Drug delivery to the brain

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Drug delivery to the brain is the process of passing therapeutically active molecules across the blood–brain barrier into the brain. This is a complex process that must take into account the complex anatomy of the brain as well as the restrictions imposed by the special junctions of the blood–brain barrier.

Anatomy

The blood–brain barrier is formed by special

endothelial cells.[1]

Physiology

The main function of the blood–brain barrier is to protect the brain and keep it isolated from harmful toxins that are potentially in the

endothelial cells.[2]
Because of this, the only molecules that are easily able to transverse the blood–brain barrier are ones that are very
endothelial cells makes them a perfect barricade to unspecified particles from entering the brain, working to protect the brain at all costs. Also, because most molecules are transported across the barrier, it does a very effective job of maintaining homeostasis for the most vital organ of the human body.[1]

Drug delivery to the blood–brain barrier

Because of the difficulty for

relative size
.

Problems faced in drug delivery

Other problems persist besides just simply getting through the blood–brain barrier. The first of these is that a lot of times, even if a compound transverses the barrier, it does not do it in a way that the

brain tissue that could render the drug inactive. The drug may be able to pass through the membrane fine, but will be deconstructed once it is inside the brain tissue rendering it useless. All of these are problems that must be addressed and accounted for in trying to deliver effective drug solutions to the brain tissue.[5]

Possible solutions

Exosomes to deliver treatments across the blood–brain barrier

A group from the University of Oxford led by Prof. Matthew Wood claims that exosomes can cross the blood–brain barrier and deliver siRNAs, antisense oligonucleotides, chemotherapeutic agents and proteins specifically to neurons after inject them systemically (in blood). Because these exosomes are able to cross the blood–brain barrier, this protocol could solve the issue of poor delivery of medications to the central nervous system and cure Alzheimer's, Parkinson's Disease and brain cancer, among other diseases. The laboratory has been recently awarded a major new €30 million project leading experts from 14 academic institutions, two biotechnology companies and seven pharmaceutical companies to translate the concept to the clinic.[7][8][9][10]

Pro-drugs

This is the process of disguising medically active molecules with

lipophilic disguise to release the drug into its active form. There are still some major drawbacks to these pro-drugs. The first of which is that the pro-drug may be able to pass through the barrier and then also re-pass through the barrier without ever releasing the drug in its active form. The second is the sheer size of these types of molecules makes it still difficult to pass through the blood–brain barrier.[11]

Peptide masking

Similar to the idea of pro-drugs, another way of masking the drugs

brain tissue. Also if the drug cannot pass back through the blood–brain barrier, it compounds the issues of dosage and intense monitoring would be required. For this to be effective there must be a mechanism for the removal of the active form of the drug from the brain tissue.[7]

Receptor-mediated permabilitizers

These are drug compounds that increase the permeability of the blood–brain barrier.

seizures and the compromised function of the brain.[8]

Nanoparticles

The most promising drug delivery system is using

brain diseases
.

Loaded microbubble-enhanced focused ultrasound

microbubble once it passes through the blood–brain barrier. Studies have shown the effectiveness of this method for getting drugs to specific sites in the brain in animal models.[10]

See also

References

  1. ^ a b c d Neuroscience, Purves et al. Sinauer Associates, Inc. 2008.
  2. doi:10.1146/annurev.neuro.22.1.11
  3. ^ Ramlakhan, N., & Altman, J. (1990). Breaching the Blood–Brain Barrier. New Scientist, 128, 52-52.
  4. ^ a b Seelig, A., Gottschlich, R., & Devant, R. M. (1994). A Method to Determine the Ability of Drugs to Diffuse through the Blood- Brain Barrier. Proceedings of the National Academy of Sciences of the United States of America, 91(1), 68-72.
  5. ^
    doi:10.1016/j.toxlet.2011.06.027
  6. doi:10.1016/0169-409x(96)00011-7
  7. ^ a b c d Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. (2011). Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011 Apr;29(4):341-5. doi: 10.1038/nbt.1807
  8. ^ a b c El-Andaloussi S, Lee Y, Lakhal-Littleton S, Li J, Seow Y, Gardiner C, Alvarez-Erviti L, Sargent IL, Wood MJ.(2011). Exosome-mediated delivery of siRNA in vitro and in vivo. Nat Protoc. 2012 Dec;7(12):2112-26. doi: 10.1038/nprot.2012.131
  9. ^ EL Andaloussi S, Mäger I, Breakefield XO, Wood MJ. (2013). Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013 May;12(5):347-57. doi: 10.1038/nrd3978
  10. ^ a b c d El Andaloussi S, Lakhal S, Mäger I, Wood MJ. (2013). Exosomes for targeted siRNA delivery across biological barriers. Adv Drug Deliv Rev. 2013 Mar;65(3):391-7. doi: 10.1016/j.addr.2012.08.008
  11. ^ Breaching the brain's security system. (2001). Consumers' Research Magazine, 84, 21-21-23.
  12. ^ Secko, D. (2006). Breaking down the blood–brain barrier. Canadian Medical Association. Journal, 174(4), 448-448.
  13. doi:10.1016/j.jconrel.2011.05.010
  14. doi:10.1016/j.ultrasmedbio.2011.04.019
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