Enhancing Intranasal Delivery and Bioavailability of Dihydroergotamine Utilizing Chitosan Nanoparticles

Abstract

Objective. Dihydroergotamine (DHE) is used for acute migraine treatment. Oral DHE is extensively metabolized; therefore, it must be given by a nonoral route. The aim of this study was to investigate the potential use of chitosan nanoparticles as a system for improving the systemic absorption of dihydroergotamine (DHE) following nasal administration. Methods. DHE-loaded chitosan nanoparticles (CS-NPs) were prepared by a modified ionotropic gelation method with sodium tripolyphosphate. The resulting nanoparticles were evaluated for size, drug loading, and in vitro release. DHE was administered at a dose of 0.5 mg/kg to male Sprague–Dawley rats intravenously, as an intranasal solution, or intranasal nanoparticles (n = 3 in each group). A special surgical procedure was performed to ensure that the drug solution was held in the nasal cavity. Blood samples were collected at appropriate times for 90 min. An HPLC-fluorescence detection method was employed to determine DHE in the plasma. Results. DHE chitosan nanoparticles with 20% loading had 95 ± 13% encapsulation efficiency and a particle size of 395 ± 59 nm. In vitro DHE release studies showed an initial burst followed by a slow release of DHE. DHE intranasal nanoparticles demonstrated significantly increased absolute bioavailability (82.5 ± 12.3%) over intranasal DHE solution administration (53.2 ± 7.7%). Conclusion. Taking in consideration the limitations of delivering DHE, the results of the present study demonstrate that DHE CS-NPs have a great potential for nasal DHE administration (55% increase in bioavailability) compared to intranasal solution with effective systemic absorption.