical properties of the welded joints was performed by tensile tests. Accordingly, Young's modulus of PET and biodegradable PET blends was studied by Takayanagi's model and, based on the experimental results, a novel predicting analytical model derived from the mixture rule was developed. Lastly, material degradation of the polymeric joints was evaluated by FT-IR analysis, thus allowing to identify the main routes to thermal degradation of PET and, especially, of biodegradable PET blends during laser processing.     

SERS study on surface chain geometry of atactic poly (methyl methacrylate) film and nanosphere

The surface chain geometry of atactic poly (methyl methacrylate) (a‐PMMA) film and nanosphere (NS) was revealed by surface‐enhanced Raman scattering (SERS) spectra. The Ag nanoparticles and nanoplates were prepared by electrochemical deposition and chemical synthesis for SERS substrates. The experimental results suggested that the molecular chain axis of a‐PMMA film adopted a trans‐conformation on bonding to Ag surface ascribed to the short‐range chemical (CHEM) effect according to the SERS selection rules. However, for the well‐coated monolayer of a‐PMMA NSs, the α‐CH₃ in polymer chains stood vertically to the Ag surface due to the giant local electromagnetic effect, then the chain conformation presented in the interface between a‐PMMA NSs and Ag metal was adopted the opposite orientation compared with a‐PMMA film. The Raman enhancement of the Ag nanoparticles was more prominent than that of the Ag nanoplates due to the free energies of face‐centered cubic crystal faces in nanoparticles, but the single crystals with (111) plane of Ag nanoplates could improve the stability of SERS signals when the annealed temperature was above T_g of a‐PMMA NSs. The present work can provide some useful information of surface chain geometry and conformation of NSs for designing various materials with well‐defined structure via a‐PMMA NSs template. Copyright © 2013 John Wiley & Sons, Ltd.     

Use of atomic layer deposition to improve the stability of silver substrates for in situ,high‐temperature SERS measurements

A method to stabilize silver surface‐enhanced Raman spectroscopy (SERS) substrates for in situ, high‐temperature applications is demonstrated. Silver island films grown by thermal evaporation were coated with a thin layer (from 2.5 to 5 nm) of alumina by atomic layer deposition (ALD), which protects and stabilizes the SERS‐active substrate without eliminating the Raman enhancement. The temporal stability of the alumina‐coated silver island films was examined by measurement of the Raman intensity of rhodamine 6G molecules deposited onto bare and alumina‐coated silver substrates over the course of 34 days. The coated substrates showed almost no change in SERS enhancement, while the uncoated substrates exhibited a significant decrease in Raman intensity. To demonstrate the feasibility of the alumina‐coated silver substrate as a probe of adsorbates and reactions at elevated temperatures, an in situ SERS measurement of calcium nitrate tetrahydrate on bare and alumina‐coated silver was performed at temperatures ranging from 25 to 400 °C. ALD deposition of an ultrathin alumina layer significantly improved the thermal stability of the SERS substrate, thus enabling in situ detection of the dehydration of the calcium nitrate tetrahydrate at an elevated temperature. Despite some loss of Raman signal, the coated substrate exhibited greater thermal stability compared to the uncoated substrate. These experiments show that ALD can be used to synthesize stable SERS substrates capable of measuring adsorbates and processes at high temperature. Copyright © 2009 John Wiley & Sons, Ltd.     

Electrochemical functionalisation of SWNTs with poly(3,4‐ethylenedioxythiophene) evidenced by anti‐Stokes/Stokes Raman spectroscopy

The capability of anti‐Stokes/Stokes Raman spectroscopy to evaluate chemical interactions at the interface of a conducting polymer/carbon nanotubes is demonstrated. Electrochemical polymerisation of the monomer 3,4‐ethylenedioxythiophene (EDOT) on a Au support covered with a single‐walled carbon nanotube (SWNT) film immersed in a LiClO₄/CH₃CN solution was carried out. At the resonant optical excitation, which occurs when the energy of the exciting light coincides with the energy of an electronic transition, poly(3,4‐ethylenedioxythiophene) (PEDOT) deposited electrochemically as a thin film of nanometric thickness on a rough Au support presents an abnormally intense anti‐Stokes Raman spectrum. The additional increase in Raman intensity in the anti‐Stokes branch observed when PEDOT is deposited on SWNTs is interpreted as resulting from the excitation of plasmons in the metallic nanotubes. A covalent functionalisation of SWNTs with PEDOT both in un‐doped and doped states takes place when the electropolymerisation of EDOT, with stopping at +1.6 V versus Ag/Ag⁺, is performed on a SWNT film deposited on a Au plate. The presence of PEDOT covalently functionalised SWNTs is rationalised by (1) a downshift by a few wavenumbers of the polymer Raman line associated with the symmetric C C stretching mode and (2) an upshift of the radial breathing modes of SWNTs, both variations revealing an interaction between SWNTs and the conjugated polymer. Raman studies performed at different excitation wavelengths indicate that the resonant optical excitation is the key condition to observe the abnormal anti‐Stokes Raman effect. Copyright © 2010 John Wiley & Sons, Ltd.     

Study on the influence of advanced treatment processes on the surface properties of polylactic acid for a bio-based circular economy for plastics

New biotechnological processes using microorganisms and/or enzymes to convert carbonaceous resources, either biomass or depolymerized plastics into a broad range of different bioproducts are recognized for their high potential for reduced energy consumption and reduced GHG emissions. However, the hydrophobicity, high molecular weight, chemical and structural composition of most of them hinders their biodegradation. A solution to reduce the impact of non-biodegradable polymers spread in the environment would be to make them biodegradable. Different approaches are evaluated for enhancing their biodegradation. The aim of this work is to develop and optimize the ultrasonication (US) and UV photodegradation and their combination as well as dielectric barrier discharge (DBD) plasma as pre‐treatment technologies, which change surface properties and enhance the biodegradation of plastic by surface oxidation and thus helping bacteria to dock on them. Polylactic acid (PLA) has been chosen as a model polymer to investigate its surface degradation by US, UV, and DBD plasma using surface characterization methods like X-ray Photoelectron Spectroscopy (XPS) and Confocal Laser Microscopy (CLSM), Atomic Force Microscopy (AFM) as well as FT-IR and drop contour analysis. Both US and UV affect the surface properties substantially by eliminating the oxygen content of the polymer but in a different way, while plasma oxidizes the surface.     

Thiol‐modified gold‐coated glass as an efficient hydrophobic substrate for drop coating deposition Raman (DCDR) technique

In this paper we report an easy and low‐cost way to prepare a hydrophobic substrate for drop coating deposition Raman (DCDR) spectroscopy. This substrate is formed by a thiol‐modified Au‐coated glass and provides the Raman spectra with the same quality as the commercial Teflon‐coated stainless steel substrate (SpectRIM™, Tienta Sciences, Inc.) for model molecular systems – albumin solution and liposome suspension. Gold layer, similarly to polished steel in the commercial substrate, served as a highly refractive layer strongly increasing the Raman signal. The main advantage of introduced substrate is that it is simple and a low‐cost preparation easily manageable in every standard laboratory. Thus, it represents a promising alternative to commercial Teflon‐coated stainless steel substrate. Copyright © 2016 John Wiley & Sons, Ltd.     

Preparation of SERS active Ag nanoparticles encapsulated by phospholipids

A cost‐effective way of fabricating lipid‐coated surface‐enhanced Raman spectroscopy (SERS) substrate having reproducible high SERS activity was proposed. Ag nanoparticle embedded in 1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine (DOPC) and 1,2‐dioleoyl‐3‐trimethylammonium‐propane (DOTAP) membranes was produced by direct deposition of a 5‐nm‐thick layer of Ag onto the solid‐supported phospholipid membrane, and subsequent dissolution of the Ag nanoparticle‐embedded membrane in iso‐octane allowed easy one‐pot fabrication of DOPC‐ or DOTAP‐coated Ag nanoparticles. In particular, DOTAP produced nearly monodisperse lipid‐encapsulated Ag nanoparticles (9 nm in diameter) exhibiting reproducible high SERS activity (detecting up to 10 nM of rhodamine 6G and 0.5 μM of glutathione). In addition, the process was modified to incorporate variety of Raman active molecules (rhodamine 6G, malachite green, 4‐aminothiopheonol, 4‐mercaptopyridine) into the particle‐encapsulating lipid bilayer. The DOTAP/Raman dye‐coated Ag nanoparticles also generated high SERS activity to enable potential application of the DOTAP/Raman dye‐coated Ag nanoparticles feasible in different areas. Copyright © 2014 John Wiley & Sons, Ltd.     

Quantitative ToF-SIMS studies of protein drug release from biodegradable polymer drug delivery membranes

Biodegradable polymers are of interest in developing strategies to control protein drug delivery. The protein that was used in this study is Keratinocyte Growth Factor (KGF) which is a protein involved in the re-epithelialization process. The protein is stabilized in the biodegradable polymer matrix during formulation and over the course of polymer degradation with the use of an ionic surfactant Aerosol-OT (AOT) which will encapsulate the protein in an aqueous environment. The release kinetics of the protein from the surface of these materials requires precise timing which is a crucial factor in the efficacy of this drug delivery system.Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used in the same capacity to identify the molecular ion peak of the surfactant and polymer and use this to determine surface concentration. In the polymer matrix, the surfactant molecular ion peak was observed in the positive and negative mode at m/z 467 and 421, respectively. These peaks were determined to be [AOT + Na⁺] and [AOT − Na⁺]. These methods are used to identify the surfactant and protein from the polymer matrix and are used to measure the rate of surface accumulation. The second step was to compare this accumulation rate with the release rate of the protein into an aqueous solution during the degradation of the biodegradable film. This rate is compared to that from fluorescence spectroscopy measurements using the protein autofluorescence from that released into aqueous solution [C.M. Mahoney, J. Yu, A. Fahey, J.A.J. Gardella, SIMS depth profiling of polymer blends with protein based drugs, Appl. Surf. Sci. 252 (2006), 6609-6614.].     

Raman micro‐spectroscopy for quantitative thickness measurement of nanometer thin polymer films

The sensitivity of far‐field Raman micro‐spectroscopy was investigated to determine quantitatively the actual thickness of organic thin films. It is shown that the thickness of organic films can be quantitatively determined down to 3 nm with an error margin of 20% and down to 1.5 nm with an error margin of 100%. Raman imaging of thin‐film surfaces with a far‐field optical microscope establishes the distribution of a polymer with a lateral resolution of ~400 nm and the homogeneity of the film. Raman images are presented for spin‐coated thin films of polysulfone (PSU) with average thicknesses between 3 and 50 nm. In films with an average thickness of 43 nm, the variation in thickness was around 5% for PSU. In films with an average thickness of 3 nm for PSU, the detected thickness variation was 100%. Raman imaging was performed in minutes for a surface area of 900 µm². The results illustrate the ability of far‐field Raman microscopy as a sensitive method to quantitatively determine the thickness of thin films down to the nanometer range. Copyright © 2015 John Wiley & Sons, Ltd.     

运用表面增强拉曼散射(SERS)和密度泛函数理论(DFT)模拟计算研究对硝基苯胺在金纳米颗粒表面吸附行为

在沉积金纳米颗粒的干燥滤纸上进行对硝基苯胺的表面增强拉曼散射(SERS)光谱研究,并与对硝基苯胺在金胶水溶液中的表面增强拉曼散射(SERS)光谱相比,分子拉曼光谱发生了很大变化。同时利用DFT理论计算对硝基苯胺在金胶颗粒上的吸附行为的拉曼光谱。DFT理论模拟计算和FI-Raman实验分析都表明这种变化源于对硝基苯胺的不同吸附方式。SERS和DFT结合研究分子的吸附是一种有效的技术。     

Polymer Characterization by Raman Spectroscopy

Abstract

Although the Raman spectrum of polystyrene was measured as long ago as 1932 [1]. and the value of vibrational spectroscopy for the characterization of polymer structures became evident a few years later. Raman spectroscopy failed to make a significant impact in the field for many years. Indeed. in 1964 [2]. Nielsen commented that while infrared spectroscopy had yielded a great deal of information about the molecular and crystalline structure of high polymers. Raman spectroscopy had not been widely used or been very helpful in the investigation of polymers. He went on to note that the main reason for this state of affairs was that it had generally been quite difficult to obtain their Raman spectra but. nevertheless. efforts to overcome the difficulties facing the Raman spectroscopy of polymers would be very worthwhile.     

Simple process for fabricating a monolithic polymer optical waveguide

A simple and economical fabrication process for a monolithic polymer optical waveguide in which different materials are serially grafted is proposed and demonstrated. A cladding layer with a waveguide core groove is fabricated by microtransfer molding. An epoxy resin solution is spin coated onto the cladding before selective photoexposure to form a transparent waveguide core. An optical functional polymer solution is then spin coated to form a serially grafted waveguide structure. Thus two types of polymer fill the groove to realize a monolithically integrated waveguide. Controlling the groove shape results in a flat surface. A low connection loss between the two polymers, less than 0.01 dB/point, is obtained.