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BioMed Research International
Volume 2015, Article ID 715752, 10 pages
http://dx.doi.org/10.1155/2015/715752
Research Article

Intracranial Biodegradable Silica-Based Nimodipine Drug Release Implant for Treating Vasospasm in Subarachnoid Hemorrhage in an Experimental Healthy Pig and Dog Model

1Faculty of Medicine, University of Turku, P.O. Box 52, Kiinamyllynkatu 4-8, 20520 Turku, Finland
2Department of Neurosurgery, Helsinki University Central Hospital, P.O. Box 266, Topeliuksenkatu 5, 00029 Helsinki, Finland
3Turku PET Centre, University of Turku and Turku University Hospital, P.O. Box 52, Kiinamyllynkatu 4-8, 20521 Turku, Finland
4Chemistry and Safety Sciences, R&D, Orion Corporation, Orion Pharma, P.O. Box 65, Orionintie 1A, 02101 Espoo, Finland
5Delsitech Ltd., Itäinen Pitkäkatu 4B, 20520 Turku, Finland
6Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital, P.O. Box 52, Hämeentie 11, 20521 Turku, Finland

Received 26 August 2014; Accepted 10 October 2014

Academic Editor: Kuo-Sheng Hung

Copyright © 2015 Janne Koskimäki et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.