Preparation, characterization and surface study of poly-epsilon caprolactone magnetic microparticles

Magnetic microparticles (MMP) have shown to be applied in increasing applications in various fields of biotechnology and medicine. One of their most promising utilization is the magnetic resonance imaging (MRI) in which superparamagnetic substances as magnetite are used in a nanometric size (less than 30 nm) and encapsulated within locally injected biodegradable microparticles. In this paper, magnetite has been encapsulated in polymer-based microparticles. The MMP have been prepared by an emulsion evaporation method. The different parameters influencing the particles size were investigated. The size was found to decrease as the stirring speed or the stabilizer amount (to certain limit) increases. The encapsulation efficacy was more than 90% yielding a magnetite loading of up to 30%, w/w. The X-ray photoelectron spectroscopy (XPS) showed less than 2% of iron atoms at the microparticles surface. The zeta potential response of MMP towards pH variation was very similar to that of magnetite-free microparticles confirming the encapsulation of magnetite within the microparticles. X-ray diffraction assays showed that magnetite crystalline structure was conserved after emulsification and MMP formation. Vibration simple magnetometer (VSM) showed a superparamagnetic profile of the MMP with a magnetic saturation increasing with the increased magnetite amount in the microparticles. These magnetic microparticles can enable clinicians to control microparticles distribution after a local administration in tumors by MRI. They can also be administered to target a defined tumor area by focusing a magnetic field on the surfaces covering the cancerous tissue.     

Poly(PEGMA) magnetic nanogels: preparation via photochemical method,characterization and application as drug carrier

One-pot synthesis of magnetic nanogels with excellent biocompatibility via the photochemical method is reported in this paper. Poly(PEGMA) modified superparamagnetic nanogels (poly(PEGMA) magnetic nanogels) were synthesized by in-situ polymerization using poly(ethylene glycol) methacrylate (PEGMA) as the monomer and N, N′-methylene-bis-(acrylamide) (MBA) as the cross-linking agent in magnetite aqueous suspension under UV irradiation. The surface functional groups and components of magnetic nanogels were analyzed by Fourier transform infrared spectroscopy (FTIR) and a thermogravimetric analyzer (TGA). The results indicated that the poly(PEGMA) magnetic nanogels were synthesized successfully by coating poly(PEGMA) on the Fe₃O₄ nanoparticles under UV irradiation, and the Fe₃O₄ nanoparticles content in this nanogels was above 50 wt%. The morphology, size, zeta-potential and magnetic property were also characterized. The magnetic nanogels had a nearly spherical shape and core-shell structure, the average size in aqueous system measured by photon correlation spectroscopy (PCS) was 68.4 nm, which was much bigger than that in the dry state, the nanogels behaved superparamagnetically with saturated magnetization of 58.6 emu/g, and the zeta-potential was −16.3–−17.3 mV at physiological pH (6.8–7.4) which could help to maintain stability in blood. The preliminary application as drug carrier was made and the doxorubicin-loaded magnetic nanogels had an excellent property in slow-release. The experiment indicated that the magnetic nanogel was an ideal candidate carrier in target drug delivery systems and other biomedical application. Supported by the Natural Science Foundation of Shandong Province (Grant No. Q2006F01), Scientific and Technological Project of Shandong Province (Grant No. 2007GG3WZ02066) and Scientific and Technological Project of Department of Education, Shandong (Grant No. J07WC01)     

Preparation and characterization of emulsifier-free core–shell interpenetrating polymer network-fluorinated polyacrylate latex particles

The emulsifier-free core–shell interpenetrating polymer network (IPN) fluorinated polyacrylate latex particles with fluorine rich in shell were prepared by emulsifier-free seeded emulsion polymerization with water as the reaction medium. The fluorinated copolymer could be fixed on the particle surface due to the formation of interpenetrating polymer network. The resultant core–shell particles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS) analysis, Fourier transform infrared (FTIR) spectrometry, X-ray photoelectron spectroscopy (XPS) analysis and thermogravimetric analysis (TGA). The core–shell particles possessed very narrow monomodal particle size distributions. XPS analysis of the latex film displayed that perfluoroalkyl groups had the tendency to enrich at surface and there was a gradient concentration of fluorine in the structure of the latex film from the film–air interface to the film–glass interface. In addition, compared with the latex film of crosslinked polyacrylate prepared under the same condition, the emulsifier-free core–shell IPN-fluorinated polyacrylate latex film showed better thermal stability, higher contact angle and lower water uptake.     

Advanced design of t and pH dual‐responsive PDEAEMA–PVCL core–shell nanogels for siRNA delivery

The synthesis, characterization, and potential application as gene delivery systems of biodegradable dual‐responsive core–shell nanogels based on poly(2‐diethylaminoethyl) methacrylate (PDEAEMA) and poly(N‐vinylcaprolactam) (PVCL) are reported. These core–shell nanogels, having a PDEAEMA‐based core and a PVCL‐based shell, were synthesized by batch seeded emulsion polymerization. An indepth study of their swelling behavior was carried out, which presented a dual‐dependent thermo‐ and pH sensitivity. Core–shell nanogels synthesized formed complexes spontaneously through electrostatic interactions when mixing with small interfering RNA (siRNA) molecules. Moreover, the core–shell nanogel/siRNA complexes showed higher polyanion exchange resistance compared to that of the PDEAEMA‐based nanogel/siRNA complexes, indicating that the PVCL‐based shell enhanced the stability of the complexes. In vitro siRNA release profiles showed that siRNA release was controlled by the pH of the medium as well as by the crosslinking density of the PVCL‐based shell. These results indicate that dual‐responsive core–shell nanogels synthesized could be potentially useful as gene delivery systems. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3203–3217     

细胞内不同形态Gd基MRI造影剂的T1/T2弛豫性能及造影效果

将具有良好生物膜穿透性的异烟肼(INH)和Gd-DO3A偶联,合成了小分子MRI造影剂Gd-DO3A-INH;利用脉冲电转染技术标记间充质干细胞,有效提高了进入细胞的Gd-DO3A-INH浓度,并诱导部分游离态Gd-DO3A-INH在细胞质中自组装成纳米粒子。细胞样品的TEM观察到细胞内形成了Gd-DO3A-INH纳米粒子;细胞传代实验和体外MRI揭示了2种不同状态的Gd-DO3A-INH对细胞水质子弛豫速率的影响机制,以及细胞传代过程中细胞内2种不同状态Gd-DO3A-INH的浓度涨落引起的MRI造影效果的变化机制。     

Comparison of Five Conductivity Tensor Models and Image Reconstruction Methods Using MRI

Imaging of the electrical conductivity distribution inside the human body has been investigated for numerous clinical applications. The conductivity tensors of biological tissue have been obtained from water diffusion tensors by applying several models, which may not cover the entire phenomenon. Recently, a new conductivity tensor imaging (CTI) method was developed through a combination of B1 mapping, and multi-b diffusion weighted imaging. In this study, we compared the most recent CTI method with the four existing models of conductivity tensors reconstruction. Two conductivity phantoms were designed to evaluate the accuracy of the models. Applied to five human brains, the conductivity tensors using the four existing models and CTI were imaged and compared with the values from the literature. The conductivity image of the phantoms by the CTI method showed relative errors between 1.10% and 5.26%. The images by the four models using DTI could not measure the effects of different ion concentrations subsequently due to prior information of the mean conductivity values. The conductivity tensor images obtained from five human brains through the CTI method were comparable to previously reported literature values. The images by the four methods using DTI were highly correlated with the diffusion tensor images, showing a coefficient of determination (R2) value of 0.65 to 1.00. However, the images by the CTI method were less correlated with the diffusion tensor images and exhibited an averaged R2 value of 0.51. The CTI method could handle the effects of different ion concentrations as well as mobilities and extracellular volume fractions by collecting and processing additional B1 map data. It is necessary to select an application-specific model taking into account the pros and cons of each model. Future studies are essential to confirm the usefulness of these conductivity tensor imaging methods in clinical applications, such as tumor characterization, EEG source imaging, and treatment planning for electrical stimulation.     

Preparation and characterization of a magnetic microsphere synthesized from sucrose allyl ether for transcatheter arterial embolization

The polymerization of allyl monomers has been reported as notoriously difficult because of degradative chain transfer induced by the allyl radical as a primary radical with resonance-stabilized structure. A favorable approach is to produce polymers from inert monomers by using photodriven radical–mediated cyclization reaction (PRMC). In this study, Fe₃O₄ at sucrose allyl ether (Fe₃O₄@SAE) magnetic microspheres with sucrose as the skeleton and encapsulated nanomagnetic particles was prepared by PRMC. Its morphology and performance were characterized by using microscope, infrared, thermogravimetric and differential scanning calorimetry, scanning electron microscope/energy-dispersive spectrometer, and vibrating sample magnetometer. The feasibility as an embolic agent was evaluated by catheter transportability and cell compatibility. The results show that Fe₃O₄@SAE (sucrose allyl ether) magnetic microspheres have an average particle size of 371 μm, regular spherical shape, good dispersion, basically non-toxicity, and good cell compatibility. It has a certain degree of magnetism and can use alternating magnetic fields to achieve targeted embolization.     

Permanent Polymer Coating for in vivo MRI Visualization of Tissue Reinforcement Prostheses

The clinical advantage of MRI visualization of prostheses in soft tissue prolapses is very appealing as over 1 000 000 MRI‐transparent synthetic meshes are implanted annually, and postoperative complications such as mesh shrinkage and migration are frequent. Here, the synthesis of a new material composed of a DTPA‐Gd complex grafted onto a backbone of PMA via a covalent bond is described (DTPA‐Gd‐PMA). This new polymer is sprayed onto meshes and gives an MR signal for a long period without any significant release of Gd. In vitro cytocompatibility tests on fibroblasts show limited cytotoxicity. Microscopic investigations indicate that vital cells rapidly colonize the material. Finally, coated meshes implanted in rats are easily recognizable using an MR imaging system.

     

Preparation, characterization, and application of multistimuli-responsive microspheres with fluorescence-labeled magnetic cores and thermoresponsive shells

Novel functional microspheres with multistimuli-responsive properties have been prepared and characterized. The as-prepared microspheres respond to an external magnetic field, environmental temperature, and ultraviolet radiation. The in vitro drug-loading efficiency and drug-release behavior of these microspheres demonstrated that they could be used as drug carriers for drug controlled release. The results of in vivo distribution investigations of these microspheres showed that they exhibit a high magnetic-targeting effect, which holds promise for applications in various fields such as magnetic drug targeting and tissue labeling, among others.     

Preparation and characterization of magnetic bioadsorbent for adsorption of Cd(II) ions

A facile magnetic chitosan composite used for heavy metal ions removal was prepared. The adsorbents with large specific area and rich carboxyl groups exhibited good removal of Cd(II) ions and could be easily separated with magnetic separation. The adsorption capacity of Cd(II) was 48 ​mg ​g⁻¹ and the removal efficiency reached 86.7% after five cycles. Thus, the prepared magnetic chitosan composite could act as a potential adsorbent for Cd(II) ions removal.     

High-relaxivity magnetic resonance imaging (MRI) contrast agent based on supramolecular assembly between a gadolinium chelate, a modified dextran, and poly-beta-cyclodextrin

Nanosized contrast agents have great potential in magnetic resonance molecular imaging applications for clinical diagnosis. This study proposes new nanoparticles spontaneously formed under mild conditions and composed of a noncovalent adduct between a gadolinium complex, a polymer of beta-cyclodextrin (pbetaCD: MW 1.5 x 10(6) g mol(-1)) and a dextran grafted with alkyl chains (MD). The formation of this supramolecular nanoassembly is based upon a "lock-and-key" recognition process in which the hydrophobic alkyl chains of MD and the adamantyl moieties of macrocyclic Gd(III) chelates are included in the cavities of pbetaCD. The large number of betaCDs contained in the pbetaCD resulted in the formation of 200 nm diameter nanoparticles, each entrapping 1.8 x 10(5) molecules of a low-molecular-weight Gd complex. This system, which exhibits a great relaxivity enhancement (48.4 mM(-1) s(-1), at 20 MHz and 37 degrees C) compared to the Gd(III) chelate itself (5.2 mM(-1) s(-1)), appears to be a promising strategy for the in vivo targeted delivery of Gd(III) complexes. The mechanisms of particle formation, conjugation strategies, and relaxometric characterizations in the field of contrast-enhanced magnetic resonance imaging are discussed.     

Synthesis and relaxivity of polyamide paramagnetic metal complexes for magnetic resonance imaging

A new class of paramagnetic macromolecular magnetic resonance imaging contrast agents has been developed. Eight new polyamide ligands were synthesized by copolymerization of ethylenediaminetetraacetic acid dianhydride or diethylenetriaminepentaacetic acid dianhydride and diamine monomers. Their gadolinium(III), manganese(II) and iron(III) complexes were also synthesized. All polyamide ligands and metal complexes were characterized by ¹H nuclear magnetic resonance, infrared spectra and elemental analyses. Relaxivity studies showed that the polyamide paramagnetic metal complexes had obviously higher relaxation effectiveness as compared to corresponding simple monomeric paramagnetic metal complexes.     

Preparation and characterization of epoxy/SiO2 nanocomposites by cationic photopolymerization and sol–gel process

Epoxy/SiO₂ nanocomposite materials were prepared by cationic photopolymerization and sol–gel process using a novel epoxy oligomer (EP‐Si(OC₂H₅)₃) prepared by 3‐isocyanatopropyltriethoxysilane (IPTS)‐grafted bisphenol A epoxy resin and tetraethyl orthosilicate as inorganic precursor. The chemical structures of EP‐Si(OC₂H₅)₃ were characterized by Fourier transformed infrared spectroscopy. Transmission electron microscopy showed that the in situ generated nano‐SiO₂ dispersed uniformly in the EP matrix, and its average diameter is around 40 nm. The relationship between nanocomposite materials' thermal/mechanical properties and nano‐SiO₂ introduced were studied by thermogravimetric analysis, dynamic mechanical analysis, and impact strength test. The results showed that the nanocomposite materials' thermal and mechanical properties improved a lot with increase of the SiO₂ content. Copyright © 2013 John Wiley & Sons, Ltd.     

A statistical model for the heterogeneous structure of porous catalyst pellets

The complex structures of the void space of porous media are often characterised by parameters such as pore network connectivity and lattice size. This paper presents a comparison of the estimates of these parameters obtained from two previous methods based on nitrogen sorption and mercury porosimetry, and also from a new, completely independent approach based on pulsed-gradient spin-echo nuclear magnetic resonance (PGSE NMR). It was found that the new PGSE NMR technique obtains estimates of connectivity and lattice size in agreement with nitrogen sorption but different to mercury porosimetry. This difference was attributed to the various physical processes involved actually probing different aspects of the pore space geometry. It was further suggested that the representation of the pore structure derived from either nitrogen sorption or PGSE NMR is really a mapping of the real pore space onto an equivalent abstract, random pore bond network. However, it has been shown that this mapping does capture some of the characteristic properties of the pore space that control transport over mesoscopic ( < 10 microm) length scales. For materials which additionally possessed macroscopic (> 10 microm) structural heterogeneity, it was found that the model could also be adapted to predict the macroscopic transport properties of the porous medium.     

超声双重造影及MRI对胃癌诊断及术前T分期的对比研究

选取2017年8月~2019年2月我院收治的胃癌患者130例作为研究对象,依据患者病理诊断结果作为金标准,分析磁共振成像(magnetic resonance imaging,MRI)与超声双重造影对胃癌的诊断价值及术前T分期的价值。结果显示,超声双重造影共检出120例胃癌患者,出现10例漏诊,MRI共检出109例胃癌患者,出现21例漏诊。金标准共检出52例T1期、32例T2期、26例T3期、20例T4期患者,超声双重造影诊断出T1期48例,符合率92.31%;T2期30例,符合率93.75%;T3期24例,符合率92.31%;T4期18例,符合率90.00%,进一步分析显示,超声双重造影对不同胃癌T分期的诊断价值均高于MRI。因此,超声双重造影对胃癌的诊断价值及对术前T分期诊断价值均高于MRI。     

Magneto‐Optical Studies of HgTe/HgxCd1−xTe(S) Core–Shell Nanocrystals

The synthesis and magneto‐optical properties of HgTe nanocrystals capped with Hg_xCd_1?xTe(S) alloyed shells have been investigated. The magneto‐optical measurements included the use of optically detected magnetic resonance (ODMR) and circular polarized photoluminescence (CP‐PL) spectroscopy. The PL spectra suggest the existence of luminescence events from both the core HgTe and the Hg_xCd_1?xTe(S) shells. The continuous‐wave (cw) and time‐resolved ODMR measurements revealed that the luminescence at the shell regime is associated with a trap‐to‐band recombination emission. The electron trap is comprised of a Cd–Hg mixed site, confirming the existence of an alloyed Hg_xCd_1?xTe(S) composition. The ODMR data and the CP‐PL measurements together revealed the g‐values of the trapped electron and the valence band hole.     

Characterization of CNS disorders and evaluation of therapy using structural and functional MRI

Modern drug development requires technologies that allow rapid translation from the preclinical to the clinical stage. It is obvious that non-invasive imaging modalities such as magnetic resonance imaging (MRI) will play a central role in this regard. This article reviews the use of structural and functional MRI readouts for characterization of central nervous system (CNS) disorders and evaluation of the efficacy of potential CNS drugs. Examples comprise dementia of Alzheimer's type, cerebral ischemia, and neuroinflammation covering both clinical and preclinical aspects. In these examples MRI has been used to obtain relevant structural information on brain atrophy, on the location and extent of ischemic brain areas, and on the number and distribution of demyelinated plaques. These structural data are complemented by readouts assessing the functional consequences associated with the pathomorphological changes. In the last decade, MRI has evolved into a standard tool for the development of CNS drugs. With regard to target-specific/molecular imaging applications MRI is limited by its inherently low sensitivity; complementary imaging modalities utilizing optical and radionuclear reporter systems will thus be required.     

核壳结构的萘夫西林磁性分子印迹聚合物微球的制备及性能

以表面修饰双键的Fe₃O₄@SiO₂纳米颗粒为基体,以萘夫西林(nafcillin)为模板,甲基丙烯酸(MAA)为单体,乙二醇二甲基丙烯酸酯(EGDMA)为交联剂,偶氮二异丁腈(AIBN)为引发剂,采用三步升温聚合法合成了核壳结构的萘夫西林磁性分子印迹聚合物。采用傅里叶变换红外光谱仪(FT-IR)、透射电子显微镜(TEM)、X射线衍射仪(XRD)和振动样品磁强计(VSM)对制备的印迹聚合物微球进行了表征,得到的磁性印迹聚合物微球的粒径在320 nm左右,大小均匀,分散性较好,可以在外加磁场下与溶剂实现快速分离。对磁性印迹和非印迹聚合物进行了吸附性能研究,结果表明该印迹聚合物微球对模板分子具有很高的吸附容量(50.7 mg/g),特异性识别性能良好(印迹因子为2.46),有望应用于实际样品中萘夫西林残留量的富集分析。     

Synthesis,Relaxivity and MRI Enhancement of Linear Oligo‐Gd(III) Complexes with Poly (DTPA‐ester) Ligands Derived from Amino Acids

Six linear oligo‐DTPA‐ester Gd(III) complexes being used for potential MRI contrast agents were synthesized from amino adds and characterized. Their longitudinal relaxation rates were measured. One of them, die phenylalanine derivative, with high relaxivity, was chosen for the acute toxicity and T₁,‐weighted imaging test. The results indicated that there was no obvious toxicity for this new oligomeric Gd(III) complex, and it exhibits the highly enhanced MRI signal intensity and the increasing signal duration in the liver tissue compared to Gd‐DTPA.     

一类肝靶向含钆大环磁共振对比剂的设计、制备与性能表征

肝靶向磁共振对比剂有助于肝细胞癌的早期诊断, 目前临床使用的线性对比剂存在导致病人肾源性系统性纤维化和钆离子沉积的风险. 本工作设计制备了一类含有乙氧芳基或甲氧苯基亲脂性基团、以DOTA-酰肼(DOTA: 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid)为Gd³⁺离子螯合基团的大环类磁共振对比剂. 0.5 T磁场下测得其纵向弛豫率r₁值介于3.7~5.4 L•mmol^-1•s^-1, 优于临床使用对比剂Gd-DOTA, 弛豫率最高的为对比剂7h (Gd-DOTAH-EOPEI) (EOPEI: 1-(4-ethoxyphenyl)ethanimine), 略高于临床使用肝靶向对比剂Gd-EOB-DTPA (EOB: ethoxybenzyl; DTPA: diethylenetriaminepentaacetic acid), 比我们前期制得的肝靶向磁共振对比剂5d提高了约15%. 动物活体体内肝靶向磁共振成像研究显示, 所制备对比剂7b、7g和7h具有作为肝靶向磁共振对比剂的应用潜力. 结合弛豫率和活体体内成像数据, 筛选出了先导化合物7h.