Optimization of taste-masking on ibuprofen microspheres with selected structure features

The microsphere was a primary particulate system for taste-masking with unique structural features defined by production process. In this article, ibuprofen lipid microspheres of octadecanol and glycerin monostearate were prepared to mask the undesirable taste of ibuprofen via three kinds of spray congealing processes, namely, air-cooling, water-cooling and citric acid solution-cooling. The stereoscopic and internal structures of ibuprofen microspheres were quantitatively analyzed by synchrotron radiation X-ray micro-computed tomography(SR-μCT) to establish the relationship between the preparation process and microsphere architectures. It was found that the microstructure and morphology of the microspheres were significantly influenced by preparation processes as the primary factors to determine the release profiles and taste-masking effects. The sphericity of ibuprofen microspheres congealed in citric acid solution was higher than that of other two and its morphology was more regular than that being congealed in air or distilled water, and the contact angles between congealing media and melted ibuprofen in octadecanol and glycerin monostearate well demonstrated the structure differences among microspheres of three processes which controlled the release characteristics of the microspheres. The structure parameters like porosity, sphericity, and radius ratio from quantitative analysis were correlated well with drug release behaviors. The results demonstrated that the exterior morphology and internal structure of microspheres had considerable influences on the drug release behaviors as well as taste-masking effects.

First Rocketsonde Launched from an Unmanned Semi-submersible Vehicle

The unmanned semi-submersible vehicle(USSV) developed by the unmanned surface vehicle team of the Institute of Atmospheric Physics is an unmanned, rugged, and high-endurance autonomous navigation vessel designed for the collection of long-term, continuous and real-time marine meteorological measurements, including atmospheric sounding in the lower troposphere. A series of river and sea trials were conducted from May 2016 to November 2017, and the first rocketsonde was launched from the USSV. Real-time meteorological parameters in the marine atmospheric boundary layer(MABL) were obtained, including sea surface temperature, and vertical profiles of the pressure, temperature, relative humidity, wind speed,and wind direction. These data are extremely useful and important for research on air–sea interactions, sea surface heat and latent heat flux estimations, MABL modeling, and marine satellite product validation.

Discussing the Dietary Regimen and Disease Prevention and its Application as an Anti‑epidemic Measure

This article discusses the role of dietary regimen in the traditional culture of Chinese medicine according to its origin.Dietary regimen is a technique that inherits the traditional culture of Chinese medicine.Through analysis of the characteristics of the dietary regimen and the discussion of the idea of disease prevention,the application of the dietary regimen in disease prevention is sought.Under the guidance of three key factors,the application of the dietary regimen in disease prevention is mainly manifested in two aspects.First,the dietary regimen can be used to guide the daily reasonable diet to maintain the human body in a balance of Yin and Yang,which could prevent the occurrence of diseases.Second,on the basis of minimizing health loss,it can be used for disease treatment,adjuvant treatment,and rehabilitation.Finally,taking preventive treatment as the guiding ideology,the application of a dietary regimen as an“anti‑epidemic”was briefly discussed.

Discussing the Dietary Regimen and Disease Prevention and its Application as an Anti-epidemic Measure

This article discusses the role of dietary regimen in the traditional culture of Chinese medicine according to its origin.Dietary regimen is a technique that inherits die traditional culture of Chinese medicine.Through analysis of the characteristics of the dietary regimen and the discussion of the idea of disease prevention,the application of the dietary regimen in disease prevention is sought.Under the guidance of three key factors,the application of the dietary regimen in disease prevention is mainly manifested in two aspects,h irst,the dietary regimen can be used to guide the daily reasonable diet to maintain the human body in a balance of Yin and Yang,which could prevent the occurrence of diseases.Second,on the basis of minimizing health loss,it can be used for disease treatment,adjuvant treatment,and rehabilitation.Finally,taking preventive treatment as the guiding ideology,the application of a dietary regimen as an"anti-epidemic"was briefly discussed.

具有TFCP2基因重排横纹肌肉瘤临床病理学特征

目的探讨具有TFCP2基因重排横纹肌肉瘤(rhabdomyosarcomas, RMS)的临床病理学特征。方法收集2例具有TFCP2基因重排RMS的临床病理及分子遗传学检测资料, 同时复习相关文献。结果例1女, 31岁, 肿物位于左上牙龈;例2女, 49岁, 肿物位于右上颌后牙区。镜下形态:例1由条束状、旋涡状的短/胖梭形细胞构成;例2肿瘤与骨组织混杂生长, 长梭形细胞为主伴有少量上皮样细胞。免疫表型, 例1肿瘤细胞部分表达结蛋白及广谱细胞角蛋白, 例2肿瘤细胞弥漫表达结蛋白;2例均MyoD1弥漫阳性, Myogenin阴性, 间变性淋巴瘤激酶Ventana-D5F3部分阳性。间期荧光原位杂交(FISH)检测到TFCP2基因易位。二代测序检测到EWSR1-TFCP2融合基因。例1术后5个月左颈淋巴结转移, 例2术后32个月前腭部肿瘤复发。结论具有TFCP2基因重排RMS是RMS的一组特殊亚群, 好发于骨, 特别是青年患者颅面骨, 表现为上皮样细胞和/或梭形细胞形态, 预后不良。

The contribution of absorption of integral nanocrystals to enhancement of oral bioavailability of quercetin

In this study,self-discriminating hybrid nanocrystals was utilized to explore the biological fate of quercetin hybrid nanocrystals(QT-HNCs)with diameter around 280 nm(QT-HNCs-280)and550 nm(QT-HNCs-550)following oral and intravenous administration and the contribution of integral nanocrystals to oral bioavailability enhancement of QT was estimated by comparing the absolute exposure of integral QT-HNCs and total QT in the liver.Results showed that QT-HNCs could reside in vivo as intact nanocrystals for as long as 48 h following oral and intravenous administration.A higher accumulation of integral QT-HNCs in liver and lung was observed for both oral and intravenous administration of QT-HNCs.The particle size affects the absorption and biodistribution of integral QT-HNCs and total QT.As compared to QT-HNCs-550,QT-HNCs-280 with smaller particle size is more easily absorbed,but dissolves faster in vivo,leading to higher distribution of QT(146.90 vs.117.91 h·mg/mL)but lower accumulation of integral nanocrystals(6.82 e10 vs.15.27 e10 h·[p/s]/[μW/cm2])in liver following oral administration.Due to its slower dissolution and enhanced recognition by RES,QT-HNCs-550 with larger diameter shows higher liver distribution for both of QT(1015.80 h·mg/mL)and integral nanocrystals(259.63 e10 h·[p/s]/[μW/cm2])than those of QT-HNCs-280(673.82&77.66 e10 h·[p/s]/[μW/cm2])following intravenous administration.The absolute exposure of integral QT-HNCs in liver following oral administration of QT-HNCs are 8.78%for QT-HNCs-280 and 5.88%for QT-HNCs-550,while the absolute exposure of total QT for QT-HNCs-280 and QT-HNCs-550 are 21.80%and 11.61%,respectively.Owing to imprecise quantifcation method,a surprisingly high contribution of integral QT-HNCs to oral bioavailability enhancement of QT(40.27%for QT-HNCs-280 and 50.65%for QT-HNCs-550)was obtained.These results revealed signifcant difference in absorption and biodistrbution between integral nanocrystals and overall drugs following oral and intravenous administration of QT-HNCs,and provided a meaningful reference for the contribution of integral nanocrystals to overall bioavailability enhancement.

Drug nanoclusters formed in confined nano-cages of CD-MOF: dramatic enhancement of solubility and bioavailability of azilsartan

Tremendous efforts have been devoted to the enhancement of drug solubility using nanotechnologies, but few of them are capable to produce drug particles with sizes less than a few nanometers. This challenge has been addressed here by using biocompatible versatile γ-cyclodextrin(γ-CD) metal-organic framework(CD-MOF) large molecular cages in which azilsartan(AZL) was successfully confined producing clusters in the nanometer range. This strategy allowed to improve the bioavailability of AZL in Sprague–Dawley rats by 9.7-fold after loading into CD-MOF. The apparent solubility of AZL/CD-MOF was enhanced by 340-fold when compared to the pure drug. Based on molecular modeling, a dual molecular mechanism of nanoclusterization and complexation of AZL inside the CD-MOF cages was proposed, which was confirmed by small angle X-ray scattering(SAXS) and synchrotron radiation-Fourier transform infrared spectroscopy(SR-FTIR) techniques. In a typical cage-like unit of CD-MOF, three molecules of AZL were included by the γ-CD pairs, whilst other three AZL molecules formed a nanocluster inside the 1.7 nm sized cavity surrounded by six γ-CDs. This research demonstrates a dual molecular mechanism of complexation and nanoclusterization in CD-MOF leading to significant improvement in the bioavailability of insoluble drugs.

Mechanistic studies of the transport of peimine in the Caco-2 cell model

Fritillaria thunbergii Miq. has been widely used in traditional Chinese medicine for its expectorant, antitussive, antiinflammatory and analgesic properties. Moreover, modern pharmacological studies have demonstrated that F. thunbergii Miq. has efficacy in the treatment of leukemia and cancers of the liver and cervix. Although the alkaloid, peimine, is largely responsible for these pharmacological effects, it has very low oral bioavailability. The aim of this study was to investigate the intestinal absorption of peimine in Caco-2 cell monolayers. Having demonstrated that peimine is non-toxic to Caco-2 cells at concentrations o200 μmol/L, the effect of peimine concentration, p H, temperature, efflux transport protein inhibitors and EDTA-Na_2 on peimine transport were studied. The results show that peimine transport is concentration-dependent; that at p H 6.0 and 7.4, the P_(app(AP-BL))of peimine is not significantly different but the Papp(BL-AP)) is; that both Papp(AP-BL)and P_(app(BL-AP))at 4 1C are significantly higher than their corresponding values at 37 1C; that the P-glycoprotein(P-gp) inhibitors, verapamil and cyclosporin A, increase absorption of peimine; and that EDTA-Na2 has no discernible effect. In summary,the results demonstrate that the intestinal absorption of peimine across Caco-2 cell monolayers involves active transport and that peimine is a substrate of P-gp.

Triptolide-loaded microemulsion-based hydrogels: physical properties and percutaneous permeability

Triptolide is a diterpenoid compound that inhibits the inflammation of rheumatoid arthritis(RA).However,the use of triptolide is limited due to its strong gastrointestinal toxicity.The purpose of this work was to develop a transdermal delivery system for triptolide to reduce this toxicity.A microemulsion-based hydrogel(MBH)was prepared from the combination of Gemseal 40-oleic acid as oil phase,Tween 80-labrasol as surfactant,anhydrous ethanol as co-surfactant,water as aqueous phase and Poloxamer 407 as hydrogel matrix.Rheological measurements,environmental scanning electron microscopy(ESEM)and transdermal experiments in vitro were used to characterize triptolide-loaded and blank MBH preparations.The effects of Poloxamer 407 and triptolide on the rheological properties and microstructures of the MBH were determined.Transparent and homogeneous MBH could only be formed when the concentration of Poloxamer 407 in the selected O/W microemulsion was in the range of 14.0–16.0%(w/w).When the concentration of Poloxamer 407 increased,the rheological properties such as the yield stresses(sy),storage and loss moduli(G′,G″)of the formulations increased,and the network structures became more compact.The addition of triptolide did not change the interconnected network structures of the MBH preparations.MBH preparations afford a better sustained release profile when compared to microemulsions,a finding confirmed by an in vitro permeation test in mice.MBH appears to be a promising vehicle for transdermal delivery of triptolide.