Table of Content

    28 July 2015, Volume 24 Issue 7
    Original articles
    Preparation and anti-MDR tumors study of folate and TPGS dual-modified DSPE-PEG micelles loaded with docetaxel
    Aiting Wang, Shuwen Tong, Xin Hu, Xianrong Qi
    2015, 24(7):  419-426.  DOI: 10.5246/jcps.2015.07.054
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    Multidrug resistance (MDR) operated by P-glycoprotein (P-gp) is one of the major causes in the treatment failure of cancers. In this work,docetaxel-loaded mixed micelles comprised of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene-glycol)2000 (DSPE-PEG2000),D-α-Tocopherylpolyethylene glycol 1000 succinate (TPGS1000) and DSPE-PEG2000-folate were developed to overcome MDR and reduce the side effect of docetaxel in cancer therapy. The diameters of micelles ranged from 13 to 26 nm and the encapsulation efficiencies were all above 85%. The influences of DSPE-PEG2000 and TPGS1000 ratios on the micellar characteristics and anti-resistant tumors effects were evaluated. Micelles with high TPGS1000 amount showed an increased cellular uptake and stronger cytotoxicity against MDR KBv cells. Moreover, the micelles modified by targeting ligand of folic acid exhibited better antitumor effect on folate receptor over-expressing KBv cells.The study provides a method for overcoming MDR in cancer therapy.

    Pharmacokinetics of two components in felodipine-enalapril sustained-release tablets in Chinese healthy volunteers
    Yisha Lv, Liling Ran, Wei Wu, Sanwang Li, Rui Zhou, Fang Tang, Peng Yu, Lingli Mu, Zeneng Cheng
    2015, 24(7):  427-432.  DOI: 10.5246/jcps.2015.07.055
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    To compare the pharmacokinetics properties of enalapril-felodipine sustained-release tablet with enalapril and felodipine in the two reference formulations in Chinese healthy volunteers,the study was designed to a randomized, open label, crossover and two treatment pharmacokinetic study using enalapril-felodipine sustatined-release tablet as the test formulation. A total of 12 individuals were randomly assigned to 2 gorups (6 individuals in each group). The wash-out period was 14 d. Compared with the reference formulations, felodipine in the sustained-release tablet showed significantly sustained-release characteristics, while the pharmacokinetics processes of enalapril and its active metabolite enalaprilat were basically similar in Chinese healthy volunteers.

    Formulation development and evaluation of pioglitazone hydrochloride self-emulsifying drug delivery systems
    Gannu Praveen Kumar, D. Bikshapathi, P. Madhukar
    2015, 24(7):  433-441.  DOI: 10.5246/jcps.2015.07.056
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    As a widely prescribed anti diabetic drug, pioglitazone belongs to class IΙ under BCS and exhibits low and variable oral bioavailability due to its poor aqueous solubility. Its oral absorption is dissolution rate limited, and its solubility and dissolutionrate need to be enhanced in order to increase its oral bioavailability. In the present study, we aimed to screen various oils, surfactantsand cosolvents. The highest solubility was observed in Labrafac, Tween-80 and propylene glycol. Then the feasibility of formulatingpioglitazone SEDDS was evaluated, and the effect of dilution on the dissolution rate and dissolution efficiency of pioglitazone was also analyzed. A comparative evaluation of pioglitazone from SEDDS was made in SGF and 1% SLS. Dissolution of pioglitazone from SEDDS was rapid and higher compared with pure drug. The rate and extent of release of pioglitazone hydrochloride from stable SEDDS (F1) were higher in 1% SLS compared with SGF. The FTIR spectra proved that there was on chemical interaction between excipients and drug. SEM studies confirmed that the size was small and spherical.

    Bioconversion of genistein to (-)-5-hydroxy-equol by a newly isolated cock intestinal anaerobic bacterium
    Yanjing Xie, Ziguang Liu, Yaning Gao, Xiuling Wang, Qinghong Hao, Xiumei Yu
    2015, 24(7):  442-448.  DOI: 10.5246/jcps.2015.07.057
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    A newly isolated bacterium, named as AUH-JLC257, was found to be capable of bioconverting isoflavone genistein to 5-hydroxy-equol under anaerobic conditions. The metabolite 5-hydroxy-equol was identified by using UV spectrum, electrospray ionization mass spectrometry (ESI-MS) as well as 1H and 13C NMR analyses. Chiral stationary-phase high-performance liquid chromatography analysis and specific rotation examination demonstrated that the bio-synthesized 5-hydroxy-equol was just ()-5-hydroxy-equol. The average bioconverting rate was 83.1%, and the strain AUH-JLC257could efficiently transform genisteinat a maximal substrate concentration of 0.6 mmol/L. We, for the first time, showed that the bio-synthesized 5-hydroxy-equol had 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity at concentrations as low as 3.3 µmol/L.In addition, the 16S rRNA gene sequence (1401 bp) of the bacterium strain AUH-JLC257 showed the highest similarity (99.27%) to that ofSlackia equolifaciens strain DZE.

    Simultaneous determination of five major components of Glycyrrhizae Radix et Rhizoma in Xiaoer Zhike Tangjiang with standardized reference extract
    Lanlan Meng, Zheng Li, Yougen Chen, Xintong Fu, Yingtao Zhang, Hongzhu Guo
    2015, 24(7):  449-457.  DOI: 10.5246/jcps.2015.07.058
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    In this study, we developed a novel and simple HPLC-DAD method for simultaneous qualitative and quantitative determination of five major components of Glycyrrhizae Radix et Rhizoma (GRR) in Xiaoer Zhike Tangjiang (XEZKTJ) with standardized reference extract (SRE). The five analytes (liquiritin apioside, liquiritin, isoliquiritin apioside, liquirigenin and glycyrrhizic acid) were well separated with good linearity, precision, stability and repeatability. The recovery rates ranged from 95.69% to 100.80%. The content of the five compounds in 34 batches of commercial XEZKTJ products was determined using standardized GRR extract (SRE method) and individual chemical reference standards (CRS method). Highly similar results were obtained from the two methods, demonstrating the feasibility of the proposed SRE method. Taken together, we proposed an efficient and low-cost way to perform multi-component quality control of XEZKTJ in this study.

    A high-performance liquid chromatography with fluorescence detection method for the simultaneous quantitation of monoamine neurotransmitters and their metabolites in subregions of rat brain
    Peng Xu, Yanping Bai, Haisong Yang, Jing Li, Wei Lu, Xiaomei Ling
    2015, 24(7):  458-466.  DOI: 10.5246/jcps.2015.07.059
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    In the present study, wesimultaneously quantified the levels of monoamine neurotransmitters (MANTs) and their metabolites (levodopa, norepinephrine, epinephrine, dopamine, 5-HT, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindole-3-acetic acid) in different brain subregions of rats using a newly developed simple, sensitive and selective high-performance liquid chromatography with fluorescence detection (HPLC-FLD) method. In this new HPLC-FLD method, analytes were directly extracted and separated without deriveatization step within 20 min. The FLD wavelength was set at 280 nm and 330 nm for excitation and emission, respectively. The analytes were separated on an Agilent Eclipse Plus C18 column (4.6 mm×150 mm, 5.0 μm) equipped with an Agilent XDB-C18 security guard column (4.6 mm×12.5 mm, 5.0 μm), and the column temperature was maintained at 35 ºC. The mobile phase for elution was isocratic. The mobile phase consisted of citric acid buffer (50 mmol/L citric acid, 50 mmol/L sodium acetate, 0.5 mmol/L octane sulfonic acid sodium salt, 0.5 mmol/L Na2EDTA and 5 mmol/L triethylamine, pH 3.8) and methanol (90:10, v/v) at a flow rate of 1.0 mL/min. The detection limit (DL) was 0.9–23 nM for all the MANTs and their metabolites with a sample volume of 50 μL. The method was shown to be highly reproducible in terms of peak area (intraday, 0.08%–1.85% RSD, n = 5). The simultaneous measurement of these MANTs and their metabolites improved our understanding of the neurochemistry in the central nervous system (CNS) in relation to different addictive drugs (methamphetamine, heroin and their mixture) in drug-addicted rat models.

    Neuroprotective effect of fucoxanthin on β-amyloid-induced cell death
    Xin Zhao, Shiping Zhang, Chunna An, Hongning Zhang, Yi Sun, Yanmei Li, Xiaoping Pu
    2015, 24(7):  467-474.  DOI: 10.5246/jcps.2015.07.060
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    Alzheimer’s disease (AD) is one of the most common cognitive disorders of the elderly. Fucoxanthin is a carotenoid that is found in common edible seaweed, and it is considered as a major active compound of marine algae with cancer-preventing,antioxidant and anti-inflammatory properties. In this study, we investigated the ability of fucoxanthin to protect against theβ-amyloid protein (Aβ)-induced neurotoxicity in primary cortical cultured neurons and PC12 cells. Neuroprotective effects of fucoxanthin were determined by measuring cell viability and nuclei double-staining with Hoechst 33342 and propidium iodide following Aβ treatment with or without fucoxanthin. Moreover, we also evaluated its potential mechanism on antioxidation by detecting the total antioxidant capacity (T-AOC), level of lipid peroxidation malondialdehyde (MDA) and activity of superoxide dismutase (SOD). We found that exposure of cortical cultured neurons or PC12 cells to Aβ resulted in neuronal cell death, whereas pre-treatment with fucoxanthin reduced Aβ-induced cell death. The data on the T-AOC, MDA level and SOD activity showed that Aβ treatment resulted in decreases in T-AOC and SOD activity and an increase in MDA level. After fucoxanthin administration, the results of T-AOC, MDA level and SOD activity showed an opposite trend, indicating that T-AOC was increased and MDA level was reduced. These results suggested that fucoxanthin prevented Aβ-induced neurotoxicity through attenuating oxidative stress induced by Aβ. Therefore, fucoxanthin might be useful as a potential preventive or therapeutic agent for AD.

    Short communications
    Simultaneous determination of ginsenosides Rg1, Re and Rb1 in rat plasma by HPLC and its application to pharmacokinetic study of SHENMAI injection
    Qingdan Xue, Peng Wang, Yuhong Kang, Qiuhong Li
    2015, 24(7):  475-481.  DOI: 10.5246/jcps.2015.07.061
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    In the present study, we developed a sensitive and efficient high performance liquid chromatography (HPLC) method for the simultaneous determination of three ginsenosides (Rg1, Re, Rb1) in rat plasma. Chromatographic separation was performed on a C18 (150 mm×4.6 mm) column utilizing gradient elution profile and a mobile phase consisting of (A) water and (B) acetonitrile. The calibration curve, with a great correlation coefficient greater than 0.998, was linear over the range of 1.0–30.0 μg/mL for ginsenoside Rg1, 0.5–15.0 μg/mL for ginsenoside Re, and 0.5–200.0 μg/mL for ginsenoside Rb1. The intra- and inter-day precisions for three ginsenosides (Rg1, Re, Rb1) were all less than 6.0%, and average recovery, examined at three concentration levels, ranged from 96.1% to 118.6%. The samples was stable within 24 h at 4 ºC storage, and 30 d at –20 ºC storage with three freeze-thaw-assay cycles. The low limits of quantification (LOQ) were 1.0, 0.5 and 0.5 μg/mL for Rg1,Re and Rb1, respectively. Taken together, the newly developed method was successfully applied to study the pharmacokinetics of ginsenoside Rg1, Re and Rb1 in rat plasma after intravenous administration of SHENMAI injection (SMI).

    Study on salary level of medical doctors in county-level public hospitals and related influencing factors
    Tiantian Hou, Yanqing Wang, Rui Tian, Guangpeng Zhang
    2015, 24(7):  482-486.  DOI: 10.5246/jcps.2015.07.062
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    This study aimed to investigate the salary status of medical doctors who work in county-level hospitals, and analyze the existing problems. Wecollected the data from questionnaires and applied both EXCEL and SPSS to conduct analysis.Doctors working in county level-hospitals received relatively lower salaries, with 78.5% of the doctors making lower than 5000 RMB per month. Influencing factors for the salary levels included personal factors, attributes of the hospitals, workload and performance appraisal.Reasonableadjustment for the salary levels is needed to refine important elements of salary distribution, and to construct a rational performance appraisal system.