Development of Midazolam Loaded Poly(D, L-lactide-co-glycolic acid) Nanoparticles for Treatment of Status Epilepticus

摘要

Midazolam is used as a first line drug for the treatment of status epilepticus. The highly lipophilic nature provides rapid onset action but only for short duration of time. The present study is aimed to develop PLGA nanoparticles loaded with midazolam to achieve controlled release and brain targeting action in treatment of status epilepticus. The NPs were formulated by nanoprecipitation method and optimized using Response Surface Methodology (RSM). Three factors, two levels Box-Behnken design was used keeping polymer, poloxamer, w/o phase ratio as independent factors and z-average, % drug entrapment as response. Developed NPs were characterized for z-average, zeta potential and % drug entrapment. Surface morphology of optimized NPs formulation was investigated using Transmission Electron Microscopy (TEM). Developed NPs showed z-average and % drug entrapment in the range of 116-261 d.nm and 71-88% respectively with PDI below 0.25 and zeta potential within the range of -28 mV. The study demonstrated that stable midazolam NPs were successfully developed and can be used for potential delivery of midazolam to the brain.