INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Linyi Xu,Rou Guan,Bohong Yu,Yicheng Li,Hongzhuo Liu,Yiguo Jiang
Although deferoxamine (DFO) has been approved for the treatment the iron overloaded diseases, its clinical application is impeded by very short circulation time and its relating toxicity. In this work, the fluorene methoxycarbonyl (FMOC) for “albumin hitchhiking” was used to prolong the plasma circulation time of DFO and reduce toxicity. The designed FMOC-PEG-DFO conjugates were found to reversible bind to albumin and gradually release DFO in vivo . Herein, the FMOC-PEG 1000 -DFO conjugates could increase 30 times the blood circulation time of DFO with the improvement of the iron elimination efficacy. Meanwhile, the conjugates markedly reduced the cytotoxicity of DFO. Taken together, the result demonstrated the FMOC-PEG 1000 -DFO conjugates could be a potential therapeutic choice for iron-overload-related diseases.
研究领域:
药学
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药物递送系统
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 39
·32471-32479
·
IF 3.289
Meng Tian,Xi Chen,Hao Li,Lu Ma,Zhipeng Gu,Xin Qi,Xi Li,Hong Tan,Chao You
To address the drawbacks of deferoxamine, a clinical drug widely used for iron-overload-related conditions, oxidation-responsive alginate–deferoxamine (Alg–DFO) conjugates were prepared and their structure characterized by size-exclusion chromatography, FTIR, and 1H NMR. The prepared conjugates exhibited long-term stability, with a half-life 9.8–17.8 times longer than that of the free DFO, depending on the molecular weight of the conjugated alginate. On the other hand, the conjugates could quickly respond to oxidative stimuli and be degraded, which suggests they hold the potential to be cleared from the body in an iron-overload-related oxidative environment to avoid their accumulation and to address safety concerns. The degradation mechanism for the oxidative response is proposed. At the same time, it is interesting to find that the conjugates are capable of protecting the iron-binding capacity of the attached DFO from the oxidation environment, which probably is a result of the antioxidant activities of the conjugated alginate. In addition, the conjugates show a lower cytotoxicity in comparison with the free DFO. Overall, it is anticipated that the Alg–DFO conjugates prepared in this work will have the potential to be used for treating iron-overload-related disease.
研究领域:
生物材料学
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药物化学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Langjie Chai,Jianglong Huang,Min Wang,Yihui Huang,Zhuo Huang,Ruiyu Zhang,Lu He,Haijie Wang,Danyang Chen,Yifeng Lei,Liang Guo
In chronic third-degree burn wounds, high levels of inflammatory factors such as IL-1β lead to ferroptosis in surrounding cells, thereby delaying the healing process of the burn wounds. To promote the healing of such wounds, an injectable DFO@GM-H hydrogel was developed. This hydrogel was prepared by loading deferoxamine (DFO) into gelatin microspheres (GMs), and further crosslinking in a mild reaction. The resulting DFO@GM-H hydrogels demonstrated effective self-healing and injectability, rendering them well-suited for application in irregular burn wounds. DFO@GM-H hydrogels not only maintained a moist healing environment for the burn wound healing, but also exhibited the ability to slowly release DFO, therefore overcoming the limitation of the short half-life of DFO in vivo . With sustained release and enhanced stability of DFO from the injectable hydrogels, DFO@GM-H hydrogels demonstrated excellent biocompatibility, effectively promoted cell proliferation, migration and angiogenesis, showed antibacterial activity, and effectively inhibited cellular ferroptosis both in vitro and in vivo . Consequently, DFO@GM-H hydrogels accelerated the healing of burn wounds in rats via ferroptosis inhibition and enhanced cellular response. Therefore, DFO@GM-H hydrogel is anticipated to emerge as a novel bioactive dressing for the management of burn wounds.
研究领域:
生物材料学
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创伤修复
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2024
·
IF 5.6
Na Li,Xian Li,Xiaoe Ming,Jingyuan Chen,Yeyi Chen,Lifen Zhou,Ruirui Yao,Yuqi Yao
Deferasirox (DEF) is an important iron chelator for treatment of iron overload–related diseases. Monitoring DEF concentration in human serum will provide some valuable information for clinical diagnosis and therapy of such diseases. In this study, we developed a peroxidase-mimicking colorimetric sensor for the detection of DEF by simple assembly of a telomeric dimeric G-quadruplex DNAzyme with Cu 2+ . The DNAzyme–catalyzed oxidation of 3,3′,5,5′-tetramethylbenzidine in the presence of H 2 O 2 can generate a quantitative colorimetric signal, and the color change can be discerned by the naked eye. Compared with the reaction rate of the monomeric G-quadruplex–Cu 2+ DNAzyme, the reaction rate of the dimeric G-quadruplex–Cu 2+ (G2–Cu 2+ ) DNAzyme is significantly accelerated, and the reaction rate gradually increases and then reaches a plateau with increasing number of TTA spacers. Herein, the G2–Cu 2+ DNAzyme is chosen for the highly sensitive detection of DEF based on the DEF–Cu 2+ complex–induced inhibition of its peroxidase-mimicking activities. The limit of detection (LOD) of DEF is achieved as low as 0.03 μM, and the linear range is from 0.05 to 1.2 μM. The proposed strategy exhibits excellent selectivity in the presence of potential interferents, such as metal ions and small molecules. Importantly, the G2–Cu 2+ DNAzyme is further expanded to detect DEF in dispersible tablets and human serum samples. Overall, this G2–Cu 2+ DNAzyme provides a simple, low-cost, and rapid platform for DEF detection. This novel strategy is the first example of DEF analysis by utilizing signal amplification technology based on the G-quadruplex DNAzyme and holds great potential for DEF quality control and therapeutic drug monitoring.
研究领域:
生物化学
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医学诊断
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药物分析
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2025
·
IF 4.3
Jie Wang,Fan Yang,Ruting Chen,Xinyue Yang,Jingjing Wang,Hongyan Zhang
Fast reconstruction of the pulpal vasculature is crucial for effective pulp regeneration. Dental pulp stem cells (DPSCs) are promising candidates for pulp regeneration because of their potential for multilineage differentiation and vasculogenic properties. Deferoxamine (DFO) has been shown to stimulate angiogenesis during wound healing and bone regeneration; however, the effects of DFO on the angiogenic potential of DPSCs remain unknown. Moreover, its usefulness is restricted by a limited half-life and challenges in achieving localized tissue enrichment. This study aimed to develop a sustained-release injectable hydrogel composite as a drug delivery system and to investigate its influence on DPSCs. Herein, gelatin-based microspheres (GMSs) were loaded with DFO, and temperature-sensitive injectable hydrogels incorporating collagen and chitosan were synthesized to enable controlled DFO release. The experimental findings demonstrated that the DFO-loaded GMSs (DFO-GMSs) hydrogel composite possessed favorable physical properties and biocompatibility, enabling sustained DFO delivery for up to 15 days. DFO effectively stimulated DPSC migration, promoted the secretion of angiogenesis-related factors, and induced tube formation in vitro. These results suggest that the DFO-GMSs hydrogel composite significantly increased the migration and angiogenic potential of DPSCs, highlighting its promise for tissue regeneration applications.
研究领域:
再生医学
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生物材料科学
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口腔医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Fang Zhu,Jianhua Zhang,Jian Zhong,Tianyou Wang,Yiwen Li,Zhipeng Gu
Iron-overload diseases are characterized by a variety of symptoms resulting from excessive iron stores, oxidative stress and consequent end-organ damage. Deferoxamine (DFO) is an iron-chelator that can protect tissues from iron-induced damage. However, its application is limited due to its low stability and weak free radical scavenging ability. Herein, natural polyphenols have been employed to enhance the protective efficacy of DFO through the construction of supramolecular dynamic amphiphiles , which self-assemble into spherical nanoparticles with excellent scavenging capacity against both iron (III) and reactive oxygen species (ROS). This class of natural polyphenols-assisted nanoparticles was found to exhibit enhanced protective efficacy both in vitro in an iron-overload cell model and in vivo in an intracerebral hemorrhage model. This strategy of constructing natural polyphenols- assisted nanoparticles could benefit the treatment of iron-overload related diseases with excessive accumulation of toxic or harmful substances.
研究领域:
医学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Neurology
·
2022
·
IF 4.086
Ren Siying,Han Shanshan,Wang Likun,Huang Yuanxin,Wu Jing,Wu Guofeng
Objective: To investigate the role of minimally invasive surgery (MIS) in intracerebral hemorrhage (ICH) evacuation combined with deferoxamine (DFX) treatment on perihematomal tight junction protein (claudin-5 and ZO-1) expression levels and blood-brain barrier (BBB) permeability in rabbits.Methods: We randomly assigned 65 male rabbits (weight: 1.9–2.6 kg) to a normal control group (NC group, 13 rabbits), hemorrhage model group (HM group, 13), DFX treatment group (DFX group, 13 rabbits), MIS group (MIS group, 13 rabbits), or MIS combined with DFX treatment group (MIS + DFX group, 13 rabbits). ICH was established in all of the groups except the NC group. MIS was performed to evacuate the hematoma 6 h after the ICH model was created in the MIS and MIS + DFX groups. The DFX and MIS + DFX groups were treated with DFX (100 mg/kg, dissolved in 2 mL of 0.9% saline solution, administered intramuscularly) at 2 h, and then every 12 h for 7 d. The same dose of 0.9% saline solution was administered to the NC, HM, and MIS groups at the same time points. Sixty-five rabbits were divided into 5 groups, and 13 rabbits in each group. Neurological deficit (i.e., Purdy's score) was recorded in all rabbits before euthanasia (N total = 65). In each group, 2 rabbits were used for iron concentration measurement (N total = 10), 2 rabbits were used for brain water content measurement (N total = 10), 3 rabbits were used for BBB permeability measurement (N total = 15), 3 rabbits were used for claudin-5, ZO-1 expression detection by Western Blotting (N total = 15), and 3 rabbits were used for claudin-5, ZO-1 mRNA detection by real-time PCR (N total = 15). On day 7, the rabbits were sacrificed and the perihematomal brain tissue was harvested to test the iron concentration, brain water content (BWC), tight junction proteins (claudin-5 and ZO-1) expression, and BBB permeability.Results: Purdy's score, iron concentration, and BWC were lower in the MIS and MIS + DFX groups compared to the HM and DFX groups. The MIS + DFX group showed a significant decrease in these indicators. The use of MIS to evacuate the hematoma led to increased expression levels of claudin-5 and ZO-1, as well as decreased BBB permeability. The MIS + DFX group exhibited a remarkable increase in claudin-5 and ZO-1 expression levels and a significant decrease in BBB permeability.Conclusions: MIS combined with DFX treatment could increase the expression levels of perihematomal tight junction proteins (claudin-5 and ZO-1) expression, reduce BBB permeability, and improve the neurological function. MIS combined with DFX treatment may also prevent secondary brain damage following ICH.
研究领域:
神经科学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oncotarget
·
2017
·
IF 5.168
Jianfa Wu,Lingjie Bao,Zhenbo Zhang,Xiaofang Yi
Induction of Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) has been demonstrated to be involved in cisplatin resistance in ovarian cancer. Solute carrier family 40 member 1 (SLC40A1) is an iron exporter, which possesses many putative Nrf2 binding sites. Here we hypothesize that it may be a possible downstream gene of Nrf2. Elevated level of Nrf2 and reduced level of SLC40A1 were found in cisplatin–resistant ovarian cancer cells as compared with cisplatin-sensitive ovarian cancer cells. Exogenous knockdown of Nrf2 leaded to increased expression of SLC40A1. While overexpression of Nrf2 resulted in decreased expression of SLC40A1. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay revealed that Nrf2 inhibited the transcription of SLC40A1. Overexpression of SLC40A1 was able to reverse cisplatin resistance induced by Nrf2, while knockdown of SLC40A1 restored cisplatin resistance and increased iron concentration. Desferal, an iron chelator, was found to overcome cisplatin resistance through iron deprivation. Its function was boosted when combined with brusatol, an Nrf2 inhibitor. Taken together, this study first demonstrated that Nrf2 could transcriptionally suppress the expression of SLC40A1. Iron overload induced by SLC40A1 resulted in cisplatin resistance in ovarian cancer. Targeting iron metabolism may be a new therapeutic strategy to reverse drug resistance in ovarian cancer treatment.
研究领域:
肿瘤学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Chao Hua,Fengbo Yang,Xiaoli Jia,Yichi Lu,Xiaoxiao Li,Peng Zhao,Malcolm Xing,Guozhong Lyu
Infection and vascular dysfunction are two major reasons for delayed wound healing, especially in the scenario of multidrug-resistant bacterial has been a challenge for antibiotics usage. Probiotics are effective in fighting pathogens, while avoiding the destruction of skin microbiome. However, the viability of probiotics is a major obstacle in clinical application. As a non-protein proangiogenic drug, deferoxamine (DFO) has significant advantages over traditional growth factors in terms of cost, storage and transportation conditions, and stability. However, there is still a problem of short half-life that requires reliable drug delivery carriers to maximize its effect. Here, we developed multiple-chambered microgels using electrospray and microfluidics. Lactobacillus fermentum (LF) and DFO, respectively, for the management of multidrug-resistant Pseudomonas aeruginosa (MPA) and promotion of wound healing. We first tested five probiotics isolated from healthy people and found LF inhibiting the growth of MPA by lowering local pH and antimicrobial substances. The multi-chambered microgels effectively inhibited MPA by delivering probiotics, they can also protect probiotics from antibiotics. DFO promoted the angiogenesis of human umbilical venous endothelial cells. The microgel system had good biocompatibility and hemocompatibility. In a MPA infected wound, the microgel system effectively alleviated wound infection by 87.44%, improved angiogenesis by 29.32% and accelerated wound healing. This work suggests that multi-compartmented microgels loaded with probiotics and deferoxamine have great potential in wounds with multidrug-resistant bacteria.
研究领域:
生物医学工程
·
微生物学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
Gels
·
2022
·Vol. 8
·期 8
·476
·
IF 4.432
Chengju Sheng,Xuemei Tan,Qing Huang,Kewen Li,Chao Zhou,Mingming Guo
Wounds, particularly under low-hydration conditions, require more time to repair successfully. Therefore, there is an urgent need to develop wound dressings that can accelerate wound healing. Hydrogels, which can maintain a moist environment around the wound and allow gas to pass through the material, act as antibacterial hydrogels as dressings and have great application value in the treatment of wounds. In addition, wound dressings (hydrogels) containing antibacterial capacity have lasting antibacterial effects and reduce damage to cells. In this work, we firstly synthesized two antibacterial agents: imidazolium poly(ionic liquids) containing sulfhydryl (Imidazole-SH) and ε-Poly(lysine) containing SH (EPL-SH). Then, lysine as a cross-linking agent, by “thiol-ene” click reaction, was mixed with Deferoxamine (DFO) to prepare the antibacterial hydrogels. The in vitro assays showed that the hydrogels could effectively killEscherichia coli(E. coli) andStaphylococcus aureus(S. aureus). In addition, it also could reduce the inflammatory response produced by Lipopolysaccharide (LPS). More importantly, according to the transwell and angiogenesis assays, DFO-incorporated hydrogels promoted the migration and vascular repair of human umbilical vein endothelial cells (HUVECs). All the results revealed that the hydrogels provided new strategies for wound dressings.Keywords:antibacterial hydrogels;imidazolium poly(ionic liquids);vascular repair;anti-inflammatory;deferoxamine
研究领域:
材料科学
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2023
·
IF 6.2
Xiaowen Xu,Hui Lin,Bixia Lin,Lingyi Huang,Pingping Wu,Youjia Wu,Liying Huang
Deferasirox (DEF) is essential for patients with thalassemia requiring long-term transfusion therapy. Tigecycline (TIGE) is a first-line drug for the clinical treatment of complex, severe bacterial infections. The two drugs can be coordinated to treat Pseudomonas aeruginosa infections. Easy and efficient techniques for monitoring these two drugs in biological samples are few. Metal–organic framework (Zn-MOF) prepared from zinc nitrate hexahydrate and dithioglycolic acid has a flower structure. Interestingly, Zn-MOF can cause DEF to aggregate on it and induce DEF luminescence. The principle may be that Zn-MOF limits the vibration and rotation of DEF to avoid its nonradiative jump, which triggers aggregation-induced emission (AIE) and exhibits intense fluorescence. Further investigation revealed that TIGE could decompose Zn-MOF, thus alleviating the inhibitory effect of Zn-MOF on DEF and reducing the fluorescence intensity of DEF@Zn-MOF. A DEF/TIGE detection biosensor was created based on the fluorescence "turn-on" effect of Zn-MOF on DEF and the fluorescence "turn-off" effect of TIGE on DEF@Zn-MOF. The proposed technique was subsequently used to identify DEF/TIGE levels in pharmaceuticals and human plasma. The mean values for the percentage of the labeled amount of DEF/TIGE in DEF dispersible tablets/TIGE injection were 104.5 and 104.9%, respectively. The detection limits for the fluorescence detection of DEF and TIGE were 3.6 and 1.2 nM, respectively. This fluorescence assay is the first application of MOF to the simultaneous detection of DEF and TIGE and has the advantages of rapid sensitivity and high selectivity , providing a new strategy for drug detection.
研究领域:
分析化学
·
药物检测
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2016
·
IF 4.219
Meng Tian,Xi Chen,Zhipeng Gu,Hao Li,Lu Ma,Xin Qi,Hong Tan,Chao You
Deferoxamine is commonly used for iron-overload related diseases, its drawbacks such as instability and toxicity, however, significantly limited its utility in clinic. To address these issues, oxidation-responsive alginate-deferoxamine (Alg-DFO) conjugates were synthesized and their structure was characterized. The metabolism studies shown the conjugation of alginate significantly increased the stability of the DFO, with half-life more than 10 times longer than that of the free DFO. Moreover, the conjugates could not only quickly respond to oxidative stimuli and degradation, suggesting their potential to be cleared from the body by responding to iron-overload associated oxidative environment to avoid its accumulation and safety concern, but also protect iron binding capacity of the attached DFO from oxidation. The degradation mechanism for oxidative-response was proposed. In addition, the conjugates shown lower cytotoxicity compared to the free DFO. Taken together, the Alg-DFO conjugates synthesized in this work has promise for treating iron-overload related conditions.
研究领域:
药学
·
生物化学
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）