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Erythropoietin Nanopariticles: Therapy for Cerebral Ischemic Injury and Metabolize in Kidney

Ting Wang1,aYan Hu2Long Zhang2Li Jiang2Nongyue He1()
State key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China
Teaching and Research Section of Pediatrics, Clinical Medical College, Southeast University, Nanjing 210009, China

a Present address: 930 N. University Ave, room 4624, Ann Arbor, MI, USA. 48109, E-mail: wangting@umich.edu

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Abstract

Ischemic metabolism in the enterogram is a crucial issue of clinical concern for deep understanding of drug delivery. In this study we use nanochemistry in micelle to produce the nanocarrier of erythropoietin (EPO) and traced the metabolizable process of the EPO carrier in vivo. Nascence Sprague-Dawley rats of 5 days are treated with EPO-loading nanocarriers. Curative effects of the EPO nanocarriers for periventricular leukomalacia (PVL) models are validated by the analysis of pathology and praxiology of the mice. We demonstrate in vivo that EPO nanocarriers can ameliorate drug-induced liquefaction caused by hypoxia. By tracking the metabolism of EPO in liver and kidney, we suggest that nanocarriers effectively prolong the metabolic half-life and clearance time of EPO. HPLC results show that exciting amino acid toxicity was inhibited, since mobilization of late oligodendrocyte can be protected by treatment of EPO vehicles from hypoxia.

References

[1]

Kumral A, Gonenc S, Acikgoz O, Sonmez A, Genc K, Yilmaz O, Gokmen N, Duman N, Ozkan H. Erythropoietin increases glutathione peroxidase enzyme activity and decreases lipid peroxidation levels in hypoxic-ischemic brain injury in neonatal rats. Biol Neonate 2005; 87: 15-18. doi: 10.1159/000080490

[2]

Kumral A, Ozer E, Yilmaz O, Akhisaroglu M, Gokmen N, Duman N, Ulukus C, Genc S, Ozkan H. Erythropoietin protects against necrotizing enterocolitis of newborn rats by the inhibiting nitric oxide formation. Biol Neonate 2003; 83: 224-228. doi: 10.1159/000068926

[3]

Kumral A, Uysal N, Tugyan K, Sonmez A, Yilmaz O, Gokmen N, Kiray M, Genc S, Duman N, Koroglu TF, Ozkan H, Genc K. Erythropoietin improves long-term spatial memory deficits and brain injury following neonatal hypoxia-ischemia in rats. Behav Brain Res 2004; 153: 77-86. doi: 10.1016/j.bbr.2003.11.002

[4]

McClure MM, Threlkeld SW, Fitch RH. The effects of erythropoietin on auditory processing following neonatal hypoxic–ischemic injury. Brain Res. 2006; 1087: 190-195. doi: 10.1016/j.brainres.2006.03.016

[5]

Siren AL, Fratelli M, Brines M, Goemans C, Casagrande S, Lewczuk P, Keenan S, Gleiter C, Pasquali C, Capobianco A, Mennini T, Heumann R, Cerami A, Ehrenreich H, Ghezzi P. Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci USA 2001; 98: 4044-4049. doi: 10.1073/pnas.051606598

[6]

Calvillo L, Latini R, Kajstura J, Leri A, Anversa P, Ghezzi P, Salio M, Cerami A, Brines M. Recombinant human erythropoietin protects the myocardium from ischemiareperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci USA 2003; 100: 4802–4806. doi: 10.1073/pnas.0630444100

[7]

Parsa CJ, Matsumoto A, Kim J, Riel RU, Pascal LS, Walton GB, Thompson RB, Petrofski JA, Annex BH, Stamler JS, Koch WJ. A novel protective effect of erythropoietin in the infarcted heart. J Clin Invest 2003; 112: 999–1007. doi: 10.1172/JCI200318200

[8]

Bagul A, Hosgood SA, Kaushik M, et al. Effects of erythropoietin on ischaemia/reperfusion injury in a controlled nonheart beating donor kidney model. Transplant international, 2008; 21: 495-510. doi: 10.1111/j.1432-2277.2007.00636.x

[9]

Spandou E, Papadopoulou Z, Soubasi V, Karkavelas G, Simeonidou C, Pazaiti A, Guiba-Tziampiri O. Erythropoietin prevents long-term sensorimotor deficits and brain injury following neonatal hypoxia-ischemia in rats. Brain Res. 2005; 1045: 22-30.

[10]

Wei L, Han BH, Li Y, Keogh CL, Holtzman DM, Yu SP. Cell Death Mechanism and Protective Effect of Erythropoietin after Focal Ischemia in the Whisker-Barrel Cortex of Neonatal Rats. JPET 2006; 317: 109-116. doi: 10.1124/jpet.105.094391

[11]

Kellert BA, McPherson RJ, Juul SE. A comparison of highdose recombinant erythropoietin treatment regimens in brain-injured neonatal rats. Pediatric Res 2007; 61: 451-455. doi: 10.1203/pdr.0b013e3180332cec

[12]

Wang T, Zhang, L, Jiang L, Nongyue He. Neurotoxicological effects of 3-nitropropionic acid on the neonatal rat. NeuroToxicol. 2008; 29: 1023-1029. doi: 10.1016/j.neuro.2008.07.006

[13]

Yang WJ, Wang T, He NY. Preparation and Property of Chitosan/Sodium Tripolyphosphate Microcapsules as Drug Carrier. Chem J Chinese U. 2009; 30: 625-628.

[14]

Salazar, J., Campbell M, Anderson S, Gardner S, Dunnum J. New records of Bolivian mammals. Mammalia 1994; 1: 125-130. doi: 10.1515/mamm.1994.58.1.125

[15]

Tozaki H, Odoriba T, Okada N, Fujita T, Terabe A, Suzuki T, Okabe S, Muranishi S, Yamamoto A. Use of protease inhibitors to improve calcitonin absorption from the small and large intestine in rats. J Pharm Sci. 1997; 86: 1016–1021. doi: 10.1021/js970018g

[16]

Mahesh D. Chavanpatil, Ayman Khdair, Jayanth Panyam, Nanoparticles for Cellular Drug Delivery: Mechanisms and Factors Influencing Delivery. J. Nanosci. Nanotechnol 2006; 6: 2651–2663.

[17]

Kamat JP, Narurkar LM, Narurkar MV. Induction of hepatic drug-metabolizing enzymes by DL-methionine in rats. Journal of Biosciences 1989; 14: 233-241.

[18]

Esneault E, Pacary E, Eddi D, et al. Combined therapeutic strategy using erythropoietin and mesenchymal stem cells potentiates neurogenesis after transient focal cerebral ischemia in rats. J. Cerebral Blood Flow & Metabolism 2008; 28: 1552–1563. doi: 10.1007/BF02716683

[19]

Perlman JM. Ola DS. Summary proceedings from the neurology group on Hypoxic-ischemic encephalopathy. Pediatrics 2006; 117: S28-S33. doi: 10.1038/jcbfm.2008.40

[20]

Palmer C. Hypoxic-ischemic encephalopathy: Therapeutic approaches against microvascular injury, and role of neutrophils, PAF, and free radicals. Clinics in Perinatology 1995; 22: 481-517.

[21]

Bao CC, Yang H, Sheng P, Song H, Ding XH, Liu B, Lu YC, Hu GH, Cui DX. Cloning, Expression, Monoclonal Antibody Preparation of Human Gene NBEAL1 and Its Application in Targeted Imaging of Mouse Glioma. Nano Biomed Eng 2009; 1: 74-87.

[22]

Li H, Zhang YG, Huang WP. Photoactivation of Ionexchangeable Trititanate Nanotubes Modified by MS (M = Cd, Zn) Nanoparticles. Nano Biomed Eng 2009; 1: 48-56.

[23]

Cui DX, Han YD, Li ZM, Song H, Wang K, He R, Liu B, Liu HL, Bao CC, Huang P, Ruan J, Gao P, Yang H, Cho HS, Ren QS, Shi DL. Fluorescent Magnetic Nanoprobes for in vivo Targeted Imaging and Hyperthermia Therapy of Prostate Cancer. Nano Biomed Eng 2009; 1: 94-112.

[24]

Yang WJ, Wang T, Fu J, He NY, Chitosan/Sodium Tripolyphosphate Nanoparticles: Preparation, Characterization and Application as Drug Carrier. J Biomed Nanotechnol. 2009; 5: 591–595. doi:10.1166/jbn.2009.1067

Nano Biomedicine and Engineering
Pages 31-39
Cite this article:
Wang T, Hu Y, Zhang L, et al. Erythropoietin Nanopariticles: Therapy for Cerebral Ischemic Injury and Metabolize in Kidney. Nano Biomedicine and Engineering, 2010, 2(1): 31-39. https://doi.org/10.5101/nbe.v2i1.p31-39
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