Tissue distribution and targeting evaluation of TMP after oral administration of TMP-loaded microemulsion to mice

The aim of this study was to quantify the oral delivery systems of Tetramethylpyrazine Microemulsion (TMP ME) to heart, liver, spleen, lung, kidney and brain by comparing TMP level after oral administration at a dose of 100?mg kg^?1 with those of TMP tablet suspension (TMP SWW). This study was taken in mice to develop a suitable analytical methodology in pharmacokinetics studies and to manipulate the tissue distribution and targeting evaluation. Drug concentrations in tissues were determined at different times post-mortem. An HPLC method for separation and quantification of TMP was developed and validated by studying mice tissues. Following oral administration, TMP concentrations in different tissues were constantly detected for quite a long time and finally differed significantly from each other. The AUC rank order 3 of ME group is AUC_liver?> AUC_brain?> AUC_lung?> AUC_spleen?> AUC_heart?> AUC_kidney, while the SWW group is AUC_liver?> AUC_lung?> AUC_spleen?> AUC_heart?> AUC_brain?> AUC_spleen. Especially, the AUC value in brain region (AUC_brain) of ME is 6.06-fold of SWW. The drug relative overall targeting efficiency (RTE) are calculated: heart (7.49%), liver (3.54%), spleen (12.60%), lung (6.02%), kidney (2.86%) and brain (12.51%). The results from ME directly showed obvious targeting transport to the brain. These results indicated that this new family of pharmaceutical carriers can be used for the solubilization and targeted delivery of poorly soluble drugs to various pathological sites in the body.     

Brain targeting of chitosan-based diazepam mucoadhesive microemulsions via nasal route: formulation optimization,characterization, pharmacokinetic and pharmacodynamic evaluation

Objective: The aim of present investigation was to develop microemulsions (MEs) and mucoadhesive microemulsions (MME) of diazepam for brain uptake through nasal administration for the treatment of seizure emergency.

Significance: Status epilepticus (SE) is a medical emergency, requires intravenous administration of diazepam which requires hospitalization of patient. Initiation of therapy at home via nasal administration of diazepam could prevent the damage of brain due to delay of therapy initiation.

Methods: Diazepam MEs were prepared by phase titration method, optimized by using Box–Behnken design. The influence of independent variables oleic acid, surfactant mixture (tween 80:propylene glycol), and water on dependent variables size, flux, and zeta potential was investigated. Optimized MEs, MMEs, and Calmpose (i.v route) were evaluated for pharmacokinetic and pharmacodynamic studies on rats.

Results: MME2 composed of oleic acid (5), surfactant mixture (50), water (45), and chitosan (0.5) showed size of 96.45?nm, PDI 0.21 and zeta potential 13.52?mV. MME2 showed significantly high flux of 846.96?±?34?µg/cm2/h and AUCbrain 1206.49?±?145.8. The drug targeting efficiency (314%) and direct nose-to-brain transport (68.1%) of MME2 were significantly high compared to Calmpose (i.v) and ME. The latency periods of minimal clonal seizures and generalized tonic–clonic seizures of MME2 was significantly increased (p?<?0.0001) compared to drug solution and Calmpose (i.v).

Conclusion: The brain uptake of diazepam from chitosan-based MMEs via nasal route is significantly high compared to i.v route.     

Design,characterization, and evaluation of intranasal delivery of ropinirole-loaded mucoadhesive nanoparticles for brain targeting

Context: Parkinson disease (PD) is a common, progressive neurodegenerative disorder, characterized by marked depletion of striatal dopamine and degeneration of dopaminergic neurons in the substantia nigra.

Objective: The purpose of the present study was to investigate the possibility of targeting an anti-Parkinson’s drug ropinirole (RH) to the brain using polymeric nanoparticles.

Materials and methods: Ropinirole hydrochloride (RH)-loaded chitosan nanoparticles (CSNPs) were prepared by an ionic gelation method. The RH-CSNPs were characterized for particle size, polydispersity index (PDI), zeta potential, loading capacity, entrapment efficiency in vitro release study, and in vivo distribution after intranasal administration.

Results and discussion: The RH-CSNPs showed sustained release profiles for up to 18?h. The RH concentrations (% Radioactivity/g) in the brain following intranasal administration (i.n.) of RH-CSNPs were found to be significantly higher at all the time points compared with RH solution. The concentration of RH was highest in the liver (7.210?±?0.52), followed by kidneys (6.862?±?0.62), intestine (4.862?±?0.45), and lungs (4.640?±?0.92) in rats following i.n. administration of RH-CSNPs. Gamma scintigraphy imaging in rats was performed to ascertain the localization of drug in the brain following intranasal administration of formulations. The brain/blood ratios obtained (0.251?±?0.09 and 0.386?±?0.57 of RH (i.n.) and RH-CSNPs (i.n.), respectively) at 0.5?h are indicative of direct nose to brain transport, bypassing the blood–brain barrier (BBB).

Conclusion: The novel formulation showed the superiority of nose to brain delivery of RH using mucoadhesive nanoparticles compared with other delivery routes reported earlier.     

Synthesis and characterization of ordered mesoporous silica by using polystyrene microemulsion as templates

A simple room temperature synthesis of pure mesoporous silica by using a homemade and functional template: polystyrene microemulsion is reported. The process consists of HCl-catalysed sol-gel reactions of tetraethyl orthosilicate (TEOS) in polystyrene microemulsion, followed by removal of the template via solvent extraction or calcining. X-ray diffraction, Transmission Electron Microscope and N₂ adsorption-desorption isotherms are then used to characterize the mesostructure. The results indicate that the synthesized mesoporous silica has a large BET surface area with more than 900 m²/g, large pore volume with more than 0.8 cm³/g and ordered mesopore-structure. This provides a possible way to control the meso-structure and pore size of mesoporous materials via potential functional templates.     

Tolerogenic Iron Oxide Nanoparticles in Type 1 Diabetes: Biodistribution and Pharmacokinetics Studies in Nonobese Diabetic Mice

Nanoparticle (NP) administration is among the most attractive approaches to exploit the synergy of different copackaged molecules for the same target. In this work, iron oxide NPs are surface‐engineered for the copackaging of the autoantigen proinsulin, a major target of adaptive immunity in type 1 diabetes (T1D), and 2‐(1′H‐indole‐3′‐carbonyl)‐thiazole‐4‐carboxylic acid methylester (ITE), a small drug conditioning a tolerogenic environment. Magnetic resonance imaging (MRI) combined with magnetic quantification are used to investigate NP biokinetics in nonobese diabetic (NOD) mice and control mice in different organs. Different NP biodistribution, with in particular enhanced kidney elimination and a stronger accumulation in the pancreas for prediabetic NOD mice, is observed. This is related to preferential NP accumulation in the pancreatic inflammatory zone and to enhancement of renal elimination by diabetic nephropathy. For both mouse strains, an MRI T2 contrast enhancement at 72 h in the liver, pancreas, and kidneys, and indicating recirculating NPs, is also found. This unexpected result is confirmed by magnetic quantification at different time points as well as by histological evaluation. Besides, such NPs are potential MRI contrast agents for early diagnosis of T1D.     

铁炭复合磁靶向缓释药物载体材料的制备--制备条件对铁炭复合材料磁性能的影响

研究了一种新型铁炭复合磁靶向缓释药物栽体材料的制备方法。用医用活性炭和纳米四氧化三铁粉末球磨制成铁炭复合材料,该材料表面包硅处理后用氢气高温还原,得到可以作为磁靶向缓释药物栽体的铁炭复合材料。考察了制备过程中的包硅和还原工艺条件对铁炭复合材料磁性能的影响。     

改性硅微乳的生产技术及在纺织印染中的应用

通过乳液聚合和本体聚合制备改性硅微乳 ,阐述其工艺流程和操作步骤 ,并讨论了影响乳液聚合和本体聚合的各种因素及适宜的合成条件。提出染整应用中遇到的一些问题     

In vitro and in vivo evaluation of cubosomal in situ nasal gel containing resveratrol for brain targeting

The aim of this study was to enhance the delivery of resveratrol to the brain through the transnasal route by cubosomes. Cubosomes were prepared using glycerol monooleate and Lutrol F127 by probe sonication method. A 3² full factorial design was used for optimization of cubosomes and batch containing 4% w/v glycerol monooleate and 1.5% w/v of Lutrol F 127 was optimized. The selected cubosomal batch was cubical in shape, having mean particle size 161.5?±?0.12?nm. Entrapment efficiency was found to be 83.08% with zeta potential of –20.9?mV. In vitro release of cubosomal batch showed controlled release of drug profile (67%) up to 24?h. The optimized cubosomal dispersion was dispersed into gelling polymer (poloxamer 407) to form in situ gel for nasal use. The optimal cubosomal gel (containing 12% w/v poloxamer 407) had been subjected to ex-vivo permeation and in vivo biodistribution studies. It showed significantly higher transnasal permeation and better distribution to brain, when compared to the drug solution (i.n.) and drug solution (oral). Finally the cubosomal gel could be considered as a promising carrier for brain targeting of Resveratrol (Res) through transnasal route.     

Uptake pathways and subsequent nucleus targeting of tat-conjugated gelatin-siloxane nanoparticles as nonviral gene vector

Novel hybrid biomaterial of Tat peptide modified gelatin-siloxane nanoparticles (Tat-GS NPs), with positive surface potential was synthesised through a two-step sol-gel process. The particles were subsequently tested in vitro with HeLa cells by fluorescent activitated cell sorter analysis, confocal laser scanning microscopy, and transmission electron microscopy to determine whether the functionalisation with Tat peptide allowed particles to transfer across the cell membrane and locate in the nucleus. Our current results indicated that the internalisation of Tat-GS NPs in HeLa cells is time- and concentration- dependent. Moreover, Tat-GS NPs could penetrate the nucleus membrane and enter into nucleus. The Tat-GS/pDNA nanocomplexes were formulated with higher encapsulation efficiency, and exhibited efficient transfection in vitro. Tat-GS NPs are thus considered as novel non-viral vectors will be widely used in further study.     

西洋参中人参皂苷Rg1、Re、Rb1基体标准物质的研制

建立高效液相色谱法和高效毛细管电泳法,对研制的西洋参基体标准物质中人参皂苷Rg₁、Re、Rb₁含量进行准确定值,同时考察了样品的均匀性、稳定性和样品的最小取样量,最后对标准物质的不确定度进行了评定。评定结果为人参皂苷Rg₁、Re、Rb₁含量分别为（1.72±0.14）mg/g、（15.3±1.5）mg/g、（25.8±2.8）mg/g,相对扩展不确定度分别为8.4％、10％、11％,可为西洋参的质量控制提供依据。     

一种高效节能的近共沸制冷剂KLB—1制冷剂替代R22在小型冷库中的应用

用节能型ＫＬＢ－ １ 制冷剂替代Ｒ２２, 作为小型冷库的制冷工质, 并与Ｒ２２ 为工质的相似冷库作比较,在设备未更动和未调换润滑油的情况下,测定了吸排气压力,吸排气温度和能耗情况。结果表明：ＫＬＢ－ １ 具有节省能耗的效果,可以代替Ｒ２２ 直接使用。     

Modelling the initial phase of an epidemic using incidence and infection network data: 2009 H1N1 pandemic in Israel as a case study

This paper presents new computational and modelling tools for studying the dynamics of an epidemic in its initial stages that use both available incidence time series and data describing the population''s infection network structure. The work is motivated by data collected at the beginning of the H1N1 pandemic outbreak in Israel in the summer of 2009. We formulated a new discrete-time stochastic epidemic SIR (susceptible-infected-recovered) model that explicitly takes into account the disease''s specific generation-time distribution and the intrinsic demographic stochasticity inherent to the infection process. Moreover, in contrast with many other modelling approaches, the model allows direct analytical derivation of estimates for the effective reproductive number (R_e) and of their credible intervals, by maximum likelihood and Bayesian methods. The basic model can be extended to include age–class structure, and a maximum likelihood methodology allows us to estimate the model''s next-generation matrix by combining two types of data: (i) the incidence series of each age group, and (ii) infection network data that provide partial information of ‘who-infected-who’. Unlike other approaches for estimating the next-generation matrix, the method developed here does not require making a priori assumptions about the structure of the next-generation matrix. We show, using a simulation study, that even a relatively small amount of information about the infection network greatly improves the accuracy of estimation of the next-generation matrix. The method is applied in practice to estimate the next-generation matrix from the Israeli H1N1 pandemic data. The tools developed here should be of practical importance for future investigations of epidemics during their initial stages. However, they require the availability of data which represent a random sample of the real epidemic process. We discuss the conditions under which reporting rates may or may not influence our estimated quantities and the effects of bias.     

十八胺作为还原剂和包裹剂制备具有SERS活性的金纳米线

采用化学还原方法,在有机相中利用十八胺作为还原剂和包裹剂,在油酸的辅助下,合成了具有一维结构的金纳米线,并将制得的金纳米线用作基底,在其表面获得了罗丹明B分子的SERS光谱,实验结果表明,金纳米线具有良好的SERS活性,有望应用于高灵敏度光学检测。     

Enhancing the Photocatalytic Performance of BiOClxI1−x by Introducing Surface Disorders and Bi Nanoparticles as Cocatalyst

Photocatalysis has emerged as a promising method for industrial sewage elimination. The main bottleneck of this process is the development of an efficient, stable, and cost‐effective catalyst that can oxidize pollution under visible light. Herein, surface disorders and Bi nanoparticles are successfully introduced into BiOCl_xI_1−x nanosheets using low‐cost NaBH₄ as a reductant in a liquid‐phase environment. Benefiting from the enhanced charge separation, transfer, and donor density resulting from the formation of surface disorders, and Bi deposition as cocatalyst, the photocatalytic performance of the reductive BiOCl_xI_1−x nanosheets is fivefold higher than that of the untreated BiOCl_xI_1−x nanosheets for phenol degradation under visible light irradiation. Additionally, the reductive BiOCl_xI_1−x nanosheets have a superior stability after five cycles.     

The Biofunctions of Phytochemicals and Their Applications in Farm Animals: The Nrf2/Keap1 System as a Target

Reactive oxygen species (ROS) can be caused by mechanical, thermal, infectious, and chemical stimuli, and their negative effects on the health of humans and other animals are of considerable concern. The nuclear factor (erythroid-derived 2)-like 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) system plays a major role in maintaining the balance between the production and elimination of ROS via the regulation of a series of detoxifying and antioxidant enzyme gene expressions by means of the antioxidant response element (ARE). Dietary phytochemicals, which are generally found in vegetables, fruits, grains, and herbs, have been reported to have health benefits and to improve the growth performance and meat quality of farm animals through the regulation of Nrf2-mediated phase II enzymes in a variety of ways. However, the enormous quantity of somewhat chaotic data that is available on the effects of phytochemicals needs to be properly classified according to the functions or mechanisms of phytochemicals. In this review, we first introduce the antioxidant properties of phytochemicals and their relation to the Nrf2/Keap1 system. We then summarize the effects of phytochemicals on the growth performance, meat quality, and intestinal microbiota of farm animals via targeting the Nrf2/Keap1 system. These exhaustive data contribute to better illuminate the underlying biofunctional properties of phytochemicals in farm animals.     

基于TiH2原料的粉末冶金Ti-6Al-3Nb-2Zr-1Mo合金的组织与性能研究

目的 研究烧结工艺对Ti-6Al-3Nb-2Zr-1Mo合金组织演变及力学性能的影响.方法 以TiH2粉末为原料,采用粉末冶金工艺制备低成本高性能的Ti-6Al-3Nb-2Zr-1Mo合金,分析合金在不同烧结条件下组织与性能的变化规律.结果 TiH2的脱氢温度区间集中在450～700℃;Ti-6Al-3Nb-2Zr-1...     

锂离子电池正极材料Li1+xV3O8的合成及性能研究

研究了一种新型制备锂离子电池正极材料Li_(1+x)V_3O_8的工艺方法.以NH_4VO_3为原料,通过淬火法制备出V_2O_5溶胶,加入LiOH溶液后,通过喷雾干燥法制备球形前驱体,再通过一定的热处理即制得锂离子电池正极材料Li_(1+x)V_3O_8.试验中,进行了前驱体的DTA/TGA分析;对产物进行了XRD、SEM及电化学性能测试研究.结果表明,经过350℃热处理24h后得到的样品颗粒细小、呈球形、粒径分布均匀、结晶度好,并且还表现出很好的电化学性能,其首次放电比容量高达378mAh·g~(-1),经过10次充放电循环后,其放电比容量为312mAh·g~(-1).