Skip to main content
SpringerLink
Log in

Synthesis of Biocompatible Titanate Nanofibers for Effective Delivery of Neuroprotective Agents

  • Protocol
  • First Online:
Neurotrophic Factors

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1727))

Abstract

Nanoscience provides us with new opportunities to develop nanotechnologies for treating, in particular, central nervous system disorders such as Alzheimer disease and multiple sclerosis. From a methodological point of view, it is challenging to deliver drugs effectively across the blood-brain barrier and blood-cerebrospinal fluid barrier. Our 10-year data and reports from both in vivo and in vitro studies, however, have consistently proved that therapeutic drugs of different types can be generally loaded in/on the nanocarriers for targeted and programmable deliveries to the central nervous system with a high degree of efficacy. This chapter presents a protocol for the synthesis of biocompatible titanate nanofibers as low-cost drug delivery cargos. In addition, a procedure for loading the neuroprotective agent Cerebrolysin onto the nanofibers is briefly described. Finally, experimental observations on the use of nanodrug delivery for superior neuroprotective effects of Cerebrolysin in traumatic brain injury are given as a proof of concept as compared to normal drug alone.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Sharma HS, Ali S, Tian ZR, Patnaik R, Patnaik S, Lek P et al (2009) Nano-drug delivery and neuroprotection in spinal cord injury. J Nanosci Nanotechnol 9:5014–5037

    Article  CAS  PubMed  Google Scholar 

  2. Misra A, Ganesh S, Shahiwala A, Shah SP (2003) Drug delivery to the central nervous system: a review. J Pharm Pharm Sci 6:252–273

    CAS  PubMed  Google Scholar 

  3. Weiss N, Miller F, Cazaubon S, Couraud P-O (2009) The blood-brain barrier in brain homeostasis and neurological diseases. Biochim Biophys Acta Biomembr 1788:842–857

    Article  CAS  Google Scholar 

  4. Kim MS, El-Fiqi A, Kim J-W, Ahn H-S, Kim H, Son Y-J et al (2016) Nanotherapeutics of PTEN inhibitor with mesoporous silica nanocarrier effective for axonal outgrowth of adult neurons. ACS Appl Mater Interfaces 8:18741–18753

    Article  CAS  PubMed  Google Scholar 

  5. Sharma G, Modgil A, Zhong T, Sun C, Singh J (2014) Influence of short-chain cell-penetrating peptides on transport of doxorubicin encapsulating receptor-targeted liposomes across brain endothelial barrier. Pharm Res 31:1194–1209

    Article  CAS  PubMed  Google Scholar 

  6. Li AJ, Zheng YH, Liu GD, Liu WS, Cao PC, Bu ZF (2015) Efficient delivery of docetaxel for the treatment of brain tumors by cyclic RGD-tagged polymeric micelles. Mol Med Rep 11:3078–3086

    Article  CAS  PubMed  Google Scholar 

  7. Li C, Li S, Tu T, Qi X, Xiong Y, Du S et al (2015) Paclitaxel-loaded cholesterol-conjugated polyoxyethylene sorbitol oleate polymeric micelles for glioblastoma therapy across the blood-brain barrier. Polym Chem 6:2740–2751

    Article  CAS  Google Scholar 

  8. Wu W, Lee SY, Wu X, Tyler JY, Wang H, Ouyang Z et al (2014) Neuroprotective ferulic acid (FA)-glycol chitosan (GC) nanoparticles for functional restoration of traumatically injured spinal cord. Biomaterials 35:2355–2364

    Article  CAS  PubMed  Google Scholar 

  9. Zhu S-P, Wang Z-G, Zhao Y-Z, Wu J, Shi H-X, Ye L-B et al (2015) Gelatin nanostructured lipid carriers incorporating nerve growth factor inhibit endoplasmic reticulum stress-induced apoptosis and improve recovery in spinal cord injury. Mol Neurobiol 53:4375–4386

    Article  PubMed  Google Scholar 

  10. Ye D, Raghnaill MN, Bramini M, Mahon E, Åberg C, Salvati A et al (2013) Nanoparticle accumulation and transcytosis in brain endothelial cell layers. Nanoscale 5:11153–11165

    Article  CAS  PubMed  Google Scholar 

  11. Kumar P, Choonara YE, Modi G, Naidoo D, Pillay V (2014) Nanoparticulate strategies for the five R’s of traumatic spinal cord injury intervention: restriction, repair, regeneration, restoration and reorganization. Nanomedicine (Lond) 9:331–348

    Article  CAS  Google Scholar 

  12. Pathan SA, Iqbal Z, Talegaonkar S, Vohra D, Jain GK, Azeem A, Jain N, Lalani JR et al (2009) CNS drug delivery systems: novel approaches. Recent Patents Drug Deliv Formul 3:71–89

    Article  CAS  Google Scholar 

  13. Saraiva C, Praca C, Ferreira R, Santos T, Ferreira L, Bernardino L (2016) Nanoparticle-mediated brain drug delivery: overcoming blood-brain barrier to treat neurodegenerative diseases. J Control Release 235:34–47

    Article  CAS  PubMed  Google Scholar 

  14. Sharma HS, Sharma A, Mössler H, Muresanu DF (2012) Neuroprotective effects of cerebrolysin, a combination of different active fragments of neurotrophic factors and peptides on the whole body hyperthermia-induced neurotoxicity: modulatory roles of co-morbidity factors and nanoparticle intoxication. Int Rev Neurobiol 102:249–276

    Article  CAS  PubMed  Google Scholar 

  15. Sharma HS, Zimmermann-Meinzingen S, Johanson CE (2010) Cerebrolysin reduces blood-cerebrospinal fluid barrier permeability change, brain pathology, and functional deficits following traumatic brain injury in the rat. Ann N Y Acad Sci 1199:125–137

    Article  CAS  PubMed  Google Scholar 

  16. Menon PK, Muresanu DF, Sharma A, Mössler H, Sharma HS (2012) Cerebrolysin, a mixture of neurotrophic factors induces marked neuroprotection in spinal cord injury following intoxication of engineered nanoparticles from metals. CNS Neurol Disord Drug Targets 11:40–49

    Article  CAS  PubMed  Google Scholar 

  17. Sharma HS, Muresanu DF, Sharma A (2016) Alzheimer’s disease: cerebrolysin and nanotechnology as a therapeutic strategy. Neurodegener Dis Manag 6:453–456

    Article  PubMed  Google Scholar 

  18. Sharma HS, Menon PK, Lafuente JV, Aguilar ZP, Wang YA, Muresanu DF, Mössler H, Patnaik R, Sharma A (2014) The role of functionalized magnetic iron oxide nanoparticles in the central nervous system injury and repair: new potentials for neuroprotection with Cerebrolysin therapy. J Nanosci Nanotechnol 14:577–595

    Article  CAS  PubMed  Google Scholar 

  19. Sharma HS, Muresanu DF, Lafuente JV, Nozari A, Patnaik R, Skaper SD, Sharma A (2016) Pathophysiology of blood-brain barrier in brain injury in cold and hot environments: novel drug targets for neuroprotection. CNS Neurol Disord Drug Targets 15:1045–1071

    Article  CAS  PubMed  Google Scholar 

  20. Sharma HS, Wiklund L, Badgaiyan RD, Mohanty S, Alm P (2006) Intracerebral administration of neuronal nitric oxide synthase antiserum attenuates traumatic brain injury-induced blood-brain barrier permeability, brain edema formation, and sensory motor disturbances in the rat. Acta Neurochir Suppl 96:288–294

    Article  PubMed  Google Scholar 

  21. Sharma HS (2005) Methods to produce brain hyperthermia. Curr Protoc Toxicol Chapter 11:Unit11.14. https://doi.org/10.1002/0471140856.tx1114s23

    PubMed  Google Scholar 

  22. Sharma HS (2007) Methods to produce hyperthermia-induced brain dysfunction. Prog Brain Res 162:173–199

    Article  CAS  PubMed  Google Scholar 

  23. Sharma A, Menon P, Muresanu DF, Ozkizilcik A, Tian ZR, Lafuente JV, Sharma HS (2016) Nanowired drug delivery across the blood-brain barrier in central nervous system injury and repair. CNS Neurol Disord Drug Targets 15:1092–1117

    Article  CAS  PubMed  Google Scholar 

  24. Sharma HS, Feng L, Lafuente JV, Muresanu DF, Tian ZR, Patnaik R, Sharma A (2015) TiO2-nanowired delivery of mesenchymal stem cells thwarts diabetes-induced exacerbation of brain pathology in heat stroke: an experimental study in the rat using morphological and biochemical approaches. CNS Neurol Disord Drug Targets 14:386–399

    Article  CAS  PubMed  Google Scholar 

  25. Muresanu DF, Sharma A, Tian ZR, Smith MA, Sharma HS (2012) Nanowired drug delivery of antioxidant compound H-290/51 enhances neuroprotection in hyperthermia-induced neurotoxicity. CNS Neurol Disord Drug Targets 11:50–64

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Nanoformulation and nanodelivery program received in part of financial support from the University of Arkansas, Arkansas Bioscience Institute, Arkansas Institute of Nanoscience/Engineering, National Science Foundation, and Howard Hughes Medical Institute are acknowledged. RW thanks help from the HiDEC-UARK, and AO appreciates the support from both Cell/Molecular Biology and Biomedical Engineering. The biological study program is supported by grants from the Air Force Office of Scientific Research (EOARD, London, UK) and Air Force Material Command, USAF, under grant number FA8655-05-1-3065; the National Institutes of Health (R01 AG028679) and Swedish Medical Research Council (nr 2710-HSS); Göran Gustafsson Foundation, Stockholm, Sweden (HSS); AstraZeneca, Mölndal, Sweden (HSS/AS); and Society for the Study of Neuroprotection and Neuroplasticity (SSNN), Romania. The US government is authorized to reproduce and distribute reprints for government purpose notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of the Air Force Office of Scientific Research or the US government.

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, University of Arkansas, Fayetteville, AR, USA

    Asya Ozkizilcik

  2. Institute of Nanoscience and Engineering, University of Arkansas, Fayetteville, AR, USA

    Asya Ozkizilcik, Roger Williams & Z. Ryan Tian

  3. Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR, USA

    Roger Williams & Z. Ryan Tian

  4. Department of Clinical Neurosciences, University of Medicine & Pharmacy, Cluj-Napoca, Romania & “RoNeuro” Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania

    Dafin F. Muresanu

  5. International Experimental Central Nervous System Injury & Repair (IECNSIR), Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, Uppsala University Hospital, Uppsala University, Uppsala, Sweden

    Aruna Sharma & Hari S. Sharma

Authors
  1. Asya Ozkizilcik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roger Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Z. Ryan Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dafin F. Muresanu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Aruna Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hari S. Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hari S. Sharma .

Editor information

Editors and Affiliations

  1. Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy

    Stephen D. Skaper

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media, LLC

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Ozkizilcik, A., Williams, R., Tian, Z.R., Muresanu, D.F., Sharma, A., Sharma, H.S. (2018). Synthesis of Biocompatible Titanate Nanofibers for Effective Delivery of Neuroprotective Agents. In: Skaper, S. (eds) Neurotrophic Factors. Methods in Molecular Biology, vol 1727. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7571-6_35

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-7571-6_35

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7570-9

  • Online ISBN: 978-1-4939-7571-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation