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Table of Content

    04 September 2018, Volume 27 Issue 8
    Original articles
    Treatment of cervical cancer by siRNA-loaded chitosan-coated calcium phosphate nanoparticles
    Piaopiao Li, Yi Yan, Haitao Zhang, Ru Wang, Huhu Han, Jiancheng Wang
    2018, 27(8):  517-529.  DOI: 10.5246/jcps.2018.08.053
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    In the present study, a chitosan-coated calcium phosphate nanoparticle (CS/CaP/siRNA NP) was developed to deliver siRNA for treatment of cervical cancer. The CS/CaP/siRNA NPs were prepared by the nano-precipitation method. The resulted NPs had a uniform spherical morphology with a size of ~194 nm and a zeta potential of ~+27 mV. In vitro experiments demonstrated that these NPs could efficiently deliver siEGFR into Hela cells and significantly down-regulate the EGFR expression level, which was probably associated with enhanced cell adhesion of chitosan, leading to extended residence time of cell internalization. Then the internalized CS/CaP/siRNA NPs exhibited pH-responsive disassembly of NPs, resulting in the enhanced release of siRNA and rapid lysosomal escape into cytoplasm. Moreover, in vivo anticancer results showed that the CS/CaP/siRNA NPs had significant inhibitory effects on tumor growth after intratumoral injection in Hela tumor xenografted nude mice, accompanying with no obvious changes of body weight during the whole experimental period. All these results indicated that the CS/CaP/siRNA NPs would have great potential to deliver siRNA for the treatment of cervical cancer via mucosal administration.

    Preparation and characterization of dual pH-sensitive polymer-doxorubicin conjugate micelles
    Yang Zou, Yao Jin, Yuanhang Zhou, Chuyu He, Yunqiang Deng, Shidi Han, Chuhang Zhou, Xinru Li, Yanxia Zhou, Yan Liu
    2018, 27(8):  530-539.  DOI: 10.5246/jcps.2018.08.054
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    In the present study, we designed and fabricated pH-sensitive polymeric micelles based on the conjugate of poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) (PEOz-PLA) with doxorubicin (PEOz-PLA-imi-DOX) to efficiently inhibit tumor cell growth. Hence, PEOz-PLA-imi-DOX was successfully synthesized by connecting DOX to the hydrophobic end of pH-sensitive PEOz-PLAvia acid cleavable benzoic imine linker and characterized by 1H NMR spectrum and thin layer chromatography. The critical micelle concentration of PEOz-PLA-imi-DOX was determined to be (14.84±3.85) mg/L. The conjugate micelles (denoted as PP-DOX-PM) formed by PEOz-PLA-imi-DOX using film-hydration method were characterized to have a nano-scaled size of about 21 nm in diameter, and the drug loading content was 1.67%. PP-DOX-PM showed pH-dependent drug release behavior with gradually accelerated release of DOX with decrease of pH value, illustrating the micelles’ distinguishing feature of endo/lysosomal pH from physiological pH by accelerating drug release. As anticipated, PP-DOX-PM maintained the cytotoxicity of DOX against MDA-MB-231 cells. Collectively, PP-DOX-PM might have great potential for effective suppression of tumor growth. 

    The design, synthesis and α7 nicotinic acetylcholine receptors positive allosteric modulative evaluation of 3H-quinazolin-4-one derivatives
    Zongze Huang, Xintong Wang, Ying Meng, Xin Li, Haoran Xiao, Xiling Bian, KeWei Wang, Qi Sun
    2018, 27(8):  540-552.  DOI: 10.5246/jcps.2018.08.055
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    A series of new 6-substituted 3H-quinazolin-4-ones (3a3d) were designed, synthesized and evaluated as the type I positive allosteric modulators (PAMs) of human α7 nAChR expressed in Xenopus ooctyes by two-electrode voltage clamp. However, no compound showed a better efficacious PAM than lead compound 2 in the presence of acetylcholine (100 μM). The structure-activity relationship (SAR) analysis suggested that thiazolo[4,5-d]pyrimidin-7(6H)-one was the key biological skeleton. 

    Lanthanum chloride or citrate is absorbed mainly via M cells in gastrointestinal tracts with lanthanum phosphates as the transformed species
    Huixia Huang, Huixue Liu, Xiaojie Ma, Hui Guan, Xiaogai Yang
    2018, 27(8):  553-564.  DOI: 10.5246/jcps.2018.08.056
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    工作以氯化镧(LaCl3)和柠檬酸镧(LaCit)为代表性化合物, 对稀土在消化道内的物种存在形式及吸收转运机制进行了研究和探讨。研究采用了人工胃液和肠液模拟体内消化道环境。电感耦合等离子体质谱(ICP-MS)检测结果表明, 大于99.9%La发生了沉淀。散射光粒度(DLS)分析结果显示, 这些微粒的平均粒径由200 nm (孵育2 h)增大到600 nm左右(孵育24 h), 这表明微粒之间发生了聚集。傅立叶变换红外光谱(FTIR)研究表明, 稀土微粒的主要成分为稀土磷酸盐。为研究稀土在肠道中的吸收转运机制, LaCit (2100 mg/kg/day)对小鼠灌胃给药7, 取小肠的普通肠段和派氏结进行了ICP-MS分析。派氏结中的La含量明显高于普通肠段, 这提示稀土微粒可能主要由派氏结上淋巴滤泡上皮中M细胞吞噬转运。此外, 建立了Caco-2细胞单培养模型和 Caco-2/Raji B 细胞共培养模型分别模拟小肠上皮和滤泡上。结果显示, Caco-2/Raji B 细胞共培养模型转运的La含量显著高于Caco-2细胞单培养模型(大约60倍左右), Caco-2 细胞单层透过的镧的量极低, 这说明M细胞是吸收转运磷酸镧的主要途径。以上结果表明氯化镧和柠檬酸镧在胃肠道主要以磷酸镧微粒形式通过M细胞进行转运吸收。本研究将为稀土在农业和医学中的合理应用提供科学依据。

    Paeonol attenuates progression of atherosclerotic lesion formation through lipid regulation, anti-inflammatory and antioxidant activities
    Aiwei Song, Hongfei Wu, Min Dai
    2018, 27(8):  565-575.  DOI: 10.5246/jcps.2018.08.057
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    As an active component extracted from Chinese herb moutan cortex and roots of paeonia lactiflora pallas, paeonol possesses many biological activities, including anti-inflammatory and vascular protection activities. In this study, athero-protectiveeffects of paeonol were investigated in apoliprotein E deficient (ApoE–/–) mice through the entire course of atherosclerotic development. ApoE–/– mice were divided into five groups and fed a high-cholesterol diet (HCD) for 5, 15 and 25 weeks. Then they were fed either paeonol or atorvastatin for 6 weeks. The methods, such as ELISA for serum lipid and cytokine analyses, Western blotting for protein expressions, and H&E and oil-red o-staining method, were used for evaluation of thoracic aorta lesion area. The results showed that paeonol could significantly reduce body weight, blood lipid, total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL-C) in ApoE–/– mice at all stages of the atherosclerosis process. Paeonol also reduced the levels of anti-inflammation factors, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, oxidized LDL cholesterol (ox-LDL), in serum. In paeonol groups, SOD was significantly increased, whereas MDA was decreased compared with the HCD group (P<0.01). Paeonol markedly attenuated the thickness of the lipid-rich plaque and down-regulated the expressions of VCAM-1 and MMP-9 in aorta of mice, suggesting that paeonol could inhibit formation of plaque and stabilize plaques. Taken together, paeonol appeared to have anti-dyslipidemia and anti-atherosclerotic effects by lipid regulation, and it could inhibit the effects of inflammation and oxidative stress on HCD-fed ApoE–/– mice through the entire course of atherosclerotic development.

    Sesquiterpenes from Artemisia giraldii var. longipedunculata
    Yang Xue, Chen Zhang, Zhibo Wu, Puming Zhang, Mingbo Zhao, Yong Jiang, Pengfei Tu
    2018, 27(8):  576-581.  DOI: 10.5246/jcps.2018.08.058
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    A phytochemical investigation on the aerial parts of Artemisia giraldii var. longipedunculata led to the isolation of 10 known sesquiterpenes, including12-hydroxy-α-cyperone (1), 1β,6α-dihydroxyeudesma-4(15)-ene (2), carainterol A (3), oplodiol (4),douglanin (5), 1α-hydroxyisodauc-4-en-15-al (6), 3α,6α-dihydroxybisabola-4,10-diene (7), 4α,5β-dihydroxybisabola-2,10-diene(8), opposit-4(15)-ene-1β,7-diol (9), and saniculamoid D (10), respectively. Their structures were elucidated by analysis of the MS and NMR spectroscopic data and comparison with the literature. All the isolates were obtained from A. giraldii var. longipedunculata for the first time, and five of them were obtained from the genus Artemisia for the first time. Additionally, the 13C NMR data of 1 were fully assigned based on the 2D NMR data for the first time.

    Drug administration and clinical pharmacy column
    Research on the sharing mechanism of drug price information in China- from the perspective of intergovernmental information sharing
    Shuai Wang, Ting Yin, Ningtai Luo, Xiaoping Liu, Bin Jiang
    2018, 27(8):  582-587.  DOI: 10.5246/jcps.2018.08.059
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    Establishment of sharing mechanism for drug price information to guarantee the construction of a unified cross-departmental price information platform is a new national policy after Chinese government abandoned drug price control. Based on the theory of intergovernmental information sharing, this study aimed to investigate the drug price information sharing mechanism in China through literature research and stakeholder interviews, which included institution guarantee mechanism, department coordination mechanism and technical support mechanism.

    Other
    Pharmaceutical College of Seoul National University signed the cooperation agreement with School of Pharmaceutical Sciences, Peking University Health Science Center
    School of Pharmaceutical Sciences, Peking University Health Science Center
    2018, 27(8):  588-588. 
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    Pharmaceutical College of Seoul National University signed the cooperation agreement with School of Pharmaceutical Sciences, Peking University Health Science Center.