title: In situ forming nimodipine depot system based on microparticles for the treatment of posthemorrhagic cerebral vasospasm.
abstract: The present study was conducted to examine the feasibility of nimodipine-loaded PLGA microparticles suspended in Tisseel fibrin sealant as an in situ forming depot system. This device locally placed can be used for the treatment of vasospasm after a subarachnoid hemorrhage. Microparticles were prepared via spray-drying by using the vibration mesh spray technology of Nano Spray Dryer B-90. Spherically shaped microparticles with different loadings and high encapsulation efficiencies of 93.3-97.8% were obtained. Depending on nimodipine loading (10-40%), the particle diameter ranged from 1.9 ± 1.2 μm to 2.4 ± 1.3 μm. Thermal analyses using DSC revealed that nimodipine is dissolved in the PLGA matrix. Also, fluorescent dye loaded microparticles were encapsulated in Tisseel to examine the homogeneity of particles. 3D-pictures of the in situ forming devices displayed uniform particle homogeneity in the sealant matrix. Drug release was examined by fluorescence spectrophotometry which demonstrated a drug release proportional to the square root of time. A prolonged drug release of 19.5h was demonstrated under in vitro conditions. Overall, the nimodipine in situ forming device could be a promising candidate for the local treatment of vasospasm after a subarachnoid hemorrhage.
authors.affiliation: Department of Pharmaceutics and Biopharmacy, Philipps-Universität, Marburg, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Bege
authors.forename: Thomas
authors.initials: T
authors.lastname: Renette
authors.forename: Thomas
authors.initials: T
authors.lastname: Endres
authors.forename: Moritz
authors.initials: M
authors.lastname: Beck-Broichsitter
authors.forename: Daniel
authors.initials: D
authors.lastname: Hänggi
authors.forename: Thomas
authors.initials: T
authors.lastname: Kissel
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D008863:Microspheres; D009553:Nimodipine / Q000737:chemistry* / Q000493:pharmacokinetics; D013345:Subarachnoid Hemorrhage; D016896:Treatment Outcome; D020301:Vasospasm, Intracranial
chemical_list: D003692:Delayed-Action Preparations; D009553:Nimodipine