Amitriptyline-Loaded Polyvinyl Pyrrolidone Nano Formulation For The Management Of Nitroglycerin-Induced Migraine In Mice

Abstract Migraine is a globally prevalent neurological disorder affecting mostly individuals within the 19–49 age group, while being more prevalent in women. Amitriptyline, a tricyclic antidepressant, is used as a prophylactic treatment. However, its first-line use remains controversial due to side effects and reduced efficacy over time. This study focused on developing a nano-formulation of amitriptyline encapsulated in a PVP polymer matrix to enhance its stability, brain uptake, and therapeutic efficacy. The resulting formulation exhibited controlled drug release with an early onset.Behavioural studies in nitroglycerin-induced migraine mice demonstrated a significant reduction in photophobia and freezing behaviour. Biochemical analysis confirmed migraine onset through increased lactic acid and glutamate levels, which decreased post-treatment, indicating the nano-formulation’s effectiveness in mitigating glutamate excitotoxicity even at low doses. Histopathological examination of the cortex and trigeminal nucleus caudalis showed no signs of cytotoxic damage, demonstrating the formulation’s biocompatibility. These findings highlight the potential of nano-based drug delivery systems to improve amitriptyline’s pharmacokinetics, ensuring better brain penetration while minimizing systemic side effects. Overcoming the challenges posed by the blood-brain barrier, this approach could lead to safer and more effective treatments for migraine. Further research is required to translate these findings into clinical applications.