Enhancing Intranasal Delivery and Bioavailability of Dihydroergotamine Utilizing Chitosan Nanoparticles
Ahmed Alastal, Amani D. Abu Kwaik, Azzam A. Malkawi, Sarah Baltzley, Abeer M. Al-Ghananeem
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.