Skip to main content
SpringerLink
Log in

Nanowired-Drug Delivery Enhances Neuroprotective Efficacy of Compounds and Reduces Spinal Cord Edema Formation and Improves Functional Outcome Following Spinal Cord Injury in the Rat

  • Conference paper
  • First Online:
Brain Edema XIV

Part of the book series: Acta Neurochirurgica Supplementum ((NEUROCHIRURGICA,volume 106))

Abstract

The possibility that drugs attached to nanowires enhance their therapeutic efficacy was examined in a rat model of spinal cord injury (SCI). Three Acure compounds AP-173, AP-713 and AP-364 were tagged with TiO2-based nanowires (50–60 nm) and applied over the traumatized cord either 5 or 60 min after SCI in rats produced by a longitudinal incision into the right dorsal horn of the T10-11 segments under equithesin anaesthesia. Normal compounds were used for comparison. After 5 h SCI, behavioral outcome, blood–spinal cord barrier (BSCB) permeability, edema formation and cell injury were examined. Topical application of nanowired compound AP-713 (10 µg in 20 µL) when applied either 5 or 60 min after injury markedly attenuated behavioral dysfunction at 2–3 h after SCI and reduces BSCB disruption, edema formation and cord pathology at 5 h compared to other compounds. Whereas normal compounds applied at 5 min after injury (but not after 60 min) had some significant but less beneficial effects compared to their nanowired combinations. On the other hand, nanowires alone did not influence spinal cord pathology or motor function after SCI. Taken together, our results indicate that the nanowired-drug-delivery enhances the neuroprotective efficacy of drugs in SCI and reduces functional outcome compared to normal compounds even applied at a later stage following trauma, not reported earlier.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Assie MB, Bardin L, Auclair A, Consul-Denjean N, Sautel F, Depoortere R, Newman-Tancredi A (2007) F15063, a potential antipsychotic with dopamine D(2)/D(3) antagonist, 5-HT (1A) agonist and D(4) partial agonist properties: (IV) duration of brain D2-like receptor occupancy and antipsychotic-like activity versus plasma concentration in mice. Naunyn Schmiedebergs Arch Pharmacol Jun 375(4):241–250. Epub 2007 Apr 24

    Google Scholar 

  2. Betbeder D, Sperandio S, Latapie JP, de Nadai J, Etienne A, Zajac JM, Frances B (2000) Biovector nanoparticles improve antinociceptive efficacy of nasal morphine. Pharm Res Jun 17(6):743–748

    Article  CAS  Google Scholar 

  3. Chi B, Victorio ES, Jin T (2007) Synthesis of TiO2-based nanotube on Ti substrate by hydrothermal treatment. J Nanosci Nanotechnol Feb; 7(2):668–672

    Article  CAS  Google Scholar 

  4. Dong W, Zhang T, McDonald M, Padilla C, Epstein J, Tian ZR (2006) Biocompatible nanofiber scaffolds on metal for controlled release and cell colonization. Nanomedicine Dec; 2(4):248–52

    Article  CAS  Google Scholar 

  5. Elliott KAC, Jasper H (1949) Measurement of experimentally induced brain swelling and shrinkage. Am J Physiol 157:122–129

    PubMed  CAS  Google Scholar 

  6. Friese A, Seiller E, Quack G, Lorenz B, Kreuter J (2000) Increase of the duration of the anticonvulsive activity of a novel NMDA receptor antagonist using poly(butylcyanoacrylate) nanoparticles as a parenteral controlled release system. Eur J Pharm Biopharm Mar; 49(2):103–109

    Article  CAS  Google Scholar 

  7. Kreuter J (1995) Nanoparticulate systems in drug delivery and targeting. J Drug Target 3(3):171–173

    Article  PubMed  CAS  Google Scholar 

  8. Olivier JC (2005) Drug transport to brain with targeted nanoparticles. NeuroRx Jan; 2(1):108–119

    Article  Google Scholar 

  9. Sharma HS (2007) Nanoneuroscience: emerging concepts on nanoneurotoxicity and nanoneuroprotection. Nanomedicine Dec; 2(6):753–758. Review

    Google Scholar 

  10. Sharma HS (2005) Neuroprotective effects of neurotrophins and melanocortins in spinal cord injury: an experimental study in the rat using pharmacological and morphological approaches. Ann N Y Acad Sci Aug; 1053:407–1021

    Article  CAS  Google Scholar 

  11. Sharma HS (2005) Pathophysiology of blood–spinal cord barrier in traumatic injury and repair. Curr Pharm Des 11(11):1353–1389. Review

    Google Scholar 

  12. Sharma HS (2004) Pathophysiology of the blood–spinal cord barrier in traumatic injury. In: Sharma HS, Westman J (eds) The blood–spinal cord and brain barriers in health and disease. Elsevier Academic, San Diego, pp 437–518

    Chapter  Google Scholar 

  13. Sharma HS (2008) New perspectives for the treatment options in spinal cord injury. Expert Opin Pharmacother (16):2773–2800. Review.

    Google Scholar 

  14. Sharma HS, Olsson Y (1990) Edema formation and cellular alterations following spinal cord injury in the rat and their modification with p-chlorophenylalanine. Acta Neuropathol (Berl) 79(6):604–610

    Article  CAS  Google Scholar 

  15. Sharma HS, Sharma A (2007) Nanoparticles aggravate heat stress induced cognitive deficits, blood–brain barrier disruption, edema formation and brain pathology. Prog Brain Res 162:245–276

    Article  PubMed  CAS  Google Scholar 

  16. Sharma HS, Skottner A, Lundstedt T, Flardh M, Wiklund L (2006) Neuroprotective effects of melanocortins in experimental spinal cord injury. An experimental study in the rat using topical application of compounds with varying affinity to melanocortin receptors. J Neural Transm Apr; 113(4):463–476

    CAS  Google Scholar 

  17. Sharma HS, Olsson Y, Pearsson S, Nyberg F (1995) Trauma induced opening of the blood–spinal cord barrier is reduced by indomethacin, an inhibitor of prostaglandin synthesis. Experimental observations in the rat using 131I-sodium, Evans blue and lanthanum as tracers. Restor Neurol Neurosci 7:207–215

    PubMed  Google Scholar 

  18. Sharma HS, Olsson Y, Cervós-Navarro J (1993) Early perifocal cell changes and edema in traumatic injury of the spinal cord are reduced by indomethacin, an inhibitor of prostaglandin synthesis. Experimental study in the rat. Acta Neuropathol 85(2):145–153

    Article  PubMed  CAS  Google Scholar 

  19. Sharma HS, Winkler T, Stalberg E, Olsson Y, Dey PK (1991) Evaluation of traumatic spinal cord edema using evoked potentials recorded from the spinal epidural space. An experimental study in the rat. J Neurol Sci Apr; 102(2):150–162

    CAS  Google Scholar 

  20. Sharma HS, Ali SF, Dong W, Tian ZR, Patnaik R, Patnaik S, Sharma A, Boman A, Lek P, Seifert E, Lundstedt T (2007) Drug delivery to the spinal cord tagged with nanowire enhances neuroprotective efficacy and functional recovery following trauma to the rat spinal cord. Ann N Y Acad Sci Dec; 1122:197–218

    Article  CAS  Google Scholar 

  21. Silva GA, Czeisler C, Niece KL, Beniash E, Harrington DA, Kessler JA, Stupp SI (2004) Selective differentiation of neural progenitor cells by high-epitope density nanofibers. Science Feb; 27;303(5662):1352–1355

    Google Scholar 

  22. Vyas TK, Tiwari SB, Amiji MM (2006) Formulation and physiological factors influencing CNS delivery upon intranasal administration. Crit Rev Ther Drug Carrier Syst 23(4):319–347

    Article  PubMed  CAS  Google Scholar 

  23. Wilson B, Samanta MK, Santhi K, Kumar KP, Paramakrishnan N, Suresh B (2008) Poly(n-butylcyanoacrylate) nanoparticles coated with polysorbate 80 for the targeted delivery of rivastigmine into the brain to treat Alzheimer’s disease. Brain Res Mar 20; 1200:159–168. Epub 2008 Jan 26

    Google Scholar 

  24. Yao C, Doose DR, Novak G, Bialer M (2006) Pharmacokinetics of the new antiepileptic and CNS drug RWJ-333369 following single and multiple dosing to humans. Epilepsia Nov 47(11):1822–1829

    Article  CAS  Google Scholar 

  25. Zhao D, Fei Z, Ang WH, Dyson PJ (2006) A strategy for the synthesis of transition-metal nanoparticles and their transfer between liquid phases. Small Jul; 2(7):879–883

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This investigation is partially supported by the Air Force Office of Scientific Research (London), Air Force Material Command, USAF, under grant number FA8655-05-1-3065. The U.S. 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 U.S. Government. We express sincere gratitude to several laboratories where a part of the work is done or some data is recorded and evaluated. Financial support from Acure Pharma (Sweden); Astra-Zeneca, Mölndal, Sweden, Alexander von Humboldt Foundation (Germany); The University Grants Commission, New Delhi, India, Department of Science and Technology, Govt. of India, New Delhi is gratefully acknowledged. The authors have no conflict of interest with any financial agencies mentioned above. Technical assistance of Inga Hörte, Kerstin Flink, Madeleine Jarild, Mari-Anne Carlsson, Margaretta Butler of Uppsala University are highly appreciated.

Author information

Authors and Affiliations

  1. Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anaesthesiology and Intensive Care Medicine, University Hospital, Frödingsgaton 12:28, Uppsala, SE-75421, Sweden

    Hari Shanker Sharma & Aruna Sharma

  2. Neurochemistry Laborartory, Division of Neurotoxicology, National Centre for Toxicological Research/FDA, Jefferson, AR, USA

    Hari Shanker Sharma & Aruna Sharma

  3. Neurochemistry Laboratory, Division of Neurotoxicology, National Centre for Toxicological Research/FDA, Jefferson, AR, USA

    Syed F. Ali

  4. Department of Chemistry and Biochemistry, University of Arkansas Fayetteville, Fayetteville, AR, 72701, USA

    Z. Ryan Tian

  5. Department of Biomedical Engineering, Institute of Technology, Banaras Hindu University, Varanasi, 221 005, India

    R. Patnaik & S. Patnaik

  6. AcurePharma AB, Ulleråkersv 38, Uppsala, Sweden

    Arne Boman, Per Lek, Elisabeth Seifert & Torbjörn Lundstedt

  7. Institutionen för läkemedelskemi, Avdelningen för Organisk farmaceutisk kemi, Uppsala University, Uppsala, Sweden

    Torbjörn Lundstedt

Authors
  1. Hari Shanker Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Syed F. Ali
    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. R. Patnaik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Patnaik
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aruna Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Arne Boman
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Per Lek
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Elisabeth Seifert
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Torbjörn Lundstedt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hari Shanker Sharma .

Editor information

Editors and Affiliations

  1. Medical Research Center, PAN Warszawa, Ceglowska St. 80, Warszawa, 01-809, Poland

    Zbigniew Czernicki

  2. Klinikum Großhadern, Universitätsklinikum München, Marchioninistr. 15, München, 81377, Germany

    Alexander Baethmann

  3. Dept. Neurosurgery, Musashino Red Cross Hospital, Kyonan-cho 1-26-1, Musashino City, Tokyo, 180, Japan

    Umeo Ito

  4. School of Medicine, Nihon University, Oyaguchikami-machi 30-1 , Tokyo, 173-8610, Japan

    Yoichi Katayama

  5. Dept. Neuropathology, Medical Research Institute, Yushima 1-5-45, Tokyo, 113-8510, Japan

    Toshihiko Kuroiwa

  6. Dept. Neurosurgery, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne, NE46BE, United Kingdom

    David Mendelow

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag/Wien

About this paper

Cite this paper

Sharma, H.S. et al. (2010). Nanowired-Drug Delivery Enhances Neuroprotective Efficacy of Compounds and Reduces Spinal Cord Edema Formation and Improves Functional Outcome Following Spinal Cord Injury in the Rat. In: Czernicki, Z., Baethmann, A., Ito, U., Katayama, Y., Kuroiwa, T., Mendelow, D. (eds) Brain Edema XIV. Acta Neurochirurgica Supplementum, vol 106. Springer, Vienna. https://doi.org/10.1007/978-3-211-98811-4_63

Download citation

  • DOI: https://doi.org/10.1007/978-3-211-98811-4_63

  • Published:

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-98758-2

  • Online ISBN: 978-3-211-98811-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation