, Volume 26, Issue 3, pp 675–684 | Cite as

Enhancement of drug permeability across blood brain barrier using nanoparticles in meningitis

  • Keerthi G. S. Nair
  • Velmurugan Ramaiyan
  • Sathesh Kumar Sukumaran


The central nervous system, one of the most delicate microenvironments of the body, is protected by the blood–brain barrier regulating its homeostasis. Blood–brain barrier is a highly complex structure that tightly regulates the movement of ions of a limited number of small molecules and of an even more restricted number of macromolecules from the blood to the brain, protecting it from injuries and diseases. However, the blood–brain barrier also significantly precludes the delivery of drugs to the brain, thus, preventing the therapy of a number of neurological disorders. As a consequence, several strategies are currently being sought after to enhance the delivery of drugs across the blood–brain barrier. Within this review a brief description of the structural and physiological features of the barriers and the recently born strategy of brain drug delivery based on the use of nanoparticles are described. Finally, the future technological approaches are described. The strong efforts to allow the translation from preclinical to concrete clinical applications are worth the economic investments.


Meningitis Blood–brain barrier Nanoparticles Drug delivery 



The authors wish to thank Vels Institute of Science Technology and Advanced Studies (VISTAS) for supporting this review work.

Compliance with ethical standards

Conflict of interest

The authors declared no conflict of interest.


  1. Acevedo R et al (2014) Bacterial outer membrane vesicles and vaccine applications. Front Immunol 5:121CrossRefPubMedPubMedCentralGoogle Scholar
  2. Adamson RH, Lenz JF, Zhang X et al (2004) Oncotic pressures opposing filtration across non-fenestrated rat micro vessels. J Physiol 557:889–907CrossRefPubMedPubMedCentralGoogle Scholar
  3. Afergan E, Epstein H, Dahan R (2008) Delivery of serotonin to the brain by monocytes following phagocytosis of liposomes. J Control Release 132:84–90CrossRefPubMedGoogle Scholar
  4. Andersen AJ, Hashemi SH, Galimberti G et al (2010) The interaction of complement system with abeta-binding liposomes: towards engineering of safer vesicles for the management of Alzheimer’s disease. J Biotechnol 150:97–98CrossRefGoogle Scholar
  5. Antinori A, Cingolani A, Giancola ML et al (2003) Clinical implications of HIV-1 drug resistance in the neurological compartment. Scand J Infect Dis Suppl 106:41–44CrossRefPubMedGoogle Scholar
  6. Bae YH, Na K, Lee ES (2010) PH Sensitive polymeric miscelles for drug delivery. US 7659314 B2Google Scholar
  7. Baker JR (2010) Dendrimer conjugates. US 20100160299 A1Google Scholar
  8. Barenholz Y, Ovadia H, Kizelsztein P (2011) Liposomal formulations comprising an amplhipathic weak base like tempamine for treatment of neurodegenerative conditions. US 20110027351 A1Google Scholar
  9. Broadwell RD (1989) Transcytosis of macromolecules through the blood–brain barrier: a cell biological perspective and critical appraisal. Acta Neuropathol 79:117–128CrossRefPubMedGoogle Scholar
  10. Cui B, Wu C, Chen L (2007) One at a time live tracking of NGF axonal transport using quantum dots. Proc Natl Acad Sci USA 104:13666–13671CrossRefPubMedPubMedCentralGoogle Scholar
  11. De Vries HE, de Boervan KA, Berkel TJC, Breimer DD (1997) The blood–brain barrier in neuroinflammatory diseases. Pharmacol Res 49:143–155Google Scholar
  12. Dinda SC, Pattnaik G (2013) Nano biotechnology-based drug delivery in brain targeting. Curr Pharm Biotechnol 14:1264–1274CrossRefPubMedGoogle Scholar
  13. Fischer H, Gottschlich R, Seelig A (1998) Blood–brain barrier permeation molecular parameters governing passive diffusion. J Membr Biol 165:201–211CrossRefPubMedGoogle Scholar
  14. Fulmer T (2009) Nanoparticles vs bacteria. Sci BX 2Google Scholar
  15. Gabathuler R (2010) Approaches to transport therapeutic drugs across the blood–brain barrier to treat brain diseases. Neurobiol Dis 37:48–57CrossRefPubMedGoogle Scholar
  16. Ghose AK, Viswanadhan VN, Wendoloski JJ (1999) A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. J Comb Chem 1:55–68CrossRefPubMedGoogle Scholar
  17. Re F, Gregori FM, Masserini M (2012) Nanotechnology for neurodegenerative disorders, Nanomedicine 8:51–58CrossRefGoogle Scholar
  18. Haque S, Kaur Sahni J, Baboota S et al (2011) Nanomedicines for brain targeting: a patent review. Recent Pat Nanomed 1:14961Google Scholar
  19. Haque S, Alam S, Sahni JK et al (2012) Nanostructure-based drug delivery systems for brain targeting. Dev Ind Pharm 38:387–411CrossRefGoogle Scholar
  20. Holmes D (2013) The next big things are tiny. Lancet Neurol 12:31–32CrossRefPubMedGoogle Scholar
  21. Honjo K, Black SE, Verhoeff NP (2012) Alzheimer’s disease, cerebrovascular disease, and the β-amyloid cascade. Can J Neurol Sci 39:712–728CrossRefPubMedGoogle Scholar
  22. Jain KK (2012) Nanobiotechnology-based strategies for crossing the blood–brain barrier. Nanomed 7:1225–1233CrossRefGoogle Scholar
  23. Jaiswal RR (2014) Nanoparticle and laser based new meningitis test. Nanotechnol SciGoogle Scholar
  24. Kandanearatchi A, Williams B, Everall IP (2003) Assessing the efficacy of highly active antiretroviral therapy in the brain. Brain Pathol 13:104–110CrossRefPubMedGoogle Scholar
  25. Khanbabaie R, Jahanshahi M (2012) Revolutionary impact of nanodrug delivery on neuroscience. Curr Neuropharmacol 10:370–392CrossRefPubMedPubMedCentralGoogle Scholar
  26. Kotze AF, Lueßen HL, Leeuw BJ et al (1998) Comparison of the effect of different chitosan salts and N-trimethyl chitosan chloride on the permeability of intestinal epithelial cells (Caco-2). J Control Release 51:35–46CrossRefPubMedGoogle Scholar
  27. Kumagai AK, Eisenberg JB, Pardridge WM (1987) Absorptive-mediated endocytosis of cationized albumin and a -endorphin-cationized albumin chimeric peptide by isolated brain capillaries. Model system of blood–brain barrier transport. J Biol Chem 262:15214–15219PubMedGoogle Scholar
  28. Lieb WR, Stein WD (1986) NonStokesian nature of transverse diffusion within human red cell membranes. J Membr Biol 92:111–119CrossRefPubMedGoogle Scholar
  29. Lipinski CA (2000) Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods 44:235–249CrossRefPubMedGoogle Scholar
  30. Liu L, Kaijin X, Wang H et al (2009) Self-assembled cationic peptide nanoparticles as an efficient antimicrobial agent. Nat Nanotechnol 4:457–463CrossRefPubMedGoogle Scholar
  31. Lloyd K, Hornykiewicz O (1970) Parkinson’s disease activity of l-dopa decarboxylase in discrete brain regions. Science 170:1212–1213CrossRefPubMedGoogle Scholar
  32. Martin-Banderas L, Holgado MM, Venero JL et al (2011) Nanostructures for drug delivery to the brain. Curr Med Chem 148:5303–5321CrossRefGoogle Scholar
  33. Montet X, Funovics M, Montet-Abou K et al (2006) Multivalent effects of RGD peptides obtained by nanoparticle display. J Med Chem 49:6087–6093CrossRefPubMedGoogle Scholar
  34. Muro S, Kova M, Muzykantov V (2004) Endothelial endocytic pathways: gates for vascular drug delivery. Curr Vasc Pharmacol 2:281–299CrossRefPubMedGoogle Scholar
  35. Nan X, Julin G et al (2011) Efficacy of intravenous amphotericin B-polybutylcyanoacrylate nanoparticles against cryptococcal meningitis in mice. Int J Nanomed 6:905–913Google Scholar
  36. Nelson T, Quattrone A, Alkon D (2010) Artificial low density lipoprotein carriers for transport of substances across the blood brain barrier. US 7682627 B2Google Scholar
  37. Netter FH (2006) Atlas of human anatomy, 4th edn. Saunders Elsevier, PhiladelphiaGoogle Scholar
  38. Papisov MI, Belov V, Gannon K (2013) Physiology of the intrathecal bolus: the leptomeningeal route for macromolecule and particle delivery to CNS. Mol Pharmacol 6:1522–1532CrossRefGoogle Scholar
  39. Pardridge WM (2001) Brain drug targeting: the future of brain drug development. Cambridge University Press, CambridgeCrossRefGoogle Scholar
  40. Petkar KC, Chavhan SS, Agatonovik-Kustrin S et al (2011) Nanostructured materials in drug and gene delivery: a review of the state of the art. Crit Rev Ther Drug Carrier Syst 28:101–164CrossRefPubMedGoogle Scholar
  41. Provenzale JM, Silva GA (2009) Uses of nanoparticles for central nervous system imaging and therapy. Am J Neuroradiol 30:1293–1301CrossRefPubMedGoogle Scholar
  42. Reddy J (2010) Preventive and therapeutic vaccine for alzheimer’s disease. US 20100173004 A1Google Scholar
  43. Rosenstein NE, Perkins BA, Stephens DS, Popovic T, Hughes JM (2001) Meningococcal disease. N Engl J Med 344:1378–1388CrossRefPubMedGoogle Scholar
  44. Sadekar S, Ghandehari H (2012) Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery. Adv Drug Deliv Rev 64:571–588CrossRefPubMedGoogle Scholar
  45. Saraiva C, Praça C, Ferreira R et al (2016a) Nanoparticle-mediated brain drug delivery: overcoming blood–brain barrier to treat neurodegenerative diseases. J Control Release 235:34–47CrossRefPubMedGoogle Scholar
  46. Saraiva C, Praça Ferreira R, Santos T et al (2016b) Nanoparticle-mediated brain drug delivery: overcoming blood–brain barrier to treat neurodegenerative diseases. J Control Release 10:34–47CrossRefGoogle Scholar
  47. Schwarz J, Weisspapir M (2006) Colloidal solid lipid vehicle for pharmaceutical use. US 20060222716 A1Google Scholar
  48. Simko M, Fiedeler U, Gesso A, Nentwich M (2010) Can nanoparticles end up in the brain? Nano Trust Dossiers (014en) Assessed 12 Oct 2017
  49. Soni S, Ruhela RK, Medhi B (2016) Nanomedicine in central nervous system disorders: a present and future prospective. Adv Pharm Bull 6:319–335CrossRefPubMedPubMedCentralGoogle Scholar
  50. Stenehjem DD, Hartz AM, Bauer B et al (2009) Novel and emerging strategies in drug delivery for overcoming the blood–brain barrier. Future Med Chem 1:1623–1641CrossRefPubMedGoogle Scholar
  51. Suman (2011) Nanomaterials help in early diagnosis of meningitis. Nano Werk spot lightGoogle Scholar
  52. Sung HW, Lin YH, Chen MC et al (2007) Nanoparticles for drug delivery. US 20070237827 A1Google Scholar
  53. Taylor E, Webster TJ (2011) Reducing infection s through nanotechnology and nanoaprticles. Int J Nanomed 6:1463–1473CrossRefGoogle Scholar
  54. Tortora GJ, Derrickson B (2009) Principles of anatomy and physiology, 12th edn. John Wiley & Sons Inc., DanverGoogle Scholar
  55. Trauble H (1971) The movement of molecules across lipid membranes: a molecular theory. J Membr Biol 4:193–208CrossRefPubMedGoogle Scholar
  56. Treat LH, McDannold N, Zhang Y et al (2012) Improved anti-tumor effect of liposomal doxorubicin after targeted blood–brain barrier disruption by MRI-guided focused ultrasound in rat glioma. Ultrasound Med Biol 38:1716–1725CrossRefPubMedPubMedCentralGoogle Scholar
  57. Varela JN, Amstalden MC, Pereira RF et al (2014) Haemophilus influenzae porine ompP2 gene transfer mediated by graphene oxide nanoparticles with effects on transformation process and virulence bacterial capacity. J Nanobiotechnol 16:12–14Google Scholar
  58. World Health Organization (1988) Control of epidemic meningococcal disease, Second edn. WHO Practical Guidelines, Geneva Google Scholar
  59. Wu J, Wang C, Sun J et al (2011) Neurotoxicity of silica nanoparticles: brain localization and dopaminergic neurons damage pathways. ACS Nano 5:4476–4489CrossRefPubMedGoogle Scholar
  60. Youns M, Hoheisel JD, Efferth T (2011) Therapeutic and diagnostic applications of nanoparticles. Curr Drug Targets 12:357–365CrossRefPubMedGoogle Scholar
  61. Zhang TT, Li W, Meng G, Wang P, Liao W (2016) Strategies for transporting nanoparticles across the blood–brain barrier. Biomater Sci 4:219–229CrossRefPubMedGoogle Scholar
  62. Zivadinov R, Zorzon M, Tommasi MA, Nasuelli D, Bernardi M, Monti-Bragadin L (2003) A longitudinal study of quality of life and side effects in patients with multiple sclerosis treated with interferon. J Neurol Sci 216:113–118CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pharmaceutics, School of Pharmaceutical SciencesVels Institute of Science, Technology and Advanced Studies (VISTAS)ChennaiIndia

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