In situ forming nimodipine depot system based on microparticles for the treatment of posthemorrhagic cerebral vasospasm

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 19.5 h 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.

The feasibility to incorporate nimodipine-loaded PLGA microparticles into fibrin sealant was shown. Microparticles with different loadings (10–40%) were produced via spray-drying. The particles were homogeneously arranged in the fibrin sealant matrix. A prolonged drug release of 19.5 h was demonstrated, so the nimodipin in situ forming device is a promising candidate for the treatment of vasospasm after subarachnoid hemorrhage.Figure optionsDownload high-quality image (229 K)Download as PowerPoint slide