Anticonvulsant and Acute Toxicity Evaluation of Phenytoin Sodium–loaded Polymeric Nanomicelle in MES Rat Model

An acute seizure is a medical condition which, if untreated, can lead to brain damage and even death. Phenytoin sodium is a second-line drug of choice for seizure emergencies. Due to the administration issues as well as pharmacokinetic issues of the drug, it is now being replaced with newer anticonvulsant drugs despite short half life and sedative effects. This study aims to develop a polymeric nanomicelle of phenytoin sodium that decreases administration difficulties, enhances drug availability in the brain, and lowers the dose, all of which could be advantageous in the treatment of seizure emergencies. Phenytoin sodium–loaded polymeric nanomicelle was prepared by thin-film hydration method. A novel polymeric nanomicelle of size less than 20 nm loaded with phenytoin sodium was prepared with pluronic F127. Drug-loaded polymeric nanomicelle showed an immediate release profile with reduced PPB and improved lipid permeation when compared with the marketed iv injection of Phenytoin sodium. The in vivo acute toxicity study results revealed that the optimized formulation is safe for administration. The pharmacodynamic study by the MES model proved the enhanced brain availability as well as the reduced dose, thereby reducing peripheral toxicity. Results from the above studies confirm that the phenytoin sodium–loaded polymeric nanomicelle could potentially to be a better candidate for seizure emergencies, as it could reduce the administration issues, improve the brain availability of phenytoin, and lower the dose requirements.