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Cited by 68Epilepsy research and treatmentBarrier Structure and Function StudiesAdvanced Drug Delivery Systems

Bypassing the Blood–Brain Barrier: Direct Intracranial Drug Delivery in Epilepsies

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Gernert, Manuela, Feja, Malte·2020·Pharmaceutics
DOI 10.3390/pharmaceutics12121134PMC PMC7760299
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Abstract

Epilepsies are common chronic neurological diseases characterized by recurrent unprovoked seizures of central origin. The mainstay of treatment involves symptomatic suppression of seizures with systemically applied antiseizure drugs (ASDs). Systemic pharmacotherapies for epilepsies are facing two main challenges. First, adverse effects from (often life-long) systemic drug treatment are common, and second, about one-third of patients with epilepsy have seizures refractory to systemic pharmacotherapy. Especially the drug resistance in epilepsies remains an unmet clinical need despite the recent introduction of new ASDs. Apart from other hypotheses, epilepsy-induced alterations of the blood–brain barrier (BBB) are thought to prevent ASDs from entering the brain parenchyma in necessary amounts, thereby being involved in causing drug-resistant epilepsy. Although an invasive procedure, bypassing the BBB by targeted intracranial drug delivery is an attractive approach to circumvent BBB-associated drug resistance mechanisms and to lower the risk of systemic and neurologic adverse effects. Additionally, it offers the possibility of reaching higher local drug concentrations in appropriate target regions while minimizing them in other brain or peripheral areas, as well as using otherwise toxic drugs not suitable for systemic administration. In our review, we give an overview of experimental and clinical studies conducted on direct intracranial drug delivery in epilepsies. We also discuss challenges associated with intracranial pharmacotherapy for epilepsies.

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  • An intracerebral injection avoids the tissue barrier that the blood-CSF barrier or blood-brain-barrier represents and consequently should lead to significantly higher brain transfection levels by specifically targeting local regions of the brain.

    “An intracerebral injection avoids the tissue barrier that blood-cerebrospinal fluid (CSF) barrier or blood-brain-barrier (BBB) represents, and consequently should lead to significantly higher brain transfection levels by specifically targeting local regions of the brain (4, 20, 22, 26, 27).”

    From Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection (2023) · cites this paper as [22]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Intracerebral injections are clinically feasible and are performed in a variety of clinical scenarios and preclinical settings.

    “Intracerebral injections are clinically feasible, and are performed in a variety of clinical scenarios (17–23), as well as in various preclinical settings (4, 24–27).”

    From Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection (2023) · cites this paper as [22]

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Cited by

Sorted by citations

Authors
Gernert, M., & Feja, M.
Affiliations
University of Veterinary Medicine Hannover, Foundation (DE)
Corresponding author
Gernert, Manuela
ORCID
Venue
Pharmaceutics
Publisher
MDPI AG
Published
2020-11-24
Volume
12
Issue
12
Pages
1134
ISSN
1999-4923 (ISSN-L)
DOI
10.3390/pharmaceutics12121134
PMC
PMC7760299
OpenAlex
W3107993061
Cited by
68
References
2
Citations by year
2026: 11 · 2025: 10 · 2024: 10 · 2023: 15 · 2022: 14 · 2021: 8
FWCI
1.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Pharmaceutics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Deutsche Forschungsgemeinschaft (Ge 1103/9-1)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Keywords
epilepsy, blood-brain barrier, intracranial drug delivery, drug-resistant epilepsy, antiepileptic drugs, intracerebroventricular administration, intrathecal administration, adverse drug reactions, local drug concentration

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