One‐Step Formulation of Protein Microparticles with Tailored Properties: Hard Templating at Soft Conditions

Formulation of therapeutic proteins into particulate forms is a main strategy for site‐specific and prolonged protein delivery as well as for protection against degradation. Precise control over protein particle size, dispersity, purity, as well as mild preparation conditions and minimal processing steps are highly desirable. It is, however, hard to fit all these criteria with conventional preparation techniques. Here a one‐step hard‐templating synthesis of microparticles composed of functional, non‐denatured protein is reported. The method is based on filling porous CaCO₃ microtemplates with the protein near to its isoelectric point (pI) followed by pH‐ or EDTA‐mediated dissolution of the tempplates. In principle, a wide variety of proteins can be converted into microparticles using this approach. The main requirement is an overlap of the protein insolubility and a template solubility for a certain parameter (here pH or EDTA). Here the formulation of insulin particles is studied in detail and it is shown that particles consisting of high molecular weight protein (catalase) can also be prepared. In this context, the synthesis of CaCO₃ templates with controlled size, the mechanism of the protein microparticle formation and mechanical properties of the microparticles are discussed. For the first time, the fabrication of mesoporous monodispersed CaCO₃ microtemplates with identical porocity but tuned diameter from 3 to 20 μm is demonstrated. The protein particle diameter can be adjusted by choosing the appropriate template size that is critical for successful pulmonary delivery of insulin. As a first step towards insulin delivery, the in vitro release of insulin at physiological conditions is studied.     

Surface treatment of CaCO3 with a mixture of amino- and mercapto-functional silane coupling agents and tensile properties of the rubber composites

In order to reinforce the composite consisting of isoprene rubber (IR) and calcium carbonate (CaCO₃) particles, the surface treatment of CaCO₃ particles with a mixture of amino- and mercapto-functional silane coupling agents was investigated. The quantity of chemisorbed silanes in treated CaCO₃ measured using thermogravimetry was greater for amino- than for mercapto-silane and for the tri- than for the dialkoxy structure. Second, the molecular mobility of polycondensate of the mixtures with the trialkoxy structure measured using ¹H pulse nuclear magnetic resonance had the least molecular mobility, i.e., formed the highest density network. The greater values of stress at 500% strain, fracture stress, and elongation at break were determined for the treatment with amino- and mercapto-functional silanes having a trialkoxy structure from the stress-strain curves of composite. The mixture treatment with dialkoxy structure and with amino- or mercapto-functional silane only did not improve the mechanical properties sufficiently. Interactions between the amino group and the CaCO₃ surface, covalent bonding between the mercapto group and the IR, and high density network formation of trialkoxy silane were important for improving the mechanical properties of the composite.     

Nuklearpharmaka — Ihre Entwicklung,Präparation und Anwendungsmöglichkeiten

Radioaktiv markierte Präparate haben in denletzten Jahren in schnell zunehmendem Maße Eingang in die klinische Medizin gefunden. Sie sind beieiner Reihe von Indikationen schon jetzt außerordentlich wertvolle Hilfsmittel bei der Diagnose, besonders bei der Prüfung von Organfunktionen.     

Biomimetic Mineralization of Protein Nanogels for Enzyme Protection

Protein nanogels have found a wide variety of applications, ranging from biocatalysis to drug/protein delivery. However, in practical applications, proteins in nanogels may suffer from enzymic hydrolysis and denaturation. Inspired by the structure and functionalities of the fowl eggshells, biomimetic mineralization of protein nanogels was studied in this research. Protein nanogels with embedded porcine pancreas lipase (PPL) in the cross-linked nanostructures were synthesized through the thiol–disulfide reaction between thiol-functionalized PPL and poly(N-isopropylacrylamide) with pendant pyridyl disulfide groups. The nanogels were further reacted with reduced bovine serum albumin (BSA) and BSA molecules were coated on the nanogels. Mineralization of BSA leads to the synthesis of biomineralized shells on the nanogels. With the growth of CaCO₃ on the shells, the nanogels aggregate into suprastructures. Thermogravimetric analysis, XRD, dynamic light scattering, and TEM were employed to study the mechanism of the biomineralization process and analyze the structures of the mineralized nanogels. The biomineralized shells can effectively protect the PPL molecules from hydrolysis by trypsin; meanwhile, the nanosized channels on the mineralized shells allow the transport of small-molecule substrates across the shells. Bioactivity measurements indicate that PPL in the nanogels maintains more than 80 % bioactivity after biomineralization.     

胎儿脐带血铅水平与钙、锌、铁的关系研究

目的研究胎儿脐带血中的铅与钙、锌、铁的含量以及两两之间的相关性。方法采用原子吸收光谱法对398例脐带血铅和钙、锌、铁的含量进行测定,并对它们进行相关性分析。结果 398例脐带血铅和钙、锌、铁的质量浓度分别为铅(37.96±17.78)μg/L、钙(1.51±0.29)mmol/L、锌(30.01±11.14)μmol/L、铁(8.63±1.39)mmol/L。线性回归分析显示:铅与钙(r=-0.563,P0.01)、铅与锌(r=-0.424,P0.01)有相关性,铅与铁无显著相关(r=0.018,P0.05)。结论随着胎儿体内血铅水平的上升,二价元素钙、锌含量有下降趋势,即中毒元素铅会干扰胎儿体内的必需二价元素的代谢。     

MASS SPECTROMETRIC FRAGMENTATION OF UNSYMMETRICALLY SUBSTITUTED METHYLPHOSPHONATE DIESTERS

Abstract

A series of structurally related unsymmetrically substituted methylphosphonate diesters have been synthesised and subjected to electron impact (El) mass spectral studies. These studies though aimed at total identification of the compounds, resulted in certain interesting observations and hence are being reported. In order to confirm the observations under electron impact and to support the mechanism of fragmentation we have also performed MSNS experiments in both daughter ion and parent ion modes.     

Amorphous Calcium Phosphates: Solvent-Controlled Growth and Stabilization through the Epoxide Route

Calcium phosphates stand among the most promising nanobiomaterials in key biomedical applications, such as bone repairment, signalling or drug/gene delivery. Their intrinsic properties as crystalline structure, composition, particle shape and size define their successful use. Among these compounds, metastable amorphous calcium phosphate (ACP) is currently gaining particular attention due to its inherently high reactivity in solution, which is crucial in bone development mechanisms. However, the preparation of this highly desired (bio)material with control over its shape, size and phase purity remains as a synthetic challenge. In this work, the epoxide route was adapted for the synthesis of pure and stable ACP colloids. By using biocompatible solvents, such as ethylene glycol and/or glycerine, it was possible to avoid the natural tendency of ACP to maturate into more stable and crystalline apatites. Moreover, this procedure offers size control, ranging from small nanoparticles (60 nm) to micrometric spheroids (>500 nm). The eventual fractalization of the internal mesostructured can be tuned, by simply adjusting the composition of the ethylene glycol:glycerine solvent mixture. These findings introduce the use of green solvents as a new tool to control crystallinity and/or particle size in the synthesis of nanomaterials, avoiding the use of capping agents and preserving the natural chemical reactivity of the pristine surface.     

Corrosion inhibition of ammonium molybdate for AA6061 alloy in NaCl solution and its synergistic effect with calcium gluconate

The corrosion inhibition of ammonium heltamolybdate (AH) and calcium gluconate (CG) for AA6061 alloy in 3% NaCl solution was investigated by the electrochemical measurements. It indicates that AH inhibits the corrosion of AA6061 alloy and acts as an anodic inhibitor. Maximum inhibition efficiency reaches 74.3% at the concentration of 1 × 10^?4 mol.l^?1 AH. The results of the electrochemical studies reveal AH is physically adsorbed on the AA6061 alloy surface and the adsorption follows Langmuir isotherm. The combination of AH and CG enhances the inhibition efficiency to 95.9%. The enhanced inhibition is attributed to the promotion of AH adsorption by CG. The mixture of AH and CG is a mixed‐type inhibitor and renders the corrosion potential to more positive values. Copyright © 2011 John Wiley & Sons, Ltd.     

手持技术测定钙尔奇D片中的钙含量

利用二氧化碳传感器测定钙尔奇D片中的钙含量，解决二氧化碳含量不好直接测定的问题，帮助学生提升定量认识，同时体验多种数据记录与处理方式，感受信息技术的魅力。