title: Intracranial biodegradable silica-based nimodipine drug release implant for treating vasospasm in subarachnoid hemorrhage in an experimental healthy pig and dog model.
abstract: 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.
authors: Faculty of Medicine, University of Turku, P.O. Box 52, Kiinamyllynkatu 4-8, 20520 Turku, Finland ; Department of Neurosurgery, Helsinki University Central Hospital, P.O. Box 266, Topeliuksenkatu 5, 00029 Helsinki, Finland.
authors: Janne
authors: J
authors: Koskimäki
authors: Turku PET Centre, University of Turku and Turku University Hospital, P.O. Box 52, Kiinamyllynkatu 4-8, 20521 Turku, Finland.
authors: Miikka
authors: M
authors: Tarkia
authors: Chemistry and Safety Sciences, R&D, Orion Corporation, Orion Pharma, P.O. Box 65, Orionintie 1A, 02101 Espoo, Finland.
authors: Tuula
authors: T
authors: Ahtola-Sätilä
authors: Chemistry and Safety Sciences, R&D, Orion Corporation, Orion Pharma, P.O. Box 65, Orionintie 1A, 02101 Espoo, Finland.
authors: Lasse
authors: L
authors: Saloranta
authors: Chemistry and Safety Sciences, R&D, Orion Corporation, Orion Pharma, P.O. Box 65, Orionintie 1A, 02101 Espoo, Finland.
authors: Outi
authors: 0000-0003-2698-2076
authors: O
authors: Simola
authors: Delsitech Ltd., Itäinen Pitkäkatu 4B, 20520 Turku, Finland.
authors: Ari-Pekka
authors: 0000-0002-9108-665X
authors: AP
authors: Forsback
authors: Department of Neurosurgery, Helsinki University Central Hospital, P.O. Box 266, Topeliuksenkatu 5, 00029 Helsinki, Finland.
authors: Aki
authors: A
authors: Laakso
authors: Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital, P.O. Box 52, Hämeentie 11, 20521 Turku, Finland.
authors: Janek
authors: J
authors: Frantzén
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics / Q000494:pharmacology; D004195:Disease Models, Animal; D004285:Dogs; D002532:Intracranial Aneurysm / Q000601:surgery; D009553:Nimodipine / Q000493:pharmacokinetics / Q000494:pharmacology; D012822:Silicon Dioxide / Q000493:pharmacokinetics / Q000494:pharmacology; D013345:Subarachnoid Hemorrhage / Q000517:prevention & control*; D013552:Swine; D014665:Vasodilator Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D020301:Vasospasm, Intracranial / Q000517:prevention & control*
chemical_list: D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; D009553:Nimodipine; D012822:Silicon Dioxide