Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Kaining Zhi
 + 601 word(s) 601 2021-04-16 06:26:00 |
2 format correct
Catherine Yang
 Meta information modification 601 2021-04-27 03:59:21 |

Video Upload Options

We provide professional Video Production Services to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Zhi, K. Blood–Brain Barrier. Encyclopedia. Available online: https://encyclopedia.pub/entry/9024 (accessed on 17 November 2024).
Zhi K. Blood–Brain Barrier. Encyclopedia. Available at: https://encyclopedia.pub/entry/9024. Accessed November 17, 2024.
Zhi, Kaining. "Blood–Brain Barrier" Encyclopedia, https://encyclopedia.pub/entry/9024 (accessed November 17, 2024).
Zhi, K. (2021, April 26). Blood–Brain Barrier. In Encyclopedia. https://encyclopedia.pub/entry/9024
Zhi, Kaining. "Blood–Brain Barrier." Encyclopedia. Web. 26 April, 2021.
Blood–Brain Barrier
Edit
This entry is adapted from the peer-reviewed paper 10.3390/pharmaceutics13040500

The blood–brain barrier (BBB) is a natural obstacle for drug delivery into the human brain, hindering treatment of central nervous system (CNS) disorders such as acute ischemic stroke, brain tumors, and human immunodeficiency virus (HIV)-1-associated neurocognitive disorders.

blood–brain barrier (BBB) PLGA cGMP

1. Blood–Brain Barrier (BBB) and Drug Delivery

Compared with other therapeutic areas, drug development is more challenging for brain diseases such as brain cancers, Alzheimer’s diseases (AD), acute ischemic stroke, and human immunodeficiency virus (HIV)-1-associated neurocognitive disorders (HAND) [1][2][3][4]. Many systemically administered drug products cannot pass the BBB [5]. The BBB restricts the entry of compounds into the central nervous system (CNS) through the presence of brain microvascular endothelial cells, pericytes, perivascular astrocytes, and tight junctions. In addition, the presence of efflux transporters at the BBB has been recognized as a key element to poor drug penetration [6][7]. ATP-binding cassette (ABC) membrane-associated transporters, such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein (MRP1) show significant expressions at the BBB, protecting the brain from potential harmful endogenous and exogenous substances [6][7]. As a result, the BBB only selectively transports molecules such as certain amino acids, sugars, and gaseous molecules (e.g., oxygen and carbon dioxide) into the brain [8]. For example, antiretroviral drugs (ARVs) have shown to be effective in managing HIV-1 [9]. However, due to the inability of ARVs to cross the BBB, they are not highly recommended clinically for the treatment of HAND.

2. Strategies to Cross BBB

Several strategies have been used to improve drug delivery to the brain. Efforts have been made for the development of inhibitors for ABC transporters due to their high expressions on the BBB [2][10][11]. Studies showed that blocking ABC transporters may significantly improve drug penetrations across the BBB. However, this method has not been used clinically due to the wide distribution of ABC transporters throughout the body, the potential toxicity of inhibitors, and unexpected drug–drug interactions [10]. Another approach is the “BBB opening” approach. Opening the BBB can be achieved by using a hyperosmotic solution to shrink the endothelial cells or using certain cytotoxic agents to disrupt the BBB tight junctions [10][11]. However, opening the tight junctions of the BBB is risky clinically because it may also allow the entry of harmful components into the brain and cause side-effects such as seizures and other long-term neurological complications [10]. Moreover, the development of prodrugs to increase their capacity to penetrate the BBB is another potential delivery approach [10]. Prodrugs can be synthesized with sufficient lipophilicity to facilitate the crossing of the endothelial cell membrane and release the parent ARVs into the brain. However, developing prodrugs as a delivery strategy needs a full evaluation of toxicity, cost, and efficacy, as prodrugs are considered to be a separate chemical entity.

A nanoparticle (NP)-based drug delivery system is considered a promising option to improve drug delivery to the brain [3]. NP-based formulations are usually a colloidal system made of polymers, lipids, or other large macromolecules such as albumin. A therapeutic agent may be released through diffusion or erosion of the matrix [12]. The NP-based delivery system can cross the BBB through membrane transcytosis, bypass efflux transporters, and effectively deliver the therapeutic molecule to the CNS [3]. NPs that have been studied for brain delivery include polymeric NPs such as poly(d,l-lactide-co-glycolide) (PLGA) [13][14] and poly(butyl-cyanoacrylate) (PBCA) NPs [15][16], magnetic NPs (MNPs) composed of an iron oxide core [16], lipid-based nanoformulations such as solid lipid nanoparticles (SLN) and liposomes [10][16], and polymeric micelles-based nanoformulations such as Pluronic micelles [10]. Extracellular vesicles (EVs), liposome-like natural carriers, have drawn attention for delivering drugs into the brain as a potential alternative to NPs [17][18][19].

References

  1. Pardridge, W.M. Alzheimer’s disease drug development and the problem of the blood-brain barrier. Alzheimers Dement. 2009, 5, 427–432.
  2. Gomez-Zepeda, D.; Taghi, M.; Scherrmann, J.M.; Decleves, X.; Menet, M.C. ABC Transporters at the Blood-Brain Interfaces, Their Study Models, and Drug Delivery Implications in Gliomas. Pharmaceutics 2019, 12, 20.
  3. Wong, H.L.; Wu, X.Y.; Bendayan, R. Nanotechnological advances for the delivery of CNS therapeutics. Adv. Drug Deliv. Rev. 2012, 64, 686–700.
  4. Bertrand, L.; Nair, M.; Toborek, M. Solving the Blood-Brain Barrier Challenge for the Effective Treatment of HIV Replication in the Central Nervous System. Curr. Pharm. Des. 2016, 22, 5477–5486.
  5. Dong, X. Current Strategies for Brain Drug Delivery. Theranostics 2018, 8, 1481–1493.
  6. Löscher, W.; Potschka, H. Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx 2005, 2, 86–98.
  7. Mahringer, A.; Ott, M.; Reimold, I.; Reichel, V.; Fricker, G. The ABC of the blood-brain barrier—Regulation of drug efflux pumps. Curr. Pharm. Des. 2011, 17, 2762–2770.
  8. Kadry, H.; Noorani, B.; Cucullo, L. A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids Barriers CNS 2020, 17, 69.
  9. Saylor, D.; Dickens, A.M.; Sacktor, N.; Haughey, N.; Slusher, B.; Pletnikov, M.; Mankowski, J.L.; Brown, A.; Volsky, D.J.; McArthur, J.C. HIV-associated neurocognitive disorder--pathogenesis and prospects for treatment. Nat. Rev. Neurol. 2016, 12, 234–248.
  10. Nair, M.; Jayant, R.D.; Kaushik, A.; Sagar, V. Getting into the brain: Potential of nanotechnology in the management of NeuroAIDS. Adv. Drug Deliv. Rev. 2016, 103, 202–217.
  11. Haluska, M.; Anthony, M.L. Osmotic blood-brain barrier modification for the treatment of malignant brain tumors. Clin. J. Oncol. Nurs. 2004, 8, 263–267.
  12. Zhi, K.; Lebo, D.B. A preformulation strategy for the selection of controlled-release components to simulate a subcutaneous implant. Boletín Latinoam. Caribe Plantas Med. Aromáticas 2020, 19, 344–356.
  13. Gong, Y.; Chowdhury, P.; Nagesh, P.K.B.; Rahman, M.A.; Zhi, K.; Yallapu, M.M.; Kumar, S. Novel elvitegravir nanoformulation for drug delivery across the blood-brain barrier to achieve HIV-1 suppression in the CNS macrophages. Sci. Rep. 2020, 10, 3835.
  14. Gong, Y.; Zhi, K.; Nagesh, P.K.B.; Sinha, N.; Chowdhury, P.; Chen, H.; Gorantla, S.; Yallapu, M.M.; Kumar, S. An Elvitegravir Nanoformulation Crosses the Blood-Brain Barrier and Suppresses HIV-1 Replication in Microglia. Viruses 2020, 12, 564.
  15. Patel, T.; Zhou, J.; Piepmeier, J.M.; Saltzman, W.M. Polymeric nanoparticles for drug delivery to the central nervous system. Adv. Drug. Deliv. Rev. 2012, 64, 701–705.
  16. Zhou, Y.; Peng, Z.; Seven, E.S.; Leblanc, R.M. Crossing the blood-brain barrier with nanoparticles. J. Control Release 2018, 270, 290–303.
  17. Zhi, K.; Kumar, A.; Raji, B.; Kochat, H.; Kumar, S. Formulation, manufacturing and regulatory strategies for extracellular vesicles-based drug products for targeted therapy of central nervous system diseases. Expert Rev. Precis. Med. Drug Dev. 2020, 5, 469–481.
  18. Kumar, S.; Zhi, K.; Mukherji, A.; Gerth, K. Repurposing antiviral protease inhibitors using extracellular vesicles for potential therapy of COVID-19. Viruses 2020, 12, 486.
  19. Kumar, A.; Zhou, L.; Zhi, K.; Raji, B.; Pernell, S.; Tadrous, E.; Kodidela, S.; Nookala, A.; Kochat, H.; Kumar, S. Challenges in Biomaterial-Based Drug Delivery Approach for the Treatment of Neurodegenerative Diseases: Opportunities for Extracellular Vesicles. Int. J. Mol. Sci. 2020, 22, 138.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Pharmacology & Pharmacy
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Kaining Zhi
View Times: 726
Revisions: 2 times (View History)
Update Date: 27 Apr 2021
Table of Contents
    1000/1000
    Hot Most Recent
    ScholarVision Creations
    Feedback