Preparation and Evaluation of Recombinant Human Erythropoietin Loaded Tween 80-Albumin Nanoparticle for Traumatic Brain Injury Treatment

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2020 Nov 6

PMID 33154639

Citations 4

Authors

Yuanfeng Xue

Junhong Ding

Yulong Liu

Yuchun Pan

Penglai Zhao

Zhiwen Ren

Jian Xu

Liangliang Ye

Ying Xu

Affiliations

Soon will be listed here.

Abstract

Objective: Traumatic brain injury (TBI) is a serious health problem with few available treatment options. Rh-erythropoietin (rh-EPO) is a potential therapeutic drug for TBI, but it cannot cross the blood-brain barrier (BBB) directly. In this regard, a novel strategy to deliver rh-EPO for enhanced TBI treatment is via the development of Tween 80 modified albumin nanoparticles using electrostatic spray technology.

Methods: The rh-EPO loaded Tween 80 modified albumin nanoparticles (rh-EPO-Tw-ABNPs) were prepared by electrostatic spray technology, while the process parameters were optimized via a single factor design. Investigation of physicochemical properties, bioactivity and stability of rh-EPO-Tw-ABNPs was carried out. The in vitro release and biocompatibility with nerve cells were also analyzed. The in vivo brain targeting efficiency, brain edema relieving effect and the expression of aquaporin 4 (AQP4) and glial fibrillary acidic protein (GFAP) in the brain were evaluated in TBI model rats.

Results: The particle size of optimal rh-EPO-Tw-ABNPs was about 438 ± 45 nm, with a zeta potential of -25.42 ± 0.8 mv. The average drug loading ratio of rh-EPO-Tw-ABNPs was 21.3± 3.7 IU/mg with a relative bioactivity of 91.6 ± 4.1%. The in vitro release of rh-EPO from the nanoparticles was rather slow, while neither the blank Tw-ABNPs nor rh-EPO-Tw-ABNPs exhibited toxicity on the microglia cells. Furthermore, in vivo experiments indicated that the rh-EPO-Tw-ABNPs could enhance the distribution of EPO in the brain and relieve brain edema more effectively. Moreover, compared with an rh-EPO injection, the rh-EPO-Tw-ABNPs could increase the AQP4 level but reduced GFAP expression in the brain with more efficiency.

Conclusion: The rh-EPO-Tw-ABNPs could enhance the transport of rh-EPO into the brain with superior therapeutic effect for TBI.

Citing Articles

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References

Zoltewicz J, Scharf D, Yang B, Chawla A, Newsom K, Fang L . Characterization of Antibodies that Detect Human GFAP after Traumatic Brain Injury. Biomark Insights. 2012; 7:71-9. PMC: 3394595. DOI: 10.4137/BMI.S9873. View

Jang S, Park S, Kwon H . Relation between injury of the periaqueductal gray and central pain in patients with mild traumatic brain injury: Observational study. Medicine (Baltimore). 2016; 95(26):e4017. PMC: 4937934. DOI: 10.1097/MD.0000000000004017. View

Kwon E, Skalak M, Lo Bu R, Bhatia S . Neuron-Targeted Nanoparticle for siRNA Delivery to Traumatic Brain Injuries. ACS Nano. 2016; 10(8):7926-33. PMC: 5896006. DOI: 10.1021/acsnano.6b03858. View

Zhang B, Wang B, Cao S, Wang Y . Epigallocatechin-3-Gallate (EGCG) Attenuates Traumatic Brain Injury by Inhibition of Edema Formation and Oxidative Stress. Korean J Physiol Pharmacol. 2015; 19(6):491-7. PMC: 4637351. DOI: 10.4196/kjpp.2015.19.6.491. View

Juul S . Neuroprotective role of erythropoietin in neonates. J Matern Fetal Neonatal Med. 2012; 25 Suppl 4:105-7. DOI: 10.3109/14767058.2012.715025. View

Albert-Weissenberger C, Siren A . Experimental traumatic brain injury. Exp Transl Stroke Med. 2010; 2(1):16. PMC: 2930598. DOI: 10.1186/2040-7378-2-16. View

Verdonck O, Lahrech H, Francony G, Carle O, Farion R, van de Looij Y . Erythropoietin protects from post-traumatic edema in the rat brain. J Cereb Blood Flow Metab. 2007; 27(7):1369-76. DOI: 10.1038/sj.jcbfm.9600443. View

Liu H, Du K, Li D, Du Y, Xi J, Xu Y . A high bioavailability and sustained-release nano-delivery system for nintedanib based on electrospray technology. Int J Nanomedicine. 2018; 13:8379-8393. PMC: 6294062. DOI: 10.2147/IJN.S181002. View

Xiong Y, Mahmood A, Chopp M . Animal models of traumatic brain injury. Nat Rev Neurosci. 2013; 14(2):128-42. PMC: 3951995. DOI: 10.1038/nrn3407. View

10.

Carson K, Evens A, Bennett C, Luminari S . Clinical characteristics of erythropoietin-associated pure red cell aplasia. Best Pract Res Clin Haematol. 2005; 18(3):467-72. DOI: 10.1016/j.beha.2005.01.015. View

11.

Varshosaz J, Minaiyan M, Dayyani L . Poly(methyl vinyl ether-co-maleic acid) for enhancement of solubility, oral bioavailability and anti-osteoporotic effects of raloxifene hydrochloride. Eur J Pharm Sci. 2017; 112:195-206. DOI: 10.1016/j.ejps.2017.11.026. View

12.

Mehta P, Haj-Ahmad R, Rasekh M, Arshad M, Smith A, van der Merwe S . Pharmaceutical and biomaterial engineering via electrohydrodynamic atomization technologies. Drug Discov Today. 2016; 22(1):157-165. DOI: 10.1016/j.drudis.2016.09.021. View

13.

Gwak Y, Kang J, Unabia G, Hulsebosch C . Spatial and temporal activation of spinal glial cells: role of gliopathy in central neuropathic pain following spinal cord injury in rats. Exp Neurol. 2011; 234(2):362-72. PMC: 3303938. DOI: 10.1016/j.expneurol.2011.10.010. View

14.

Barzo P, Marmarou A, Fatouros P, Hayasaki K, Corwin F . Contribution of vasogenic and cellular edema to traumatic brain swelling measured by diffusion-weighted imaging. J Neurosurg. 1997; 87(6):900-7. DOI: 10.3171/jns.1997.87.6.0900. View

15.

Si D, Wang H, Wang Q, Zhang C, Sun J, Wang Z . Progesterone treatment improves cognitive outcome following experimental traumatic brain injury in rats. Neurosci Lett. 2013; 553:18-23. DOI: 10.1016/j.neulet.2013.07.052. View

16.

Lehmann G, Gradilone S, Marinelli R . Aquaporin water channels in central nervous system. Curr Neurovasc Res. 2005; 1(4):293-303. DOI: 10.2174/1567202043362081. View

17.

Arya N, Chakraborty S, Dube N, Katti D . Electrospraying: a facile technique for synthesis of chitosan-based micro/nanospheres for drug delivery applications. J Biomed Mater Res B Appl Biomater. 2008; 88(1):17-31. DOI: 10.1002/jbm.b.31085. View

18.

Alyautdin R, Petrov V, Langer K, Berthold A, Kharkevich D, Kreuter J . Delivery of loperamide across the blood-brain barrier with polysorbate 80-coated polybutylcyanoacrylate nanoparticles. Pharm Res. 1997; 14(3):325-8. DOI: 10.1023/a:1012098005098. View

19.

Alyautdin R, Tezikov E, Ramge P, Kharkevich D, Begley D, Kreuter J . Significant entry of tubocurarine into the brain of rats by adsorption to polysorbate 80-coated polybutylcyanoacrylate nanoparticles: an in situ brain perfusion study. J Microencapsul. 1998; 15(1):67-74. DOI: 10.3109/02652049809006836. View

20.

Yacoby I, Bar H, Benhar I . Targeted drug-carrying bacteriophages as antibacterial nanomedicines. Antimicrob Agents Chemother. 2007; 51(6):2156-63. PMC: 1891362. DOI: 10.1128/AAC.00163-07. View