Electrospun Nimodipine-loaded fibers for nerve regeneration: Development and in vitro performance

Nimodipine is a 1,4-Dihydropyridine type calcium antagonist routinely used to control blood pressure and reduce the risk of secondary ischemia after aneurismal subarachnoid hemorrhage. Additionally, Nimodipine has unique neuroprotective properties. With respect to brain related applications, the full potential of the desired local effect can often not be realized after systemic administration due to systemic side effects. Therefore, it was our aim to develop a biodegradable drug delivery system for the local controlled release of the drug inside the brain. As a suitable and biodegradable system we successfully electrospun PLGA fibers containing 1 and 10% drug. The results of DSC and X-Ray diffractometry measurements indicate that Nimodipine was incorporated in the polymer matrix in the amorphous state. No drug recrystallization was detected for up to 6 months. Electron-beam sterilization was tried but reduced the drug content of the fiber mats considerably. A sustained drug release over 4-8 days was observed, highly depended on release conditions. The Nimodipine fiber mats exhibited no cell toxicity. In contrast, the electrospun fibers were able to significantly reduce cell death in in vitro cell models of oxidative, osmotic and heat-induced cell stress in Schwann cells, neuronal cells as well as immortalized and primary astrocytes. Therefore, electrospun Nimodipine loaded PLGA fibers represent a promising drug delivery system to realize the druǵs benefits for its intracranial use.