CRYSTAL GROWTH & DESIGN
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2020
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IF 4.089
Chunyang Guo,Qi Zhang,Bingqing Zhu,Zaiyong Zhang,Junjie Bao,Qiaoce Ding,Guobin Ren,Xuefeng Mei
Nicorandil (NCD) is a chemically unstable drug and sensitive to humidity, heat, and mechanical stress in manufacturing processes. In this work, the cocrystals of NCD with organic acids were designed and synthesized to enhance the stability of NCD. Cocrystals of NCD with 1-hydroxy-2-naphthoic acid, salicylic acid, 3-hydroxybenzoic acid, and 2,5-dihydroxybenzoic acid were obtained. Hydrothermal stability study showed that cocrystals performed with remarkable stability advantages compared with pure NCD. On the basis of mechanism research, the stability improvements of NCD molecules can be attributed to the realignments of NCD molecules in cocrystals. After the formation of cocrystals, the novel packing styles of NCD break the self-catalyzed decomposition process in pure NCD structure. Moreover, intrinsic dissolution rate characterizations showed that the formation of cocrystals could also optimize the dissolution behavior of NCD to realize the objective of sustained release.
研究领域:
药学
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材料科学
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DOI
高影响因子
Bio-Design and Manufacturing
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2020
·Vol. 4
·期 1
·72-86
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IF 4.095
Xing Zheng,Zhao Chen,Zhang Chunchen,Fan Yubo,Liu Haifeng
For the surgical treatment of cardiovascular disease (CVD), there is a clear and unmet need in developing small-diameter (diameter < 6 mm) vascular grafts. In our previous work, sulfated silk fibroin (SF) was successfully fabricated as a potential candidate for preparing vascular grafts due to the great cytocompatibility and hemocompatibility. However, vascular graft with single layer is difficult to adapt to the complex internal environment. In this work, polycaprolactone (PCL) and sulfated SF were used to fabricate bilayer vascular graft (BLVG) to mimic the structure of natural blood vessels. To enhance the biological activity of BLVG, nicorandil (NIC), an FDA-approved drug with multi-bioactivity, was loaded in the BLVG to fabricate NIC-loaded BLVG. The morphology, chemical composition and mechanical properties of NIC-loaded BLVG were assessed. The results showed that the bilayer structure of NIC-loaded BLVG endowed the graft with a biphasic drug release behavior. The in vitro studies indicated that NIC-loaded BLVG could significantly increase the proliferation, migration and antioxidation capability of endothelial cells (ECs). Moreover, we found that the potential biological mechanism was the activation of PI3K/AKT/eNOS signaling pathway. Overall, the results effectively demonstrated that NIC-loaded BLVG had a promising in vitro performance as a functional small-diameter vascular graft.
研究领域:
生物医学工程
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心血管疾病
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组织工程
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产品关联
DOI
高影响因子
Journal of Inflammation Research
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2025
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IF 4.1
Mingyang Gu,Jiongbo Xu,Zhihan Liao,Jinhai Lin,Rui Li,Wei Wu,Yijun Qiu
Purpose: Modulation of the AKT signaling pathway can effectively regulate endoplasmic reticulum stress (ERS) and inhibit ischemia-induced cardiomyocyte apoptosis in myocardial ischemia-reperfusion injury (MIRI). The present study was designed to investigate the role of AKT and ERS in the modulation of MIRI by Huanglian Jiedu Decoction (HLJDD) through in vitro and in vivo experiments.Methods: In vivo studies employed a rat model of MIRI with three HLJDD dosage groups and a nicorandil control group. Comprehensive evaluations were conducted, including assessments of cardiac function, histopathological analysis, apoptosis detection, and immunohistochemical examination of ERS markers. For in vitro validation, H9c2 cardiomyocytes were subjected to hypoxia/reoxygenation conditions, and cellular viability assays were combined with ultrastructural and molecular analyses. Investigations guided by network pharmacology focused on the PERK/eIF2α/CHOP signaling pathway and AKT phosphorylation.Results: HLJDD demonstrated dose-dependent cardioprotective effects through attenuation of myocardial apoptosis and ERS activation. Mechanistic studies revealed its ability to restore AKT phosphorylation and suppress the PERK/eIF2α/CHOP signaling cascade. The cardioprotective effects were abolished upon AKT inhibition, thereby confirming the specificity of this pathway.Conclusion: HLJDD may serve as a potential therapeutic candidate for ischemia-induced cardiomyocyte apoptosis during MIRI. HLJDD exerts its effects by inhibiting the AKT-mediated PERK/eIF2α/CHOP signaling pathway, attenuating ERS and thereby reducing MIRI-induced apoptosis.
研究领域:
心血管药理学
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中医药学
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分子生物学
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细胞信号传导
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2022
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IF 16.744
Mengtong Xia,Yu Yan,Haiyan Pu,Xuening Du,Jingyi Liang,Yaning Sun,Jiani Zheng,Yue Yuan
In photodynamic therapy (PDT), the concentration of reactive oxygen species (ROS) generated in cells directly determines the therapeutic effect. However, excessive glutathione (GSH) concentration at the tumor site and hypoxic environment strongly reduce the production of ROS. Nitric oxide (NO) has a variety of anti-tumor activities, including the induction of cell apoptosis and sensitization to PDT, so it is in the spotlight in the area of cancer intervention. Therefore, it is very innovative to combine NO therapy with PDT and simultaneously reduce GSH content and relieve hypoxia. Metal-organic framework (MOF) is an emerging drug delivery vehicle that can exert photodynamic effects when a photosensitizer is used as its organic ligand. In this study, we constructed a GSH-responsive NO producing nanosystem to enhance ROS production through GSH depletion and hypoxia alleviation. Briefly, nicorandil (Nic) is encapsulated into porous porphyrinic MOF nanoparticles, and hyaluronic acid (HA) is electrostatically adsorbed on the surface of the MOF nanoparticles for CD44 receptor-targeting and prevention of Nic leakage. Notably, the Nic reacts with GSH to produce NO gas with vasodilation and GSH reduction, thus improving oxygen supply for efficient ROS generation. Moreover, the generated NO can further react with superoxide radical anion to produce highly reactive peroxynitrite (ONOO − ) molecules with higher cytotoxicity. Overall, the [email protected] nanosystem combines NO gas therapy with PDT, resulting in a significant increase in ROS production and greatly enhancing the efficacy of PDT.
研究领域:
癌症治疗
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药物递送系统
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材料科学
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生物化学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）