Preparation and Evaluation of Nanostructured Lipid Carrier-Based Hydrogel for Intranasal Administration of Lorazepam for Treatment of Status Epilepticus

Background: Status epilepticus is defined as a condition in which epileptic seizures lasts more than 5 minutes and must be treated aggressively because of the brain damage risk. The benzodiazepine of choice for initial treatment is lorazepam (LZM). Nasal drug delivery is a non-invasive route of administration for direct nose-to-brain delivery without passing the blood–brain barrier. It delivers the drugs to brain without systemic absorption, thus avoiding the side effects and enhancing the efficacy of neurotherapeutics. The use of nanoparticles for nasal drug delivery cause quick absorption, controlled drug release and enhance residence time in nasal cavity especially if nanoparticles load in a gelling system. In this study, chitosan-thermosensitive hydrogel containing LZM nanostructured lipid carriers (NLC) was prepared and used in pentylenetetrazole (PTZ) induced seizures’ rats to evaluate its in vivo performance. Methods: LZM-NLCs were prepared by emulsification solvent diffusion and evaporation method. The effects of differents factors like lipid/drug ratio, oil content and surfactant concentration were investigated by using Design Expert software (version10, USA). Furthermore, chitosan/β-Glycerophosphate in situ hydrogel containing LZM-NLCs (LZM-NLCs-Gel) were prepared and performance of the optimal formulation was investigated in four groups of PTZ-induced seizures’ rats. Findings:The mean particle size of the LZM-NLCs was found to be71.7±5.2nm with PdI of 0.21±0.23 and negative zeta potential (-20/06±2/70mV). The drug entrapment efficiency of NLCs was 81.80±5.04. In situ hydrogel containing LZM-NLCs were prepared by chitosan (%2 w/v) and β-glycerophosphate (%15w/v). LZM-NLCs-Gel could reduce prevalence of epileptic seizure, duration of symptoms, severity of symptom and increase time of incidence in rats.Conclusion: Hydrogel containing LZM-NLCs is a novel drug delivery system for delivery of LZM through nose to brain. The system showed to be effective to prevent and treat status epilepticus in rats.

کلیدواژه ها:

Status epilepticus ، Nasal drug delivery ، Insitu gelling system ، Lorazepam ، pentylenetetrazole