Open Access Open Access  Restricted Access Subscription or Fee Access

Current Trends in Crossing the Blood–Brain Barrier: A Review

Chenna M Shalini, Komati Manasa, Zafar Khan, Manga Meghana, Rama Rao T

Abstract


The blood-brain barrier (BBB) is a protective barrier that protects the central nervous system (CNS) from toxins and pathogens in the blood. However, the existence of BBB challenges therapy for CNS diseases and disorders as most pharmaceuticals (drugs) are restricted to enter brain. The review article focuses on the approaches involved to cross BBB with various advanced technology such as nanoparticles, intraventricular injection, chemical modifications, virus mediated distribution, exosome mediated transport, drug penetration enhancers, liposome based strategies, brain permeability enhancers, micro emulsions and micelles, cell penetrating peptides dendrimers and colloidal active ingredients. This study's objective is to provide a broad overview of recent developments in the delivery of brain medications as well as related subjects. We hope that this review will encourage readers to think about new approaches to brain drug delivery. Traditional oral or systemic administrations of therapeutic medications are limited in their ability to treat some central nervous system illness, including various types of cerebral malignances due to potential serious side effects and/or lack of brain penetration of medications decreases.

Keywords


Blood Brain Barrier, Medication delivery, central nervous system, saturation, nanotechnology, active targeting, Nanoparticle.

Full Text:

PDF

References


Ehrlich P. Das sauerstufbudurfnis des organismus. In: Eine Farbenanalytische Studie. Berlin: Hirschwald; 1885.

Goldmann E. Vitalfärbung am zentralnervensystem. Abhandl Königl preuss Akad Wiss 1; 1913.

Reese TS, Karnovsky MJ. Fine structural localization of a blood–brain barrier to exogenous peroxidase. J Cell Biol 1967; 34:207–17 [4] Oldendorf WH, Cornford ME, Brown WJ. The large apparent work capability of the blood–brain barrier: a study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat. Ann Neurol1977;1:409–17,

Daneman R, Zhou L, Kebede AA, Barres BA. Pericytes are required for blood–brain barrier integrity during embryogenesis. Nature 2010;468:562–6,

Shepro D, Morel NM. Pericyte physiology. FASEB J 1993;7:1031–8 [7] Hamilton NB, Attwell D, Hall CN. Pericyte-mediated regulation of capillary diameter: a component of neurovascular coupling in health and disease. Front Neuroenerg 2010;2.

PardridgeWM. The blood–brain barrier: bottleneck in brain drug development. NeuroRx 2005;2:3–14.

Laschinger M, Engelhardt B. Interaction of alpha4-integrin with VCAM-1 is involved in adhesion of encephalitogenic T cell blasts to brain endothelium but not in their transendothelial migration in vitro. J Neuroimmunol 2000; 102:32–43

Greenwood J, Amos CL, Walters CE, Couraud P-O, Lyck R, Engelhardt B, et al. Intracellular domain of brain endothelial intercellular adhesion molecule-1 is essential for T lymphocyte-mediated signaling and migration. J Immunol 2003; 171:2099–108. [11] Reese TS, Karnovsky MJ: Fine structural localization of a blood brain barrier to exogenous peroxidase. J Cell Biol 1967, 34:207-217. [12] Banks WA: Are the extracellular pathways a conduit for the delivery of therapeutics to the brain? Curr Pharm Des 2004, 10:1365-1370.

Broadwell RD: Transcytosis of macromolecules through the blood-brain barrier: a cell biological perspective and critical appraisal. Acta Neuropathol 1989, 79:117-128

Begley DJ: ABC transporters and the blood-brain barrier. Curr Pharm Des 2004, 10:1295-1312.

Davson H, Welch K, Segal MB: Some special aspects of the blood-brain barrier. In The Physiology and Pathophysiology of the Cerebrospinal Fluid Edinburgh: Churchill Livingstone; 1987:247-374 [16] Banks WA, Moinuddin A, Morley JE: Regional transport of TNF-α across the blood-brain barrier in young ICR and young and aged SAMP8 mice. Neurobiol Aging 2001, 22:671-676

Gao, X.P.; Kouklis, P.; Xu, N.; Minshall, R.D.; Sandoval, R.; Vogel, S.M.; Malik, A.B. Reversibility of increased microvessel permeability in response to VE-cadherin disassembly. Am. J. Physiol. Lung Cell. Mol. Physiol. 2000, 279, L1218–L1225.

Rosenberg, G.A. Blood-Brain Barrier Permeability in Aging and Alzheimer’s Disease. J. Prev. Alzheimers Dis. 2014, 1, 138–139.

Van Tellingen, O.; Yetkin-Arik, B.; de Gooijer, M.C.; Wesseling, P.; Wurdinger, T.; de Vries, H.E. Overcoming the blood-brain tumor barrier for effective glioblastoma treatment. Drug Resist. Updates 2015, 19, 1–12.

Kooij, G.; van Horssen, J.; Bandaru, V.V.; Haughey, N.J.; de Vries, H.E. The Role of ATP-Binding Cassette Transporters in Neuro-Inflammation: Relevance for Bioactive Lipids. Front. Pharmacol. 2012, 3, 74.

Thomas, C.; Tampe, R. Structural and Mechanistic Principles of ABC Transporters. Annu. Rev. Biochem. 2020, 89, 605–636.

Hotz, J.M.; Thomas, J.R.; Katz, E.N.; Robey, R.W.; Horibata, S.; Gottesman, M.M. ATP-binding cassette transporters at the zebrafish blood-brain barrier and the potential utility of the zebrafish as an in vivo model. Cancer Drug Resist. 2021, 4, 620–633.

Lai, J.I.; Tseng, Y.J.; Chen, M.H.; Huang, C.Y.F.; Chang, P.M.H. Clinical Perspective of FDA Approved Drugs with P-Glycoprotein Inhibition Activities for Potential Cancer Therapeutics. Front. Oncol. 2020, 10, 2336.

Kakkis, E.D.; Muenzer, J.; Tiller, G.E.; Waber, L.; Belmont, J.; Passage, M.; Izykowski, B.; Phillips, J.; Doroshow, R.; Walot, I.; et al. Enzyme-replacement therapy in mucopolysaccharidosis I. N. Engl. J. Med. 2001, 344, 182–188.

Muenzer, J.; Hendriksz, C.J.; Fan, Z.; Vijayaraghavan, S.; Perry, V.; Santra, S.; Solanki, G.A.; Mascelli, M.A.; Pan, L.Y.; Wang, N.; et al. A phase I/II study of intrathecal idursulfase-IT in children with severe mucopolysaccharidosis II. Genet. Med. 2016, 18, 73–81

[10:33 am, 14/09/2023PS: 71.Kakkis, E.D.; Muenzer, J.; Tiller, G.E.; Waber, L.; Belmont, J.; Passage, M.; Izykowski, B.; Phillips, J.; Doroshow, R.; Walot,I.;etal.Enzyme-replacement therapy in mucopolysaccharidosis I. N. Engl. J. Med. 2001, 344, 182–188

Egleton, R.D.; Davis, T.P. Development of neuropeptide drugs that cross the blood-brain barrier. NeuroRx J. Am. Soc. Exp. NeuroTher. 2005, 2, 44–53

Terstappen, G.C.; Meyer, A.H.; Bell, R.D.; Zhang, W.D. Strategies for delivering therapeutics across the blood-brain barrier. Nat.Rev. Drug Discov. 2021, 20, 362–383

Pulgar, V.M. Transcytosis to Cross the Blood Brain Barrier, New Advancements and Challenges. Front. Neurosci. 2019, 12, 1019

Elliott, R.O.; He, M. Unlocking the Power of Exosomes for Crossing Biological Barriers in Drug Delivery. Pharmaceutics 2021,13, 122.

Penfornis, P.; Vallabhaneni, K.C.; Whitt, J.; Pochampally, R. Extracellular vesicles as carriers of microRNA, proteins and lipids in tumor microenvironment. Int. J. Cancer 2016, 138.

Armstrong, J.P.K.; Holme, M.N.; Stevens, M.M. Re-Engineering Extracellular vesicles as Smart Nanoscale Therapeutics. Acs Nano2017, 11, 69–83

Hjouj, M.; Last, D.; Guez, D.; Daniels, D.; Sharabi, S.; Lavee, J.; Rubinsky, B.; Mardor, Y. MRI Study on Reversible and Irreversible Electroporation Induced Blood Brain Barrier Disruption. PLoS ONE 2012, 7, e42817

Vagner, T.; Dvorzhak, A.; Wojtowicz, A.M.; Harms, C.; Grantyn, R. Systemic application of AAV vectors targeting GFAP-expressing astrocytes in Z-Q175-KI Huntington’s disease mice. Mol. Cell. Neurosci. 2016, 77, 76–86

Serlin Y, Shelef I, Knyazer B, Friedman A. Anatomy and physiology of the blood-brain barrier. Semin Cell Dev Biol. 2015 Feb;38:2-6. doi: 10.1016/j.semcdb.




DOI: https://doi.org/10.37591/tdd.v10i2.1342

Refbacks

  • There are currently no refbacks.


Copyright (c) 2023 Trends in Drug Delivery