Bypassing the Blood–Brain Barrier: Direct Intracranial Drug Delivery in Epilepsies
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 ma...
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| Format: | Article |
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MDPI AG
2020-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/12/1134 |
| _version_ | 1797546890334568448 |
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| author | Manuela Gernert Malte Feja |
| author_facet | Manuela Gernert Malte Feja |
| author_sort | Manuela Gernert |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T14:35:41Z |
| format | Article |
| id | doaj.art-2f73ebe8c26e4d9590eb96f41b3432fa |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T14:35:41Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-2f73ebe8c26e4d9590eb96f41b3432fa2023-11-20T22:09:39ZengMDPI AGPharmaceutics1999-49232020-11-011212113410.3390/pharmaceutics12121134Bypassing the Blood–Brain Barrier: Direct Intracranial Drug Delivery in EpilepsiesManuela Gernert0Malte Feja1Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, GermanyDepartment of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, GermanyEpilepsies 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.https://www.mdpi.com/1999-4923/12/12/1134drug-resistant epilepsyseizuresfocal epilepsytemporal lobe epilepsyintracerebral drug deliverytargeted drug delivery |
| spellingShingle | Manuela Gernert Malte Feja Bypassing the Blood–Brain Barrier: Direct Intracranial Drug Delivery in Epilepsies Pharmaceutics drug-resistant epilepsy seizures focal epilepsy temporal lobe epilepsy intracerebral drug delivery targeted drug delivery |
| title | Bypassing the Blood–Brain Barrier: Direct Intracranial Drug Delivery in Epilepsies |
| title_full | Bypassing the Blood–Brain Barrier: Direct Intracranial Drug Delivery in Epilepsies |
| title_fullStr | Bypassing the Blood–Brain Barrier: Direct Intracranial Drug Delivery in Epilepsies |
| title_full_unstemmed | Bypassing the Blood–Brain Barrier: Direct Intracranial Drug Delivery in Epilepsies |
| title_short | Bypassing the Blood–Brain Barrier: Direct Intracranial Drug Delivery in Epilepsies |
| title_sort | bypassing the blood brain barrier direct intracranial drug delivery in epilepsies |
| topic | drug-resistant epilepsy seizures focal epilepsy temporal lobe epilepsy intracerebral drug delivery targeted drug delivery |
| url | https://www.mdpi.com/1999-4923/12/12/1134 |
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