Intracranial Biodegradable Silica-Based Nimodipine Drug Release Implant for Treating Vasospasm in Subarachnoid Hemorrhage in an Experimental Healthy Pig and Dog Model
Nimodipine is a widely used medication for treating delayed cerebral ischemia (DCI) after subarachnoid hemorrhage. When administrated orally or intravenously, systemic hypotension is an undesirable side effect. Intracranial subarachnoid delivery of nimodipine during aneurysm clipping may be more eff...
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doaj-84f7ef2cc9ac445c9638204d1a00e3602020-11-24T22:17:45ZengHindawi LimitedBioMed Research International2314-61332314-61412015-01-01201510.1155/2015/715752715752Intracranial Biodegradable Silica-Based Nimodipine Drug Release Implant for Treating Vasospasm in Subarachnoid Hemorrhage in an Experimental Healthy Pig and Dog ModelJanne Koskimäki0Miikka Tarkia1Tuula Ahtola-Sätilä2Lasse Saloranta3Outi Simola4Ari-Pekka Forsback5Aki Laakso6Janek Frantzén7Faculty of Medicine, University of Turku, P.O. Box 52, Kiinamyllynkatu 4-8, 20520 Turku, FinlandTurku PET Centre, University of Turku and Turku University Hospital, P.O. Box 52, Kiinamyllynkatu 4-8, 20521 Turku, FinlandChemistry and Safety Sciences, R&D, Orion Corporation, Orion Pharma, P.O. Box 65, Orionintie 1A, 02101 Espoo, FinlandChemistry and Safety Sciences, R&D, Orion Corporation, Orion Pharma, P.O. Box 65, Orionintie 1A, 02101 Espoo, FinlandChemistry and Safety Sciences, R&D, Orion Corporation, Orion Pharma, P.O. Box 65, Orionintie 1A, 02101 Espoo, FinlandDelsitech Ltd., Itäinen Pitkäkatu 4B, 20520 Turku, FinlandDepartment of Neurosurgery, Helsinki University Central Hospital, P.O. Box 266, Topeliuksenkatu 5, 00029 Helsinki, FinlandClinical Neurosciences, Department of Neurosurgery, Turku University Hospital, P.O. Box 52, Hämeentie 11, 20521 Turku, FinlandNimodipine is a widely used medication for treating delayed cerebral ischemia (DCI) after subarachnoid hemorrhage. When administrated orally or intravenously, systemic hypotension is an undesirable side effect. Intracranial subarachnoid delivery of nimodipine during aneurysm clipping may be more efficient way of preventing vasospasm and DCI due to higher concentration of nimodipine in cerebrospinal fluid (CSF). The risk of systemic hypotension may also be decreased with intracranial delivery. We used animal models to evaluate the feasibility of surgically implanting a silica-based nimodipine releasing implant into the subarachnoid space through a frontotemporal craniotomy. Concentrations of released nimodipine were measured from plasma samples and CSF samples. Implant degradation was followed using CT imaging. After completing the recovery period, full histological examination was performed on the brain and meninges. The in vitro characteristics of the implant were determined. Our results show that the biodegradable silica-based implant can be used for an intracranial drug delivery system and no major histopathological foreign body reactions were observed. CT imaging is a feasible method for determining the degradation of silica implants in vivo. The sustained release profiles of nimodipine in CSF were achieved. Compared to a traditional treatment, higher nimodipine CSF/plasma ratios can be obtained with the implant.http://dx.doi.org/10.1155/2015/715752 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Janne Koskimäki Miikka Tarkia Tuula Ahtola-Sätilä Lasse Saloranta Outi Simola Ari-Pekka Forsback Aki Laakso Janek Frantzén |
spellingShingle |
Janne Koskimäki Miikka Tarkia Tuula Ahtola-Sätilä Lasse Saloranta Outi Simola Ari-Pekka Forsback Aki Laakso Janek Frantzén Intracranial Biodegradable Silica-Based Nimodipine Drug Release Implant for Treating Vasospasm in Subarachnoid Hemorrhage in an Experimental Healthy Pig and Dog Model BioMed Research International |
author_facet |
Janne Koskimäki Miikka Tarkia Tuula Ahtola-Sätilä Lasse Saloranta Outi Simola Ari-Pekka Forsback Aki Laakso Janek Frantzén |
author_sort |
Janne Koskimäki |
title |
Intracranial Biodegradable Silica-Based Nimodipine Drug Release Implant for Treating Vasospasm in Subarachnoid Hemorrhage in an Experimental Healthy Pig and Dog Model |
title_short |
Intracranial Biodegradable Silica-Based Nimodipine Drug Release Implant for Treating Vasospasm in Subarachnoid Hemorrhage in an Experimental Healthy Pig and Dog Model |
title_full |
Intracranial Biodegradable Silica-Based Nimodipine Drug Release Implant for Treating Vasospasm in Subarachnoid Hemorrhage in an Experimental Healthy Pig and Dog Model |
title_fullStr |
Intracranial Biodegradable Silica-Based Nimodipine Drug Release Implant for Treating Vasospasm in Subarachnoid Hemorrhage in an Experimental Healthy Pig and Dog Model |
title_full_unstemmed |
Intracranial Biodegradable Silica-Based Nimodipine Drug Release Implant for Treating Vasospasm in Subarachnoid Hemorrhage in an Experimental Healthy Pig and Dog Model |
title_sort |
intracranial biodegradable silica-based nimodipine drug release implant for treating vasospasm in subarachnoid hemorrhage in an experimental healthy pig and dog model |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2015-01-01 |
description |
Nimodipine is a widely used medication for treating delayed cerebral ischemia (DCI) after subarachnoid hemorrhage. When administrated orally or intravenously, systemic hypotension is an undesirable side effect. Intracranial subarachnoid delivery of nimodipine during aneurysm clipping may be more efficient way of preventing vasospasm and DCI due to higher concentration of nimodipine in cerebrospinal fluid (CSF). The risk of systemic hypotension may also be decreased with intracranial delivery. We used animal models to evaluate the feasibility of surgically implanting a silica-based nimodipine releasing implant into the subarachnoid space through a frontotemporal craniotomy. Concentrations of released nimodipine were measured from plasma samples and CSF samples. Implant degradation was followed using CT imaging. After completing the recovery period, full histological examination was performed on the brain and meninges. The in vitro characteristics of the implant were determined. Our results show that the biodegradable silica-based implant can be used for an intracranial drug delivery system and no major histopathological foreign body reactions were observed. CT imaging is a feasible method for determining the degradation of silica implants in vivo. The sustained release profiles of nimodipine in CSF were achieved. Compared to a traditional treatment, higher nimodipine CSF/plasma ratios can be obtained with the implant. |
url |
http://dx.doi.org/10.1155/2015/715752 |
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