Pharmacokinetic study and brain tissue analysis of Zolmitriptan loaded chitosan nanoparticles in rats by LC-MS method

Introduction: Migraine has recently become a major interest to the neuroscientists. Zolmitriptan is an effective medicine used in the treatment of migraine. The nasal spray was prepared from Zolmitriptan loaded chitosan nanoparticles and evaluated for pharmacokinetic properties. Methods: In this study male Wistar albino rats weighing between 200 and 250 g were taken and divided into 4 groups with 6 rats in each group. Nasal spray containing Zolmitriptan loaded Chitosan nanoparticles were administered nasally (using specific inhalation mask) at a dose of 0.5 mg/kg as a test formulation and compared with the control groups which received either water for injection or marketed standard drug (Zolmist) or standard drug solution at a same dose. The pharmacokinetic parameters such as C-max, T-max and brain tissue analyses for accumulation of drug were performed for Zolmitriptan by LC-MS method. Results: Amount of drug in the plasma from the test formulation, standard marketed drug (Zolmist) and standard drug solution was found to be 41.37 +/- 2.31, 34.76 +/- 4.22 and 23.74 +/- 2.42 ng/ml at 10 min respectively, which indicated significantly (p < 0.05) greater amount of drug being delivered from the test formulation compared to the both standard groups. The amount of the drug (Zolmitriptan) present in brain tissue (Olfactory lobe) was found to be 15 +/- 0.08, 13 +/- 0.14 and 8 +/- 0.13 ng/g at 60 min for test formulation, marketed standard and standard drug solution respectively which indicates significantly (p < 0.05) higher amount of drug absorption in brain tissue from the test formulation compared to both the standard groups. Conclusion: Pharmacokinetics studies of nasal spray containing Zolmitriptan loaded chitosan nanoparticles proved rapid onset of action in animals and is promising in treatment of migraine. (C) 2019 Elsevier B.V. All rights reserved.