Skip to main content
SpringerLink
Log in

Nanopharmaceuticals for the Improved Treatment of Cerebral Stroke

  • Chapter
  • First Online:
Nanobiotechnology in Neurodegenerative Diseases

  • 570 Accesses

Abstract

Stroke remains the leading cause of death and disability across the globe. However, there is a dearth of effective therapy for its treatment. Over the past decade, use of nanomedicine has gained overwhelming interest for the treatment of cerebral stroke due to the constant failure of the conventional treatment. The most widely investigated nanocarriers include neuroprotective agents loaded on functionalized liposomes and polymeric nanoparticles for targeted delivery to the brain, metal oxide nanoparticles, carbon nanotubes, dendrimers, and scaffolds. This chapter will focus on the investigations undertaken hitherto on different types of nanocarriers for delivery of therapeutic agents for the treatment of stroke.

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 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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

Abbreviations

BBB:

Blood–brain barrier

bFGF:

Basic fibroblast growth factor

GBD:

Global Burden of Disease

hEPC:

Human endothelial progenitor cells

MSCs:

Mesenchymal stem cells

PEG:

Polyethylene glycol

PLA:

Poly(lactic acid)

PLGA:

Poly(lactic-co-glycolic acid)

ROS:

Reactive oxygen species

SLN:

Solid lipid nanoparticles

TfR:

Transferrin receptor

tPA:

Tissue plasminogen activator

uPA:

Urokinase-type plasminogen activator

VEGF:

Vascular endothelial growth factor

References

  • Adibhatla RM, Hatcher JF (2008) Tissue plasminogen activator (tPA) and matrix metalloproteinases in the pathogenesis of stroke: therapeutic strategies. CNS Neurol Disord Drug Targets 7:243–253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Agulla J, Brea D, Campos F, Sobrino T, Argibay B, Al-Soufi W, Blanco M, Castillo J, Ramos-Cabrer P (2014) In vivo theranostics at the peri-infarct region in cerebral ischemia. Theranostics 4:90–105. https://doi.org/10.7150/thno.7088

    Article  CAS  Google Scholar 

  • Asahi M, Rammohan R, Sumii T, Wang X, Pauw RJ, Weissig V, Torchilin VP, Lo EH (2003) Antiactin-targeted immunoliposomes ameliorate tissue plasminogen activator-induced hemorrhage after focal embolic stroke. J Cereb Blood Flow Metab 23(8):895–899

    Article  CAS  PubMed  Google Scholar 

  • Astrup J, Symon L, Branston NM, Lassen NA (1977) Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. Stroke 8:51–57

    Article  CAS  PubMed  Google Scholar 

  • Bell BA, Symon L, Branston NM (1985) CBF and time thresholds for the formation of ischemic cerebral edema, and effect of reperfusion in baboons. J Neurosurg 62:31–41

    Article  CAS  PubMed  Google Scholar 

  • Campos-Martorell M, Cano-Sarabia M, Simats A, Hernández-Guillamon M, Rosell A, Maspoch D, Montaner J (2016) Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats. Int J Nanomedicine 11:3035–3048. https://doi.org/10.2147/IJN.S107292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caplan AI (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213:341–347

    Article  CAS  PubMed  Google Scholar 

  • Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98:1076–1084

    Article  CAS  PubMed  Google Scholar 

  • Chung CY, Yang JT, Kuo YC (2013) Polybutylcyanoacrylate nanoparticles for delivering hormone response element-conjugated neurotrophin-3 to the brain of intracerebral hemorrhagic rats. Biomaterials 34:9717–9727

    Article  CAS  PubMed  Google Scholar 

  • Dugan LL, Gabrielsen JK, Yu SP, Lin TS, Choi DW (1996) Buckminsterfullerenol free radical scavengers reduce excitotoxic and apoptotic death of cultured cortical neurons. Neurobiol Dis 3(2):129–135

    Article  CAS  PubMed  Google Scholar 

  • Dugan LL, Turetsky DM, Du C, Lobner D, Wheeler M, Almli CR, Shen CK, Luh TY, Choi DW, Lin TS (1997) Carboxyfullerenes as neuroprotective agents. Proc Natl Acad Sci U S A 94(17):94349439

    Article  Google Scholar 

  • Ellis-Behnke RG, Schneider GE (2011) Peptide amphiphiles and porous biodegradable scaffolds for tissue regeneration in the brain and spinal cord. In: Biomedical Nanotechnology, Methods in molecular biology (Hurst S, vol ed), vol 726. New York, Springer, pp 259–281

    Google Scholar 

  • Estevez AY, Pritchard S, Harper K, Aston JW, Lynch A, Lucky JJ, Ludington JS, Chatani P, Mosenthal WP, Leiter JC, Andreescu S, Erlichman JS (2011) Neuroprotective mechanisms of cerium oxide nanoparticles in a mouse hippocampal brain slice model of ischemia. Free Radic Biol Med 51(6):1155–1163

    Article  CAS  PubMed  Google Scholar 

  • Feigin VL, Norrving B, Mensah GA (2017) Global burden of stroke. Circ Res 120:439–448

    Article  CAS  PubMed  Google Scholar 

  • Ferreira R, Fonseca MC, Santos T, Sargento-Freitas J, Tjeng R, Paiva F, Castelo-Branco M, Ferreirac LS, Bernardino L (2016) Retinoic acid-loaded polymeric nanoparticles enhance vascular regulation of neural stem cell survival and differentiation after ischaemia. Nanoscale. https://doi.org/10.1039/c5nr09077f

    Article  CAS  PubMed  Google Scholar 

  • Fukuta T, Asai T, Oku N (2015) Development of a liposomal drug delivery system for the treatment of ischemic stroke. Drug Deliv Syst 30:309–316

    Article  CAS  Google Scholar 

  • Fukuta T, Asai T, Sato A, Namba M, Yanagida Y, Kikuchi T, Koide H, Shimizu K, Oku N (2016) Neuroprotection against cerebral ischemia/reperfusion injury by intravenous administration of liposomal fasudil. Int J Pharm 506(1–2):129–137

    Article  CAS  PubMed  Google Scholar 

  • Gilmore JL, Yi X, Quan L, Kabanov AV (2008) Novel nanomaterials for clinical neuroscience. J Neuroimmune Pharmacol 3(2):83–94

    Article  PubMed  PubMed Central  Google Scholar 

  • Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D (2008) Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 359:1317–1329

    Article  CAS  PubMed  Google Scholar 

  • Han QQ, Jin W, Xiao ZF, Huang JC, Ni HB, Kong J, Wu J, Chen B, Liang WB, Dai JW (2011) The promotion of neurological recovery in an intracerebral hemorrhage model using fibrin-binding brain derived neurotrophic factor. Biomaterials 32:3244–3252

    Article  CAS  PubMed  Google Scholar 

  • Hatakeyama H, Hatakeyama H, Akita H, Maruyama K, Suhara T, Harashima H (2004) Factors governing the in vivo tissue uptake of transferrin-coupled polyethylene glycol liposomes in vivo. Int J Pharm 281(1–2):25–33

    Article  CAS  PubMed  Google Scholar 

  • Hemphill JC, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, Fung GL, Goldstein JN, Macdonald RL, Mitchell PH, Scott PA, Selim MH, Woo D (2015) Guidelines for the management of spontaneous intracerebral hemorrhage a guideline for healthcare professionals from the American Heart Association/American Stroke Association. American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology. Stroke 46(7):2032–2060

    Article  PubMed  Google Scholar 

  • Ishii T, Fukuta T, Agato Y, Oyama D, Yasuda N, Shimizu K, Kawaguchi AT, Asai T, Oku N (2013) Nanoparticles accumulate in ischemic core and penumbra region even when cerebral perfusion is reduced. Biochem Biophys Res Commun 430:1201–1205

    Article  CAS  PubMed  Google Scholar 

  • Jin HJ, Zhang H, Sun ML, Zhang B-G, Zhang J-W (2013) Urokinase-coated chitosan nanoparticles for thrombolytic therapy: preparation and pharmacodynamics in vivo. J Thromb Thrombolysis 36:458–468

    Article  CAS  PubMed  Google Scholar 

  • Johnson TA, Stasko NA, Matthews JL, Cascio WE, Holmuhamedov EL, Johnson CB, Schoenfisch MH (2010) Reduced ischemia/reperfusion injury via glutathione-initiated nitric-oxide releasing dendrimers. Nitric Oxide 22(1):30–36

    Article  CAS  PubMed  Google Scholar 

  • Kakkar V, Muppu SK, Chopra K, Kaur IP (2013) Curcumin loaded solid lipid nanoparticles: an efficient formulation approach for cerebral ischemic reperfusion injury in rats. Eur J Pharm Biopharm 85:339–345

    Article  CAS  PubMed  Google Scholar 

  • Kamat S, Michelson A, Benoit S, Hacke W, Kaste M, Fieschi C (1996) Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 334:1405–1406

    Article  Google Scholar 

  • Kawaguchi AT, Yamano M, Haida M, Ohba H, Kakiuchi T, Tsukada H (2017) Effect of oxygen affinity of liposome-encapsulated hemoglobin on cerebral ischemia and reperfusion as detected by positron emission tomography in nonhuman primates. Artif Organs 41:336–345. https://doi.org/10.1111/aor.12905

    Article  CAS  PubMed  Google Scholar 

  • Krol S, Macrez R, Docagne F, Defer G, Laurent S, Rahman M, Hajipour MJ, Kehoe PG, Mahmoudi M (2013) Therapeutic benefits from nanoparticles: the potential significance of nanoscience in diseases with compromise to the blood brain barrier. Chem Rev 113:1877–1903

    Article  CAS  PubMed  Google Scholar 

  • Kubinova S, Sykova E (2010) Nanotechnology for treatment of stroke and spinal cord injury. Nanomedicine 5:99–108

    Article  CAS  PubMed  Google Scholar 

  • Lin BL, Zhang JZ, Lu LJ, Mao JJ, Cao MH, Mao XH, Zhang F, Duan XH, Zheng CS, Zhang LM, Shen J (2017) Superparamagnetic iron oxide nanoparticles-complexed cationic amylose for in vivo magnetic resonance imaging tracking of transplanted stem cells in stroke. Nano 7:107. https://doi.org/10.3390/nano7050107

    Article  CAS  Google Scholar 

  • Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79:1431–1568

    Article  CAS  PubMed  Google Scholar 

  • Loscher W, Potschka H (2005) Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases. Prog Neurobiol 76(1):22–76

    Article  PubMed  CAS  Google Scholar 

  • Lovat V, Pantarotto D, Lagostena L, Cacciari B, Grandolfo M, Righi M, Spalluto G, Prato M, Ballerini L (2005) Carbon nanotube substrates boost neuronal electrical signaling. Nano Lett 5(6):1107–1110

    Article  CAS  PubMed  Google Scholar 

  • Luo Z, Zhang S (2012) Designer nanomaterials using chiral selfassembling peptide systems and their emerging benefit for society. Chem Soc Rev 41(13):4736–4754

    Article  CAS  PubMed  Google Scholar 

  • Massobrio G, Massobrio P, Martinoia S (2008) Modeling the neuron-carbon nanotube-ISFET junction to investigate the electrophysiological neuronal activity. Nano Lett 8(12):4433–4440

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto K, Sato C, Naka Y, Whitby R, Shimizu N (2010) Stimulation of neuronal neurite outgrowth using functionalized carbon nanotubes. Nanotechnology 21(11):115101

    Article  CAS  PubMed  Google Scholar 

  • Mayer SA, Rincon F (2005) Treatment of intracerebral haemorrhage. Lancet Neurol 4:662–672

    Article  PubMed  Google Scholar 

  • Mazzatenta A, Giugliano M, Campidelli S, Gambazzi L, Businaro L, Markram H, Prato M, Ballerini L (2007) Interfacing neurons with carbon nanotubes: electrical signal transfer and synaptic stimulation in cultured brain circuits. J Neurosci 27(26):6931–6936

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moon SU, Kim J, Bokara KK, Kim JY, Khang D, Webster TJ, Lee JE (2012) Carbon nanotubes impregnated with subventricular zone neural progenitor cells promotes recovery from stroke. Int J Nanomedicine 7:2751–2765. https://doi.org/10.2147/IJN.S30273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Després JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB (2015) Executive summary: heart disease and stroke statistics—2015 update a report from the American Heart Association. Circulation 131:434–441

    Article  Google Scholar 

  • Nance EA, Woodworth GF, Sailor KA (2012) A dense poly (ethylene glycol) coating improves penetration of large polymeric nanoparticles within brain tissue. Science Trans Med 4:149ra119

    Article  CAS  Google Scholar 

  • Partoazar A, Nasoohi S, Rezayat SM, Gilani K, Mehr SE, Amani A, Rahimi N, Dehpour AR (2017) Nano liposome containing cyclosporine A reduced neuroinflammationresponsesandimprovedneurologicalactivitiesincerebralischemia/reperfusion in rat. Fundam Clin Pharmacol 31:185–193. https://doi.org/10.1111/fcp.12244

    Article  CAS  PubMed  Google Scholar 

  • Peng T, Britton GL, Kim H, Cattano D, Aronowski J, Grotta J, McPherson DD, Huang SL (2013) Therapeutic time window and dose dependence of xenon delivered via echogenic liposomes for neuroprotection in stroke. CNS Neurosci Ther 19(10):773–784

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sang LY-H, Liang YX, So KF, Leung GK-K, Ellis-Behnke RG, Cheung RT-F (2014) A self-assembling nanomaterial reduces acute brain injury and enhances functional recovery in a rat model of hypertensive intracerebral hemorrhage. J Nanomed Nanotechnol 5:1

    Google Scholar 

  • Schubert D, Dargusch R, Raitano J, Chan SW (2006) Cerium and yttrium oxide nanoparticles are neuroprotective. Biochem Biophys Res Commun 342(1):86–91

    Article  CAS  PubMed  Google Scholar 

  • Takamiya M, Miyamoto Y, Yamashita T, Deguchi K, Ohta Y, Abe K (2012) Strong neuroprotection with a novel platinum nanoparticle against ischemic stroke- and tissue plasminogen activator-related brain damages in mice. Neuroscience 221:47–55

    Article  CAS  PubMed  Google Scholar 

  • Taskin E, Ozcan K, Canacankatan N, Satar M, Yapicioglu HY, Erdogan S (2009) The effects of indomethacin on caspases, glutathione level and lipid peroxidation in the newborn rats with hypoxic-ischemic cerebral injury. Brain Res 1289:118–123

    Article  CAS  PubMed  Google Scholar 

  • Thwaites JW, Reebye V, Mintz P, Levicar N, Habib N (2012) Cellular replacement and regenerative medicine therapies in ischemic stroke. Regen Med 7:387–395

    Article  CAS  PubMed  Google Scholar 

  • Tiebosch IA, Crielaard BJ, Bouts MJ, Zwartbol R, Salas-Perdomo A, Lammers T, Planas AM, Storm G, Dijkhuizen RM (2012) Combined treatment with recombinant tissue plasminogen activator and dexamethasone phosphate-containing liposomes improves neurological outcome and restricts lesion progression after embolic stroke in rats. J Neurochem 123(Suppl. 2):65–74. https://doi.org/10.1111/j.1471-4159.2012.07945

    Article  CAS  PubMed  Google Scholar 

  • Torno MD, Kaminski MD, Xie Y, Meyers RE, Mertz CJ, Liu X, O’Brien WD Jr, Rosengart AJ (2008) Improvement of in vitro thrombolysis employing magnetically-guided microspheres. Thromb Res 121:799–811

    Article  CAS  PubMed  Google Scholar 

  • Trounson A, McDonald C (2015) Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell 17:11–22

    Article  CAS  PubMed  Google Scholar 

  • Vani JR, Mohammadi MT, Foroshani MS, Jafari M (2016) Polyhydroxylated fullerene nanoparticles attenuate brain infarction and oxidative stress in rat model of ischemic stroke. EXCLI J 15:378–390. https://doi.org/10.17179/excli2016-309

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Tang M (2018) Dysfunction of various organelles provokes multiple cell death after quantum dot exposure. Int J Nanomedicine 13:2729–2742. https://doi.org/10.2147/IJN.S157135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang LC, Zhang QG, Zhou CF, Yang F, Zhang YD, Wang RM, Brann DW (2010) Extra-nuclear estrogen receptors mediate the neuroprotective effects of estrogen in the rat hippocampus. PLoS One 5(5):e9851

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang S, Gelain F, Zhao X (2005) Designer self-assembling peptide nanofiber scaffolds for 3D tissue cell cultures. Semin Cancer Biol 15(5):413–420

    Article  PubMed  Google Scholar 

  • Zhao H, Bao XJ, Wang RZ, Li GL, Gao J, Ma SH, Wei JJ, Feng M, Zhao YJ, Ma WB, Yang Y, Li YN, Kong YG (2011) Postacute ischemia vascular endothelial growth factor transfer by transferrin-targeted liposomes attenuates ischemic brain injury after experimental stroke in rats. Hum Gene Ther 22(2):207–215

    Article  CAS  PubMed  Google Scholar 

  • Zheng S, Bai YY, Liu Y, Gao X, Li Y, Changyi Y, Wang Y, Chang D, Ju S, Li C (2015) Salvaging brain ischemia by increasing neuroprotectant uptake via nanoagonist mediated blood brain barrier permeability enhancement. Biomaterials 66:920

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pharmaceutical Education and Research, Wardha, Maharashtra, India

    Shagufta Khan

  2. SVKM’s Institute of Pharmacy, Dhule, Maharashtra, India

    Aarti Belgamwar

  3. Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India

    Pramod Yeole

Authors
  1. Shagufta Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aarti Belgamwar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pramod Yeole
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Nanobiotechnology Laboratory, Department of Biotechnology, SGB Amravati University, Amravati, Maharashtra, India, Department of Chemistry, Federal University of Piauí, Teresina, Piauí, Brazil

    Mahendra Rai

  2. Nanobiotechnology Laboratory, Department of Biotechnology, SGB Amravati University, Amravati, Maharashtra, India

    Alka Yadav

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Khan, S., Belgamwar, A., Yeole, P. (2019). Nanopharmaceuticals for the Improved Treatment of Cerebral Stroke. In: Rai, M., Yadav, A. (eds) Nanobiotechnology in Neurodegenerative Diseases. Springer, Cham. https://doi.org/10.1007/978-3-030-30930-5_15

Download citation

Publish with us

Policies and ethics

Search

Navigation