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An injectable bioactive dressing based on platelet-rich plasma and nanoclay:Sustained release of deferoxamine to accelerate chronic wound healing

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Acta Pharmaceutica Sinica B 2023年第10期13卷 4318-4336页

作者： Jiao Zhang Qian Luo Qian Hu Tiantian Zhang Jingyu Shi Li Kong Dehao Fu Conglian Yang Zhiping Zhang Tongji School of Pharmacy Huazhong University of Science and TechnologyWuhan 430030China Liyuan Hospital of Tongji Medical College of Huazhong University of Science and Technology Wuhan 430030China Department of Orthopaedics Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China National Engineering Research Center for Nanomedicine Huazhong University of Science and TechnologyWuhan 430030China Hubei Engineering Research Center for Novel Drug Delivery System Huazhong University of Science and TechnologyWuhan 430030China

Delayed diabetic wound healing has placed an enormous burden on society.The key factors limiting wound healing include unresolved inflammation and impaired angiogenesis.Platelet-rich plasma(PRP)gel,a popular biomaterial in the field of regeneration,has limited applications due to its non-injectable properties and rapid release and degradation of growth factors.Here,we prepared an injectable hydrogel(DPLG)based on PRP and laponite by a simple one-step mixing method.Taking advantages of the non-covalent interactions,DPLG could overcome the limitations of PRP gels,which is injectable to fill irregular injures and could serve as a local drug reservoir to achieve the sustained release of growth factors in PRP and deferoxamine(an angiogenesis promoter).DPLG has an excellent ability in accelerating wound healing by promoting macrophage polarization and angiogenesis in a full-thickness skin defect model in typeⅠdiabetic rats and normal rats.Taken together,this study may provide the ingenious and simple bioactive wound dressing with a superior ability to promote wound healing.

关键词： Injectable hydrogels Diabetic wound healing Platelet-rich plasma Laponite deferoxamine Angiogenesis Macrophage polarization

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Carrier-Free deferoxamine Nanoparticles against Iron Overload in Brain

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CCS Chemistry 2023年第1期5卷 257-270页

作者： Fang Zhu Jian Zhong Junfei Hu Peng Yang Jianhua Zhang Minghua Zhang Yiwen Li Zhipeng Gu College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengduSichuan 610065 State Key Laboratory of Biotherapy and Cancer West China HospitalSichuan University and Collaborative Innovation CenterChengdu 610041

Although considerable progress has been achieved in treating iron-overload diseases with deferoxamine(DFO)-based biomaterials,high DFO loading and multifunctional integration in one system are still grand challenges.Herein,a series of carrier-free,high DFO-loading(∼80%),uniform spherical nanoparticles(NPs)assisted by polyphenols have been facilely developed with both efficient iron and reactive oxygen species-scavenging properties.Interestingly,those DFO-based NPs have demonstrated excellent scavenging performance in iron-overloaded cell model and energetically exhibited brain cell protection in vivo in intracerebral hemorrhage animal models.This study could provide a promising strategy to significantly improve the curative effect of DFO delivery systems for iron-overload diseases.

关键词： carrier-free deferoxamine nanoparticles iron scavenging reactive oxygen species scavenging

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deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis

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Neural Regeneration Research 2019年第3期14卷 532-541页

作者： Xue Yao Yan Zhang Jian Hao Hui-Quan Duan Chen-Xi Zhao Chao Sun Bo Li Bao-You Fan Xu Wang Wen-Xiang Li Xuan-Hao Fu Yong Hu Chang Liu Xiao-Hong Kong Shi-Qing Feng Department of Orthopedics Tianjin Medical University General Hospital State Key Laboratory of Medicinal Chemical Biology Nankai University International Science and Technology Cooperation Base of Spinal Cord Injury Department of Orthopedics Nankai Hospital Department of Orthopedic and Traumatology The University of Hong Kong Pokfulam Hong Kong Special Administrative Region School of Medicine Nankai University Tianjin Neurological Institute Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System Ministry of Education and Tianjin City

Ferroptosis is an iron-dependent novel cell death pathway. deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition represents the mechanism of action of deferoxamine on spinal cord injury recovery. A rat model of deferoxamine at thoracic 10 segment was established using a modified Allen's method. Ninety 8-week-old female Wistar rats were used. Rats in the deferoxamine group were intraperitoneally injected with 100 mg/kg deferoxamine 30 minutes before injury. Simultaneously, the Sham and deferoxamine groups served as controls. Drug administration was conducted for 7 consecutive days. The results were as follows:(1) Electron microscopy revealed shrunken mitochondria in the spinal cord injury group.(2) The Basso, Beattie and Bresnahan locomotor rating score showed that recovery of the hindlimb was remarkably better in the deferoxamine group than in the spinal cord injury group.(3) The iron concentration was lower in the deferoxamine group than in the spinal cord injury group after injury.(4) Western blot assay revealed that, compared with the spinal cord injury group, GPX4, xCT, and glutathione expression was markedly increased in the deferoxamine group.(5) Real-time polymerase chain reaction revealed that, compared with the deferoxamine group, mRNA levels of ferroptosis-related genes Acyl-CoA synthetase family member 2(ACSF2) and iron-responsive element-binding protein 2(IREB2) were up-regulated in the deferoxamine group.(6) deferoxamine increased survival of neurons and inhibited gliosis. These findings confirm that deferoxamine can repair spinal cord injury by inhibiting ferroptosis. Targeting ferroptosis is therefore a promising therapeutic approach for spinal cord injury.

关键词： nerve regeneration iron spinal cord injury secondary injury ferroptosis deferoxamine GPX4 xCT treatment astrogliosis lipid peroxidation neural regeneration

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deferoxamine improves neurological function in a rat model of experimental spinal cord injury

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Neural Regeneration Research 2011年第35期6卷 2751-2755页

作者： Yanting Wang Shaoji Yuan Fachen Wang Rong HU Jiangkai Lin Zisheng Liu Hua Feng Department of Neurosurgery Southwest Hospital Third Military Medical University Chongqing 400038 China Department of Neurosurgery General Hospital of Jinan Military Area Command Jinan 250031 Shandong Province China

A rat model of spinal cord injury was established using modified Allen＇s method and treated with the ferric iron-chelating agent, deferoxamine. Hematoxylin-eosin, Nissl and Perl＇s Prussian blue staining, at 7 14 days following spinal cord injury, showed that following deferoxamine treatment, glial cells proliferation increased significantly, nerve cell morphology was improved and hemosiderin was significantly reduced in the injury region. At 1 56 days following injury, Basso, Beattie, and Bresnahan Locomotor Rating Scale scores were increased, while latencies of somatosensory-evoked potentials and motor-evoked potentials were decreased. Results demonstrate that deferoxamine can promote neurological functional recovery after experimental spinal cord injury in rats.

关键词： spinal cord injury ferric iron deferoxamine neurological function neural regeneration

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Neuroprotective effect of deferoxamine on erastin-induced ferroptosis in primary cortical neurons

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Neural Regeneration Research 2020年第8期15卷 1539-1545页

作者： Yan Zhang Bao-You Fan Yi-Lin Pang Wen-Yuan Shen Xu Wang Chen-Xi Zhao Wen-Xiang Li Chang Liu Xiao-Hong Kong Guang-Zhi Ning Shi-Qing Feng Xue Yao Department of Orthopedics General Hospital of Tianjin Medical UniversityTianjinChina International Science and Technology Cooperation Base of Spinal Cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryTianjinChina Laboratory of Medical Molecular Virology School of MedicineNankai UniversityTianjinChina

The iron chelator deferoxamine has been shown to inhibit ferroptosis in spinal cord injury.However,it is unclear whether deferoxamine directly protects neurons from ferroptotic cell death.By comparing the survival rate and morphology of primary neurons and SH-SY5Y cells exposed to erastin,it was found that these cell types respond differentially to the duration and concentration of erastin treatment.Therefore,we studied the mechanisms of ferroptosis using primary cortical neurons from E16 mouse embryos.After treatment with 50μM erastin for 48 hours,reactive oxygen species levels increased,and the expression of the cystine/glutamate antiporter system light chain and glutathione peroxidase 4 decreased.Pretreatment with deferoxamine for 12 hours inhibited these changes,reduced cell death,and ameliorated cellular morphology.Pretreatment with the apoptosis inhibitor Z-DEVD-FMK or the necroptosis inhibitor necrostain-1 for 12 hours did not protect against erastin-induced ferroptosis.Only deferoxamine protected the primary cortical neurons from ferroptosis induced by erastin,confirming the specificity of the in vitro ferroptosis model.This study was approved by the Animal Ethics Committee at the Institute of Radiation Medicine of the Chinese Academy of Medical Sciences,China(approval No.DWLL-20180913)on September 13,2018.

关键词： cystine/glutamate antiporter system light chain deferoxamine erastin ferroptosis glutathione peroxidase 4 neurons neuroprotection reactive oxygen species

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Baicalin and deferoxamine alleviate iron accumulation in different brain regions of Parkinson's disease rats

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Neural Regeneration Research 2012年第27期7卷 2092-2098页

作者： Pei Xiong Xin Chen Chunyan Guo Nan Zhang Baocang Ma Department of Chinese Materia Medica Pharmacology Traditional Chinese Medicine School Capital Medical University Beijing 100069China

Previous studies found that iron accumulates in the substantia nigra of Parkinson＇s disease patients However, it is still unclear whether other brain regions have iron accumulation as well. In this experiment, rats with rotenone-induced Parkinson＇s disease were treated by gastric perfusion of baicalin or intraperitoneal injection of deferoxamine. Immunohistochemical staining demonstrated that iron accumulated not only in the substantia nigra pars compacta, but also significantly in the striatum globus pallidus, the dentate gyrus granular layer of the hippocampus, the dentate-interpositus and the facial nucleus of the cerebellum. Both baicalin and deferoxamine, which are iron chelating agents, significantly inhibited iron deposition in these brain areas, and substantially reduced the loss of tyrosine hydroxylase-positive cells. These chelators also reduced iron content in the substantia nigra. In addition to the substantia nigra, iron deposition was observed in other brain regions as well. Both baicalin and deferoxamine significantly inhibited iron accumulation in different brain regions, and had a protective effect on dopaminergic neurons.

关键词： Parkinson＇s disease rotenone iron baicalin deferoxamine substantia nigra striatum hippocampus cerebellum neurodegenerative disease regeneration neural regeneration

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The Effect of Hemin and deferoxamine on Selenium, Zinc, and Iron Levels of K562 Cells

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Journal of Cancer Therapy 2011年第1期2卷 65-70页

作者： Bahire Kucukkaya Lale Afrasyap Department of Biophysics Faculty of MedicineMaltepe UniversityIstanbulTURKEY Mugla School of Health Sciences Mugla UniversityMuglaTURKEY

This study investigated contents of trace elements selenium, zinc and iron both in control K562 cells, human leukemia cell line, and cells treated with hemin or the iron chelator deferoxamine cells. K562 cell line was grown in RPMI medium supplemented with 10% fetal calf serum, 100 IU/mL penicillin, 100 μg/mL streptomycin, 25 μg/mL amphotericin B and 2 mM L-glutamine at 37?C in humidified air containing 5% CO2. K562 cells were treated with hemin and deferoxamine from the first day to the fifth day. The trace element levels were measured by inductively coupled plasma optical emission spectrometry. Treatment of K562 cells with hemin resulted in an increase in the levels of selenium on fifth day compared with first day. No differences were observed in selenium levels of the control group compared with the hemin-induced group. Also there were no significant differences observed in the zinc levels of control cells compared with deferoxamine- and hemin-induced cells. Iron levels of hemin-induced cells were decreased on the fourth day com-pared with the third day. On the third day, iron levels of hemin-induced cells were significantly increased compared to the control group. Our observations suggest that alterations of selenium and zinc levels may play a role in hemin-induction and deferoxamine-inhibition, respectively. On the other hand, iron levels may influence both in hemin-induction and deferoxamine-inhibition of K562 human leukemia cell

关键词： Hemin deferoxamine DFO K562 Selenium Zinc Iron Trace Elements

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Neutrophilia-Inducing deferoxamine in Mice Infected with <i>Staphylococcus aureus</i>

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Open Journal of Pathology 2013年第2期3卷 99-106页

作者： Mohemid M. Al-Jebouri Nihad A. Jafar Department of Microbiology College of Medicine University of Tikrit Tikrit Iraq

The ability to sequester iron is a primary defense mechanism against bacterial infection. Iron chelation therapy has been considered as a possible treatment for various infectious diseases. S. aureus isolated from neonatal septicemia were used to study the effect of deferoxamine and sub-minimal inhibitory concentration of gentamicine on some virulence factors of this isolates. Also an experimental sepsis was inducted in mice and treated with gentamicin and deferoxamine. The expression of virulence factor (alpha-hemolysin, beta-hemolysin, delta-hemolysin, coagulase, and DNase) by Staphylococcus?aureus isolates was significantly decreased (p deferoxamine treatment had an additional effect on survival and bacterial eradication from the organs of septicemic mice. In vitro exposure of S. aureus isolated to gentamicin and deferoxamine led to a decrease in the production of some virulence factors by these isolates.

关键词： Neutrophilia deferoxamine Gentamicin S. aureus Pathology

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Therapeutic Drug Monitoring of Chelating Agent deferoxamine for <i>β</i>-Thalassemia Major Patients

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International Journal of Clinical Medicine 2013年第8期4卷 331-342页

作者： Rawa Ratha Tagreed Altaei Department of Clinical Pharmacy College of Pharmacy Sulaimany University Sulaimany Iraq Department of Pharmacology and Toxicology College of Pharmacy Hawler Medical University Erbil Iraq

Therapeutic drug monitoring is used to prevent or decrease the risk associated with the toxic effects of medication. This study aims to evaluate the potential advantages of Therapeutic Drug Monitoring (TDM) of subcutaneous deferoxamine injection and prevention of clinical problems in β-thalassaemia major patients. Patients & Methods: Fifty-four thalassemia patients were allocated into two groups;missing, and not missing deferoxamine dose. TDM of deferoxamine injection and it clinical outcomes was critically studied under the following subheadings: assessment of the adequacy of deferoxamine usage, serum peak and trough concentrations of deferoxamine and ferroxamine with needed pharmacokinetics, cardiac parameters and biomarkers, biochemical and hematological indices, adverse effects/toxicity, urinary assessment of Fe, Zn, selenium, and copper levels, compliance to treatment, dose adjustment in correlation to therapeutic index and life style. Results: Demographic data showed no significant difference. Peak plasma concentrations were 144.83±69 and 43.54±39.16 μg/L, while trough concentrations were 33±26.32 and 31.13±21.58 μg/L of deferoxamine and ferroxamine, respectively. The elimination rate constant was 0.0237±0.00029 min-1, half-life was 34 min, and distribution volume was 0.93±0.078. Although cardiac parameters showed no significant differences, there were significant differences in CK-MB, and hsCRP levels;troponin I value could not be detected. Biochemical and hematological studies showed significant differences in Ferritin B, urea, SGPT, SGOT, alkaline phosphatase, serum albumin and serum calcium. Assessment of adverse effects/toxicity showed significant differences. The correlation of serum ferritin to therapeutic index, and the life style including Vitamin C and/or E administration were assessed for the compliance to treatment. Conclusion: Therapeutic monitoring of chelation therapy by deferoxamine in β-thalassemia patients is necessary to ensure effective treatment, compliance, and to avoid adverse side ef

关键词： Therapeutic Drug Monitoring deferoxamine β-Thalassemia Major

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Baicalin suppresses iron accumulation after substantia nigra injury: relationship between iron concentration and transferrin expression

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Neural Regeneration Research 2014年第6期9卷 630-636页

作者： Chunyan Guo Xin Chen Pei Xiong Traditional Chinese Medicine School Capital Medical University

Previous studies have shown that baicalin prevented iron accumulation after substantia nigra injury, reduced divalent metal transporter 1 expression, and increased ferroportin 1 expression in the substantia nigra of rotenone-induced Parkinson＇s disease rats. In the current study, we investigated the relationship between iron accumulation and transferrin expression in C6 cells, to explore the mechanisms of the inhibitory effect of baicalin on iron accumulation observed in Parkinson＇s disease rats. Iron content was detected using inductively coupled plasma-atomic emission spectroscopy. Results showed that iron content decreased 41% after blocking divalent metal transporter 1 and ferroportin 1 proteins. After treatment with ferric ammonium citrate of differing concentrations （10, 50, 100, 400 ktg/mL） in C6 glioma cells, cell survival rate and ferroportin 1 expression were negatively correlated with ferric ammonium citrate concentration, but divalent metal transporter 1 expression positively correlated with ferric ammonium citrate concentration. Baicalin or deferoxamine reduced divalent metal transporter 1 expression, but increased ferroportin 1 expression in the 100 μg/mL ferric ammonium citrate-loaded C6 cells. These results indicate that baicalin down-regulated iron concentration, which positively regulat- ed divalent metal transporter 1 expression and negatively regulated ferroportin 1 expression, and decreased iron accumulation in the substantia nigra.

关键词： nerve regeneration Parkinson＇s disease iron baicalin divalent metal transporter 1 ferroportin 1 deferoxamine C6 cells the Scientific Research Common Program of Beijing MunicipalCommission of Education neural regeneration

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