Bypassing the Blood–Brain Barrier: Direct Intracranial Drug Delivery in Epilepsies
Abstract
:1. Introduction
2. Technical Considerations
3. Animal Model Aspects
4. Targeting the Seizure Focus
4.1. Intracerebroventricular (Icv) Drug Delivery to Modulate Seizure Focus
4.1.1. Acute Icv Drug Delivery in Animal Models of Seizures/Epilepsies
4.1.2. Chronic Icv Drug Delivery in Animal Models of Seizures/Epilepsies
4.1.3. Icv Drug Delivery in Humans with Drug-Resistant Epilepsy (DRE)
4.2. Transmeningeal Drug Delivery to Modulate Seizure Focus
4.2.1. Acute Transmeningeal Drug Delivery in Animal Models of Seizures/Epilepsies
4.2.2. Chronic Transmeningeal Drug Delivery in Animal Models of Seizures/Epilepsies
4.2.3. Transmeningeal Drug Delivery in Humans with DRE
4.3. Intraparenchymal Drug Delivery to Modulate Seizure Focus
4.3.1. Acute Intraparenchymal Drug Delivery in Animal Models of Seizures/Epilepsies
4.3.2. Chronic Intraparenchymal Drug Delivery in Animal Models of Seizures/Epilepsies
4.3.3. Intraparenchymal Drug Delivery in Humans with DRE
5. Targeting Remote Brain Structures of the Epileptic Network
5.1. Basal Ganglia
5.1.1. Basal Ganglia Anatomical and Pathophysiological Background
5.1.2. Acute Basal Ganglia Drug Delivery in Animal Models of Seizures/Epilepsies
5.1.3. Chronic Basal Ganglia Drug Delivery in Animal Models of Seizures/Epilepsies
5.1.4. Lack of Clinical Trials of Drug Delivery into Basal Ganglia in Humans with DRE
5.2. Thalamic Regions
5.3. Further Regions
6. Challenges
6.1. Drug Resistance
6.2. Pharmacological Tolerance upon Intracranial Drug Delivery
6.3. Differences in Brain Size and Connectivity between Laboratory Animals and Humans
7. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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Gernert, M.; Feja, M. Bypassing the Blood–Brain Barrier: Direct Intracranial Drug Delivery in Epilepsies. Pharmaceutics 2020, 12, 1134. https://doi.org/10.3390/pharmaceutics12121134
Gernert M, Feja M. Bypassing the Blood–Brain Barrier: Direct Intracranial Drug Delivery in Epilepsies. Pharmaceutics. 2020; 12(12):1134. https://doi.org/10.3390/pharmaceutics12121134
Chicago/Turabian StyleGernert, Manuela, and Malte Feja. 2020. "Bypassing the Blood–Brain Barrier: Direct Intracranial Drug Delivery in Epilepsies" Pharmaceutics 12, no. 12: 1134. https://doi.org/10.3390/pharmaceutics12121134