Brain Targeted Delivery of Sumatriptan Succinate Loaded Chitosan Nanoparticles: Preparation, In Vitro Characterization, and (Neuro-)pharmacokinetic Evaluations

Abstract Migraine is a neurovascular disorder characterized by nausea, vomiting, pain, photophobia, phonophobia, and in some cases auras. Because of the complexity of the pathophysiology of migraine and the limited systemic availability of sumatriptan succinate after oral administration, oral delivery of sumatriptan succinate encountered with important limitations. During this study formulation and evaluation of the neuropharmacokinetics of intravenous and intranasal (IN)-administered sumatriptan succinate-loaded chitosan nanoparticles were considered. At first, formulation and characterization of drug-loaded chitosan nanoparticles were performed and then neuropharmacokinetic parameters including direct transport percentage (DTP) and drug targeting efficiency (DTE) were assessed by performing an in vivo study on rats. Ionic gelation technique led to the preparation of nanoparticles with 105 nm mean diameter and polydispersity index (PDI) of 0.38. The drug entrapment efficiency (EE) for the nanoparticles was calculated 59.60±2.12%. In vitro release study indicated that 12 and 32% of the drug were released in the first 1 and 4 hours after the beginning of the experiment. DTE and DTP of IN-administered nanoparticles were calculated 493.39% and 79.79%, respectively. Neuropharmacokinetic evaluations of the polymeric nanoparticles represent a suitable brain delivery system. The high DTP value for nanoparticles confirms the satisfactory entrance of the drug into the higher parts of the brain.