JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2018
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IF 1.911
Yongli Shi,Jintao Xue,Zhaojie Liu,Mengjiao Du,Lanting Xu,Qianqian Sun,Zhaomin Liu,Qing Shang
In this study, a novel chitosan (CS)-modified nanoparticles (NPs) were developed to orally deliver tolbutamide (TOL). Methoxy poly(ethylene glycol)- b-poly(ε-caprolactone) carboxylates (mPEG2000-b-PCL4000) was synthesized via an esterification reaction. CS-modified mPEG2000-b-PCL4000-COOH NPs (CS@NPs) were fabricated by injecting mPEG2000-b-PCL4000-COOH NPs suspension (1.0 mg/mL) into CS solution (1.0 mg/mL, pH 5.0). Fourier transform infrared spectroscopy (FTIR) spectra were used to confirm the obtaining of mPEG2000-b-PCL4000-COOH. Transmission electron microscope (TEM) was carried out to observe morphology of all NPs. Nano ZS90 Malvern ParticleSizer were used to monitor the size distribution of obtained NPs. Thermogravimetry analysis (TGA) was performed to investigate the thermostability of CS@NPs. In vitro TOL release profiles were carried out in pH 1.2 and 7.4 buffers. FTIR spectra confirmed the obtaining of mPEG2000-b-PCL4000-COOH. TGA curves indicated that the protection of CS shells improved the thermostability of mPEG2000-b-PCL4000-COOH NPs. Cell tests indicated the CS@NPs had no obvious cytotoxicity, and they were easily taken up by 293T cells. In vitro release profiles showed that 91.0 ± 1.9% of encapsulated TOL were released from TOL-CS@NPs in pH 7.4 buffer. Therefore, the positive potential of CS@NPs could increase their combining capacity with intestinal mucosal cells. Finally, these NPs would improve the bioavailability of hydrophobic drugs.
研究领域:
药剂学
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生物材料
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
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2021
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IF 6.165
Lei Yuan,Zidan Cao,Renren Sun,Haixia He,Yiming Ren,Huimin Niu,Tao Li,Baozeng Ren
A novel antiepileptic drug of topiramate (TPM) has remarkably boosted the human health to against epilepsy. Herein, the solubility of TPM was measured in fourteen mono-solvents through a method of laser monitoring at temperatures from 278.15 to 323.15 K in this work. Moreover, the electrostatic potential surfaces and quantum chemistry calculation at molecular level were applied to explain the solubility differences. The multiple factors such as the polarity of solvent, active sites interaction, the molecular size and free volume all affect the solubility of TPM. Not only the solubility data of TPM were obtained, but also the thermodynamic properties of TPM in various solvents were studied. The solid–liquid phase equilibrium solubility of TPM was regressed and corrected by five thermodynamic models including λ-h, NRTL, NRTL-SAC, UNIQUAC models and modified Apelblat equation, and the classical van't Hoff equation was employed to analyze the thermodynamic properties during the process of TPM dissolution. This research will provide basic data for the production of TPM in the pharmaceutical industry.
研究领域:
药物化学
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物理化学
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热力学
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分子模拟
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产品关联
DOI
高影响因子
PHYTOMEDICINE
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2023
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IF 7.9
Chao Ma,Chunran Zhu,Yajun Zhang,Mei Yu,Yizhi Song,Yulong Chong,Yan Yang,Chan Zhu,Yucui Jiang,Changming Wang,Shuo Cheng,Keke Jia,Guang Yu,Jia Li,Zongxiang Tang
Background Increasing evidence highlights the involvement of metabolic disorder and calcium influx mediated by transient receptor potential channels in migraine; however, the relationship between these factors in the pathophysiology of migraine remains unknown. Gastrodin is the major component of the traditional Chinese medicine Tianma, which is extensively used in migraine therapy. Purpose Our work aimed to explore the analgesic action of gastrodin and its regulatory mechanisms from a metabolic perspective. Methods/results After being treated with gastrodin, the mice were given nitroglycerin (NTG) to induce migraine. Gastrodin treatment significantly raised the threshold of sensitivity in response to both mechanical and thermal stimulus evidenced by von Frey and hot plate tests, respectively, and decreased total contact numbers in orofacial operant behavioral assessment. We found that the expression of transient receptor potential melastatin 2 (TRPM2) channel was increased in the trigeminal ganglion (TG) of NTG-induced mice, resulting in a sustained Ca 2+ influx to trigger migraine pain. The content of succinate, a metabolic biomarker, was elevated in blood samples of migraineurs, as well as in the serum and TG tissue from NTG-induced migraine mice. Calcium imaging assay indicated that succinate insult elevated TRPM2-mediated calcium flux signal in TG neurons. Mechanistically, accumulated succinate upregulated hypoxia inducible factor-1α (HIF-1α) expression and promoted its translocation into nucleus, where HIF-1α enhanced TRPM2 expression through transcriptional induction in TG neurons, evidenced by luciferase reporter measurement. Gastrodin treatment inhibited TRPM2 expression and TRPM2-dependent Ca 2+ influx by attenuating succinate accumulation and downstream HIF-1α signaling, and thereby exhibited analgesic effect. Conclusion This work revealed that succinate was a critical metabolic signaling molecule and the key mediator of migraine pain through triggering TRPM2-mediated calcium overload. Gastrodin alleviated NTG-induced migraine-like pain via inhibiting succinate/HIF-1α/TRPM2 signaling pathway in TG neurons. These findings uncovered the anti-migraine effect of gastrodin and its regulatory mechanisms from a metabolic perspective and provided a novel theoretical basis for the analgesic action of gastrodin.
研究领域:
神经科学
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药理学
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代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）