Preparation and Characterization of a Novel Drug Delivery System: Biodegradable Nanoparticles in Thermosensitive Chitosan/Gelatin Blend Hydrogels

A novel injectable in situ gelling drug delivery system (DDS) consisting of biodegradable N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanoparticles and thermosensitive chitosan/gelatin blend hydrogels was developed for prolonged and sustained controlled drug release. Four different HTCC nanoparticles, prepared based on ionic process of HTCC and oppositely charged molecules such as sodium tripolyphosphate, sodium alginate and carboxymethyl chitosan, were incorporated physically into thermosensitive chitosan/gelatin blend solutions to form the novel DDSs. Resulting DDSs interior morphology was evaluated by scanning electron microscopy. The effect of nanoparticles composition on both the gel process and the gel strength was investigated from which possible hydrogel formation mechanisms were inferred. Finally, bovine serum albumin (BSA), used as a model protein drug, was loaded into four different HTCC nanoparticles to examine and compare the effects of controlled release of these novel DDSs. The results showed that BSA could be sustained and released from these novel DDSs and the release rate was affected by the properties of nanoparticle: the slower BSA release rate was observed from DDS containing nanoparticles with a positive charge than with a negative charge. The described injectable drug delivery systems might have great potential application for local and sustained delivery of protein drugs.     

Bio-friendly synthesis of ZnO nanoparticles in aqueous solution at near-neutral pH and low temperature

ZnO nanoparticles are synthesized using a new bio-friendly method. The experimental conditions are very mild: aqueous solution at near-neutral pH and 37 degrees C. The as-obtained nanoparticles show the stable wurtzite structure without the need of annealing. The two reagents used are aqueous solutions of zinc nitrate and buffer tris(hydroxymethyl)aminomethane. This is a standard nontoxic buffer and inert to a wide variety of chemicals and biomolecules, therefore extremely satisfactory for biochemical reactions. Furthermore, this is a polydentade ligand which adsorbs strongly on one or more surfaces of ZnO inhibiting its crystal growth and yielding nearly spherical ZnO nanoparticles. Our objective is to use the crystallization method described here for further incorporation of biomolecules as additives in the reaction solution, aiming at the formation of ZnO with new physical properties.     

Evolutional kinetics of metal-polymer complexes formation

Under the conditions of polydental binding, metal ions couple azacrown ether links of the polymer, limiting segmental chain mobility and decreasing statistical weight of the states available for complex formation. According to the rate constant dependence on conversion extent two different regimes of the complex formation reaction may be given: 1) retardation resulting from decreasing reactivity, the measured rate constant decreases by a few orders of magnitude in the course of time; 2) retardation followed by increasing reactivity, the observed rate constant remains unchangeable. The process covering conformational nonequilibrium states of macromolecular coil makes it dependent on the system prehistory which violates the law of mass action. The couplings being labile, the instantaneous value of pseudomonomolecular rate constant of the reaction is a function of conversion extent on metal and is not dependent on absolute polymer uptake by metal. The reaction rate in each point does not depend only on reagents concentration ratio but also on the character of metal ion distribution along the polymer chain obtained to the given moment. At complex formation with “hard” couplings the increase of metal concentration makes the effective retardation of the process change, whereas initial parts of the kinetic curves remain practically the same. In this system pseudomonomolecular rate constant does not seem to be a function of conversion extent, but is defined by absolute quantity of the formerly bound metal. Formal application of the law of mass action in this case is useless, it is necessary to apply distribution function on reactivity. Unlike solid phase systems nonequivalent character of reaction sites in the polymer is of evolution character, i.e.it arises in the course of the reaction on the account of polymer coil conformation change.     

Voltammetric monitoring of gold nanoparticle formation facilitated by glycyl-L-tyrosine: relation to electronic spectra and transmission electron microscopy images

Voltammetric techniques have been introduced to monitor the formation of gold nanoparticles produced via the reaction of the amino acid glycyl-L-tyrosine with Au(III) (bromoaurate) in 0.05 M KOH conditions. The alkaline conditions facilitate amino acid binding to Au(III), inhibit the rate of reduction to Au(0), and provide an excellent supporting electrolyte for voltammetric studies. Data obtained revealed that a range of time-dependent gold solution species are involved in gold nanoparticle formation and that the order in which reagents are mixed is critical to the outcome. Concomitantly with voltammetric measurements, the properties of gold nanoparticles formed are probed by examination of electronic spectra in order to understand how the solution environment present during nanoparticle growth affects the final distribution of the nanoparticles. Images obtained by the ex situ transmission electron microscopy (TEM) technique enable the physical properties of the nanoparticles isolated in the solid state to be assessed. Use of this combination of in situ and ex situ techniques provides a versatile framework for elucidating the details of nanoparticle formation.     

The Kinetic Rate Law for the Autocatalytic Growth of Citrate‐Stabilized Silver Nanoparticles

The formation of sodium citrate stabilized spherical silver nanoparticles synthesized by homogeneous nucleation in aqua solutions was monitored by the method of direct potentiometry. It was observed that the kinetic curve of Ag⁺ ions reduction can be described by the Finke–Watzky (FW) autocatalytic two–step mechanism in the case of a large excess of hydrazine and NaOH. To expand the FW minimalistic model, the impact of the starting concentrations of the reagents on the kinetics of Ag nanoparticles synthesis was studied. It was determined that the nucleation stage is limited by the homogeneous process of ions Ag⁺ reduction, and the reaction orders for the all reagents are calculated. A surface–dependent model of Ag nanoparticle growth is proposed, which takes into account the change in the hydrazine and alkali concentrations; the rate constants of the pseudoelementary reactions are also calculated.     

Toxicological Effects of Metal Nanoparticles Employed in Biomedicine: Biocompatibility,Clinical Trials,and Future Perspective

Metal nanoparticles play a crucial role in the medical industry due to its desirable properties such as antimicrobial activity, anti-cancer property, and its application in disease diagnostics. These properties enable the nanoparticles to be used as efficient medical devices for various treatments as well as drug delivery systems. Despite all the positives, metal nanoparticles are known for causing toxicity in the living system. The toxicological effects of metal nanoparticles are due to their size, surface*e coating, and the dose administered. Therefore, it is important to study the toxic effects of these nanoparticles before they are used as medical devices for various treatments. This review focuses on the five major metal nanoparticles used in the medical field, namely; silver, gold, iron oxide, zinc oxide, and titanium dioxide nanoparticles. The non-exhaustive review consists of an introduction to the toxicological effects of these nanoparticles, the biocompatibility, and the current and future clinical perspective on metal nanoparticles.     

Thermoresponsive magnetic colloids

The combination of magnetic nanoparticles with thermoresponsive polymer systems leads to the formation of hybrid particle dispersions or composites with a variety of interesting properties and perspectives, including instant dispensability, thermoreversible formation of magnetic fluids, and novel magnetoresponsive properties. Special interest is gained by the magnetic heatability of magnetic particles that allows the activation of thermal effects by the application of a high-frequency electromagnetic field. This review summarizes the recent developments in this young field of research with application potential for magnetic separation, drug release systems, and for sensor and actuator purposes.     

Recovery of heavy metal ions with calcium peroxide microparticles

Sorption properties of micrometer calcium peroxide particles produced by the chemical reaction between calcium hydroxide and hydrogen peroxide were studied. The dependences of the sorption properties of CaO₂ particles on temperature and acidity of the medium were used to find the optimal values of these parameters at which the sorption of metals is at the maximum. It was shown that CaO₂ particles are nearly as good in sorption properties with hematite and goethite nanoparticles and possess antifungal properties exceeding the corresponding characteristics of sulfur and silver nanoparticles. The simplicity of the method used to obtain the product containing 73% CaO₂, low expenditure due to the application of large-tonnage starting reagents, and its good sorption and antimicrobial properties make it possible to recommend this compound for purification of wastewater, natural water basins, and soil to remove heavy metal ions, with the simultaneous detoxication of these objects.     

Kinetics and mechanism of oxidation of N, N'-dimethylaminoiminomethanesulfinic acid by acidic bromate

The major metabolites of the physiologically active compound dimethylthiourea (DMTU), dimethylaminoiminomethansesulfinic acid (DMAIMSA), and dimethylaminoiminomethanesulfonic acid (DMAIMSOA) were synthesized, and their kinetics and mechanisms of oxidation by acidic bromate and aqueous bromine was determined. The oxidation of DMAIMSA is much more facile and rapid as compared to a comparable oxidation by the same reagents of the parent compound, DMTU. The stoichiometry of the bromate-DMAIMSA reaction was determined to be 2BrO 3 (-) + 3NHCH 3(NCH 3)CSO 2H + 3H 2O --> 3SO 4 (2) (-) + 2Br (-) + 3CO(NHCH 3) 2 + 6H (+), with quantitative formation of sulfate. In excess bromate conditions, the stoichiometry was 4BrO 3 (-) + 5NHCH 3(NCH 3)CSO 2H + 3H 2O --> 5SO 4 (2) (-) + 2Br 2 + 5CO(NHCH 3) 2 + 6H (+). The direct bromine-DMAIMSA reaction gave an expected stoichiometric ratio of 2:1 with no further oxidation of product dimethylurea (DMU) by aqueous bromine. The bromine-DMAIMSA reaction was so fast that it was close to diffusion-controlled. Excess bromate conditions delivered a clock reaction behavior with the formation of bromine after an initial quiescent period. DMAIMSOA, on the other hand, was extremely inert to further oxidation in the acidic conditions used for this study. Rate of consumption of DMAIMSA showed a sigmoidal autocatalytic decay. The postulated mechanism involves an initial autocatalytic build-up of bromide that fuels the formation of the reactive oxidizing species HBrO 2 and HOBr through standard oxybromine reactions. The long and weak C-S bond in DMAIMSA ensures that its oxidation goes directly to DMU and sulfate, bypassing inert DMAIMSOA.     

High-performance thin-layer chromatography method for the quantification of quetiapine fumarate and its related genotoxic impurities using green solvents

A novel high-performance thin-layer chromatographic (HPTLC) analytical method has been developed and optimized for the quantification of quetiapine fumarate (QF) and its two genotoxic impurities in drug substance and drug product. The desired separation was achieved on 60F₂₅₄ pre-coated HPTLC plates using combination of green solvents, ethyl acetate‒ethanol‒n-heptane (5:1:4, V/V) as developing solvents. The detection wavelength used for quantification was 229 nm. QF and its two related genotoxic impurities, namely, 2-chloroaniline and 2-aminodiphenylsulfide, were well resolved from one another with retention factor values of 0.13 ± 0.02, 0.57 ± 0.02 and 0.76 ± 0.02, respectively. The optimized method was validated according to the guidelines laid down by the International Council for Harmonisation. The linearity was determined in the range of 100–600 ng/spot for QF and 10‒60 ng/spot for its two related genotoxic impurities; R² ≥ 0.993. The method exhibited precision along with good accuracy, where 0.51, 0.86 and 1.86. The percentage recoveries obtained for 2-chloroaniline and 2-aminodiphenylsulfide were 99.04‒101.04%. The developed method can be successfully used for the analysis of drug samples.

     

制备高活性纳米零价铁的甘露醇改性机理

纳米零价铁(Nano zero-valent iron,nZVI)被广泛应用于水污染治理,高纯度且分散性良好的nZVI的制备方法一直是研究热点.本文采用含不同羟基数目的醇(乙醇、乙二醇、赤藓糖醇、甘露醇和山梨醇)作为改性剂,分别制备得到n ZVI-EA,nZVI-EG,nZVI-ER,nZVI-M和nZVI-S样品.将上述样品应用于水中微囊藻毒素(Microcystin-LR,MC-LR)的还原去除.结果表明,随着改性剂羟基数目的增多,改性nZVI的抗氧化能力和分散性增强,对MC-LR的降解反应速率也随之提高.nZVI-M去除MC-LR的表面积校正特征速率常数(79.35×10^-5L·m^?2·min^?1)是nZVI-S(8.55×10^-5 L·m^?2·min^?1)的9.3倍,是未改性样品nZVI₀(1.30×10^-5 L·m^?2·min^?1)的61.0倍.通过X射线衍射...     

点击化学在食品安全检测中的应用研究进展

点击化学因具有反应模块化、无有毒有害副产物、反应效率高等出色的反应性能备受关注,是继组合化学之后又一新型合成技术,在材料表面功能化、大分子聚合物的合成、生物标记等领域得到了广泛应用。点击反应试剂的活性基团易于修饰在其他化学基团上,表明点击反应有望作为中间反应介导特定反应的信号转换或放大。近几年出现了大量基于点击化学构建的一系列分析检测方法,此类分析方法具有检测限低、线性范围广、可对目标分析物进行准确定量的优势,有着良好的应用前景。经典的点击反应——“叠氮-炔环加成(CuAAC)”是点击反应中应用最为广泛的反应,具有传感反应所需的几个独特优势：(1)以Cu+作为催化剂可极大提高反应效率以及反应灵敏度;(2)炔烃和叠氮基间的正交反应决定了良好的反应特异性;(3)反应对环境条件(温度、水、pH值等)不敏感,能够在室温和水溶剂条件下进行。这些良好的反应性能使得利用CuAAC反应构建灵敏度高、特异性好且稳定性强的传感检测方法成为可能。食品安全检测是控制食品中危害物、保障公众健康的重要手段。当前食品安全监测常用的技术手段几乎都依赖于一些笨重的仪器设备而无法具有较高检测效率,点击化学的优越性能为食品安全检测提供了新的思路。该文综述了点击化学的概念、主要反应类型、反应原理以及特点,对基于点击化学的一系列快速检测方法如比色法、荧光法、电化学法等进行列表比较,并着重介绍了CuAAC反应在检测食品成分及添加剂、农残兽残、真菌毒素、重金属以及食源性致病菌方面的应用实例,最后指出了现阶段CuAAC反应在应用中存在的不足,并对其在食品安全检测等研究领域的应用前景进行了展望。     

Exploiting the oxidative coupling reaction of MBTH for indapamide determination

The oxidative coupling reaction between aromatic amines and 3-methylbenzothiazolin-2-one hydrazone (MBTH) in the presence of cerium(IV) has been extensively used with quantitative analytical purposes. Nevertheless, a literature survey reveals that different wavelengths (visible range) can be used to monitor the reaction products when using MBTH and Ce(IV) as colour developing reagents.In the present work, the oxidative coupling reaction of indapamide (an oral antihypertensive diuretic drug) with MBTH in the presence of cerium(IV) was evaluated using distinct reaction approaches and was implemented in an automated multipumping flow system. The developed methodology was applied in the spectrophotometric control of the drug in pharmaceutical formulations. The optimization of the proposed multipumping flow system was performed by using an experimental design approach, namely by exploiting a Plackett-Burman factorial design and a central cubic faces design.This work revealed the formation of products with different reaction kinetics, chemical stabilities and absorbance spectra, depending on the sequence of addition of the reagents. By exploiting a specific sequence in the addition of reagents, the proposed automatic system allowed the rapid quantification of indapamide in pharmaceutical formulations, with a determination rate of about 25 h⁻¹, and a relative deviation under 2.1% when comparing with the reference procedure. Detection limit was approximately 1 mg L⁻¹.     

Electrohydrodynamic atomization for biodegradable polymeric particle production

Electrohydrodynamic atomization (EHDA) has many applications such as electrospray ionization in mass spectroscopy, electrospray deposition of thin films, pharmaceutical productions, and polymeric particle fabrications for drug encapsulation. In the present study, EHDA was employed to produce biodegradable polymeric micro- and nanoparticles. The effects of processing parameters such as polymer concentration, flow rate, surfactants, organic salt, and setup configurations on the size and morphology of polymeric particles were investigated systematically. By changing the various processing parameters, controllable particle shape and size can be achieved. PLGA nanoparticles with size of around 250 nm can be obtained by using organic salts to increase the conductivity of the spraying solution even at a relatively high flow rate. A higher flow rate has the advantage of producing a stable cone spray and can be easily reproduced. Solid and porous particles can be fabricated using different experimental setups to control the organic solvent evaporation rate. Also, paclitaxel, a model antineoplastic drug, was encapsulated in polymeric particles which can be employed for controlled release applications. In short, EHDA is a promising technique to fabricate polymeric micro- or nanoparticles which can be used in drug delivery systems.     

A mechanistic and kinetic study of the formation of metal nanoparticles by using synthetic tyrosine-based oligopeptides

Synthetic oligopeptides containing redox-active tyrosine residues have been employed to prepare gold and silver nanoparticles. In this reduction process an electron from the tyrosinate ion of the peptide is transferred to the metal ion at basic pH through the formation of a tyrosyl radical, which is eventually converted to its dityrosine form during the reaction. This reaction mechanism was confirmed from UV-visible, fluorescence, and EPR spectroscopy and was found to be pH-dependent. Transmission electron microscopy measurement shows that the average size and the monodispersity of gold nanoparticles increase as the number of tyrosine residues in the peptide increases. The kinetic study, based on spectrophotometric measurements of the surface plasmon resonance optical property, shows that the rate of formation of gold nanoparticles was much faster at higher pH than at lower pH and was also dependent on the number of tyrosine residues present in the peptide. The dityrosine form of the peptide was found to retain reducing properties like those of tyrosine in basic medium.     

Preparation and characterisation of Na2S and ZnSO4 nanoparticles in water/sodium bis(2-ethylhexyl)sulphosuccinate/n-heptane microemulsions

The preparation procedure for nanoparticles of the water-soluble salts Na₂S and ZnSO₄, two commonly used reagents to synthesise ZnS nanoparticles, by evaporation of volatile components of salt-containing water-in-oil microemulsions is described. In suitable conditions, the evaporation leads to the formation of dry salt–surfactant composites and to the formation of Na₂S or ZnSO₄ nanoparticles. It was found that the salt–surfactant composites can be totally redissolved in a dry apolar organic solvent allowing the formation of virtually water-free solutions containing a considerable amount of the water-soluble salts. The presence of nanoparticles in these solutions and in the composites has been proved by small-angle X-ray scattering and transmission electron microscopy, respectively. By mixing these solutions, the solid–solid reaction between Na₂S and ZnSO₄ nanoparticles leading to the formation of very small-sized ZnS nanoparticles has been ascertained by UV spectrophotometry. Received: 09 February 2001 Accepted: 19 March 2001     

Grignard functionalization of Weinreb amide-modified Au nanoparticles

Reactions of Grignard and organolithium reagents are staple transformations in organic chemistry. However, their use in the chemical functionalization of monolayer-protected metallic nanoparticles is unprecedented. In this letter, we report the reaction of Au nanoparticles bearing a mixed monolayer of alkanethiol ligands that are methyl- and N-methoxy- N-methyl amide-terminated. The latter of these rapidly undergoes reaction with organometallic reagents, achieving high yields (in some cases, nearly quantitative) in only a few hours without the need for high pressure, temperature or catalysts. We assess the feasibility of this reaction with a range of organometallic reagents on the basis of both surface reaction yield and also the stability of the particles (defined as the mass % Au particles recovered vs a control). Demonstrating the utility of these strong organometallic reagents opens the door to a large class of reactions that are underutilized within the field of nanomaterials.     

叶酸靶向乙酰普鲁兰纳米粒的制备及其靶向作用

以普鲁兰多糖为主链, 通过乙酰化反应合成了疏水性的乙酰普鲁兰(PA), 然后以N,N′-二环己基碳二亚胺(DCC)为偶联剂, 4-二甲氨基吡啶(DMAP)为催化剂, 将叶酸与PA偶联(FPA); 采用¹H NMR和X射线晶体衍射(XRD)等方法对产物结构进行了表征. 采用溶剂扩散法制备包载表阿霉素的PA和FPA纳米粒, 载药纳米粒形态为球形, 动态光散射粒径分析显示载药纳米粒粒径随载药量增加而增大. 透析法测定纳米粒中表阿霉素的体外释放表明, FPA纳米粒中药物释放速度快于PA纳米粒; 采用激光共聚焦显微镜观察PA/EPI及FPA/EPI纳米粒在KB细胞的摄取情况, 结果表明, FPA/EPI纳米粒进入细胞主要通过叶酸受体途径, 而PA/EPI纳米粒进入细胞与叶酸受体无关, 提示FPA将成为具有一定肿瘤靶向作用的新型载体.     

环糊精衍生物在金属催化有机合成中的应用

综述了环糊精(包括α-环糊精,β-环糊精和γ-环糊精)衍生物在金属催化有机合成中的应用,主要包括其作为金属离子配体、金属纳米粒子稳定剂和反相相转移催化剂在氧化、水解、还原、偶联等金属催化反应中的应用.其中环糊精衍生物作为金属离子配体应用最广,由于环糊精部分与底物形成包结络合物,拉近了底物和具有催化活性的金属离子的距离,并固定了底物的反应部位,往往可以显著提高催化反应的反应速率,增强反应的区域选择性和对映选择性.