INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2020
·
IF 4.845
Yang Gao,Guangli Liao,Shucong Wang,Ya Sun,Xin Long,Yan Ma,Hailong Zhang
This research aims to investigate the potential of N-[4-[1-(3-Aminopropyl)-2-hydroxy-2-nitrosohydrazino]butyl]-1,3-propanediamine (SPM-NONOate) for promoting the absorption of poorly absorbed macromolecules delivered by intrapulmonary route. Influence of SPM-NONOate on the drug absorption was characterized by using a series of fluorescein isothiocyanate-labeled dextrans (FDs) as affordable models of hydrophilic macromolecules with established tools for quantitative analysis. SPM-NONOate increased concentration-dependently within 1–10 mM the pulmonary absorptions of FDs in rats. Moreover, this promoting effect varied with the molecular weight of FDs, and the largest absorption enhancement effect was obtained for FD70. SPM-NONOate also showed promising enhancement potential on the absorption of some therapeutic peptides, where obvious hypoglycemic and hypocalcemic effects were observed after intrapulmonary delivery of insulin and calcitionin, respectively, with SPM-NONOate to rats. The safety of SPM-NONOate was confirmed based on measurement of some biological markers in bronchoalveolar lavage fluid (BALF) of rats. Additionally, mechanism underling the absorption enhancement action of SPM-NONOate was explored by combinatorial administration of FD4 and SPM-NONOate with various scavengers and generator to rat lungs. Results indicated that NO released from SPM-NONOate induced the enhancement in the drug absorption, and peroxynitrate , a NO metabolite, possibly participated in the absorption enhancing action of SPM-NONOate.
研究领域:
药理学
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药物递送系统
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生物化学
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DOI
PubMed
高影响因子
LANGMUIR
·
2020
·
IF 3.557
Tianyu Zhu,Min Zhou,Wentao Gao,Dan Fang,Zhiyong Liu,Guangyan Wu,Mimi Wan,Chun Mao,Jian Shen
In the treatment of coronary artery disease (CAD), the use of stent implantation often leads to clinical complications such as restenosis, delayed endothelial healing, and thrombosis. Here, we develop a double drug sustained-release coating for the stent surface by grafting heparin/NONOate nanoparticles (Hep/NONOates). The Hep/NONOates and surface modification of the stent were characterized by X-ray photoelectron spectroscopy, attenuated total reflection Fourier-transform infrared spectroscopy, static water contact angle, and scanning electron microscopy (SEM), and the release behaviors of the anticoagulant, heparin (Hep) and the bioactive molecule, nitric oxide (NO) were studied. Furthermore, the blood compatibility and cytotoxicity of the modified stent were evaluated by whole blood adhesion and platelet adhesion tests, hemolysis assay, morphological changes of red blood cells, plasma recalcification time assay, in vitro coagulation time tests, and MTT assay. Finally, the results of a rabbit carotid artery stent implantation experiment showed that the double drug sustained-release coating for the stent can accelerate regeneration of endothelial cells and keep good anticoagulant activity. This study can provide new design ideas based on nanotechnology for improving the safety and effectiveness of drug-eluting stents.
研究领域:
心脏病学
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纳米技术
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生物材料
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
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2023
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IF 3.9
Weihang Zhang,Bin Chen,Run Lin,Haitao Dai,Yan Zhang,Mao Qunlong,Yonghui Huang
Objectives The aim of this study was to synthesize and characterize a novel NO donor, PEI-PO-NONOate, using propylene oxide and to investigate its biosafety and therapeutic efficacy via nasal administration in vitro and vivo. Experimental procedures The PEI-PO-NONOate was synthesized based on polyethylenimine (PEI) with different molecular weights and characterized using Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR), and ultraviolet (UV) spectroscopy. Cytotoxicity assays were performed on mouse fibroblast cells L929 and human nasal mucosa epithelial cells (HNEpC), and a rat middle cerebral artery occlusion (MCAO) model was established to evaluate the therapeutic efficacy of PEI-PO-NONOate via nasal administration. Results The PEI-PO-NONOate was found to be stable under dark, dry, and airproof conditions, and its release was accelerated in an aqueous phase or acidic environment, while it was slowed down in a polyethylene glycol (PEG) mixture system. The NO donor released approximately 0.4, 0.5, and 0.6 μmol of gaseous NO from 1.0 mg of the polymer based on PEI600, PEI1800, and PEI10K, respectively. Cytotoxicity assays showed that the PEI-PO-NONOates had a cryoprotective effect as compared with PEI and PEI-PO. Furthermore, nasal administration of PEI-PO-NONOates resulted in a significant reduction in overall necrotic ratio as compared with the control group (16.4% versus 24.6%, p < 0.05). Conclusion The findings of this study suggest that PEI-PO-NONOates may have potential as an adjuvant therapy for acute ischemic stroke when administered via the nasal route.
研究领域:
药理学
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神经科学
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Anti-Cancer Agents in Medicinal Chemistry
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2024
·Vol. 24
·期 15
·1142-1150
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IF 2.6
Wang Mingdong,Yin Jizhong,Han Qianyu,Li Bing,Zhao Xue-Wei,Xue Lei
Background: Non-Small Cell Lung Cancer (NSCLC) ranks as a leading cause of cancer-related mortality, necessitating the urgent search for cost-effective and efficient anti-NSCLC drugs. Our preliminary research has demonstrated that arsenic trioxide (ATO) significantly inhibits NSCLC
angiogenesis, exerting anti-tumor effects. In conjunction with existing literature reports, the Nrf2-IL-33 pathway is emerging as a novel mechanism in NSCLC angiogenesis. Objective: This study aimed to elucidate whether ATO can inhibit NSCLC angiogenesis through the Nrf2-IL-33 pathway.
Methods: Immunohistochemistry was employed to assess the expression of Nrf2, IL-33, and CD31 in tumor tissues from patients with NSCLC. DETA-NONOate was used as a nitric oxide (NO) donor to mimic high levels of NO in the tumor microenvironment. Western blot, quantitative real-time PCR,
and enzyme-linked immunosorbent assay were utilized to evaluate the expression of Nrf2 and IL-33 in the NCI-H1299 cell line. Subcutaneous xenograft models were established in nude mice by implanting NCI-H1299 cells to assess the anti-tumor efficacy of ATO. Results: High expression levels
of Nrf2 and IL-33 were observed in tumor samples from patients with NSCLC, and Nrf2 expression positively correlated with microvascular density in NSCLC. In vitro, NO (released from 1mM DETA-NONOate) promoted activation of the Nrf2-IL-33 signaling pathway in NCI-H1299 cells, which was
reversed by ATO. Additionally, both Nrf2 deficiency and ATO treatment significantly attenuated NOinduced IL-33 expression. In vivo, both ATO and the Nrf2 inhibitor ML385 demonstrated significant inhibitory effects on angiogenesis tumor growth. Conclusion: Nrf2-IL-33 signaling is
usually activated in NSCLC and positively correlates with tumor angiogenesis. ATO effectively disrupts the activation of the Nrf2-IL-33 pathway in NSCLC and thus inhibits angiogenesis, suggesting its potential as an anti-angiogenic agent for use in the treatment of NSCLC.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Polymeric Materials and Polymeric Biomaterials
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2021
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IF 2.604
Ziheng Chen,Song Peng,Shixin Liu,Chengpeng Li,Xiang Cai,Dong Ma,Wu Zhang
Bacterial infection is a serious threat to human health. In this work, carbon dots (CDs) based on the polyethyleneimine (PEI) was prepared by hydrothermal carbonization method and then reacted with nitric oxide (NO) to form the NO-loaded CDs (CD-PEI/NONOate). CD-PEI/NONOate showed a high NO payload and outstanding fluorescence characteristics. It was found that CD-PEI/NONOate could inhibit the growth of Gram-negative bacteria Pseudomonas aeruginosa by more than 99%. Moreover, CD-PEI/NONOate showed no cytotoxicity to 3T3 cells at concentrations used in vitro. These results indicated that the prepared CD-PEI/NONOate has a potential application in the diagnosis and treatment of bacterial infection.
研究领域:
材料科学
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微生物学
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生物医学工程
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Ding Wang,Yaoqing Chu,Shuiping Liu,Lianjiang Tan
Vessel normalization has proved imperative in tumor growth inhibition. In this work, biopolymer-based hybrid nanospheres capable of normalizing blood vessels were designed to improve the therapeutic effect of chemotherapeutic drugs. Zn 0.4 Fe 2.6 O 4 nanoparticles (ZFO NPs) were synthesized, and were encapsulated in cross-inked chitosan (CS) along with a nitric oxide (NO) precursor, DETA NONOate, forming hybrid ZFO/NO@CS nanospheres highly stable in physiological environment. The structure, morphology and size of the nanospheres were characterized. The ZFO/NO@CS nanospheres could release NO under acidic conditions typical of intratumoral and intracellular environment. The results of related factors expression, wound healing and tube formation assays demonstrated that both the encapsulated ZFO NPs and the released NO were able to inhibit angiogenesis in tumors. The ZFO/NO@CS nanospheres enhanced the antitumor efficacy of the chemotherapeutic drug DOX by normalizing tumor vessels, as evidenced by in vivo experiments for CT26 tumor-bearing mice. By analyzing the contents of Fe in the tumor and different organs, the nanospheres were found to accumulate primarily at the tumor site. The blood analysis showed little side effect of the nanospheres. The ZFO/NO@CS nanospheres have great potential in improving tumor therapeutic effect when used in combination with chemotherapeutic drugs.
研究领域:
纳米技术
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癌症研究
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Research
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2024
·
IF 8.1
Ding Wang,Cheng-Jie Qiu,Yaoqing Chu,Anzhuo Zhang,Ran Huang,Si-Jian Pan,Lianjiang Tan
Lung cancer remains a great threat to human health despite the rapid development of various therapeutic methods. Chemotherapy continues to be the most commonly employed treatment for lung cancer; however, it often suffers from low drug delivery efficiency and severe side effects. To enhance the therapeutic efficacy of chemotherapy, we developed a novel strategy that integrates tumor vasculature normalization with the co-delivery of therapeutic agents. This strategy employs a diblock polymeric vesicle with a reduction-sensitive linkage. Paclitaxel (PTX) is encapsulated in the bilayer, while an acid-sensitive nitric oxide (NO) precursor, DETA NONOate, and zinc oxide nanoparticles (ZnO NPs) are loaded into the central cavity. The resulting nanosystem, (ZnO,NONO)@Ves-PTX, is designed to release NO under the acidic conditions typical of the tumor microenvironment (TME) and intracellular environment. The released NO in the TME inhibits angiogenesis, thereby facilitating the delivery and distribution of therapeutic agents. Upon internalization by tumor cells, (ZnO,NONO)@Ves-PTX decomposes in response to intracellular glutathione (GSH), releasing the loaded agents. DETA NONOate and ZnO NPs generate NO and Zn2+ ions, respectively, at the intracellular pH, which synergistically inhibit tumor growth alongside PTX. This combined therapeutic approach demonstrated remarkable potential in improving the chemotherapeutic efficacy for lung cancer, offering a promising direction for future cancer treatments.
研究领域:
肿瘤学
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药理学
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纳米技术
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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2018
·Vol. 28
·期 20
·1707440
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IF 13.325
Siming Yu,Guowei Li,Rui Liu,Dong Ma,Wei Xue
Nowadays, antibiotic abuse increases the emergence of multidrug-resistant bacterial strains, which is the major reason for the failure of conventional antibiotic therapies. Therefore, developing novel antibacterial materials or therapies is an urgent demand. In the present study, photothermal and NO-releasing properties are integrated into a single nanocomposite to realize more efficient bactericidal effects. To this end, polydopamine (PDA) coated iron oxide nanocomposite (Fe 3 O 4 @PDA) is used as a photoconversion agent and the core, first three generation dendritic poly(amidoamine) (PAMAM-G3) is grafted on the surface of Fe 3 O 4 @PDA, and subsequently NO is loaded with the formation of NONOate. The resultant Fe 3 O 4 @PDA@PAMAM@NONOate displays controllable NO release property under intermittent 808 nm laser irradiation and excellent bacteria-separation efficiency. Moreover, excellent synergistic photothermal and NO antibacterial effects are observed against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus , where bacterial viability and biofilm are significantly reduced. An antibacterial mechanism study reveals that the materials first adsorb onto the bacterial membrane, then cause damage to the membrane by the increased local temperature and the released NO under laser irradiation conditions, finally leak the intracellular components like DNA and induce bacteria death. The work provides a novel way for designing of antibacterial materials with higher efficiency.
研究领域:
材料科学
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纳米技术
·
细菌学
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治疗学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）