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<p>Migraine is a widespread neurological disorder, most common among adults aged 19–49, with a higher prevalence in women. While amitriptyline, a tricyclic antidepressant, is used preventively, its status as a first-line option remains controversial due to side effects and declining efficacy over time. This research developed an amitriptyline nano-formulation within a PVP polymer matrix to improve its stability, brain targeting, and therapeutic effect. The formulation provided rapid and controlled drug release. In migraine model mice, behavioural studies showed reduced photophobia and freezing. Biochemical assays indicated increases in lactic acid (<i>p</i> = 0.03) and glutamate (<i>p</i> = 0.04) during migraine, both reduced after treatment, highlighting the nano-formulation’s ability to mitigate glutamate excitotoxicity, even at low doses. Histopathology of the cortex and trigeminal nucleus caudalis revealed no cytotoxicity, confirming biocompatibility. This study suggests that nanocarrier-based delivery enhances amitriptyline’s pharmacokinetics, improving brain penetration and reducing systemic effects. This strategy may overcome limitations of the blood-brain barrier, offering safer, more effective migraine treatments. Further clinical investigation is warranted.</p>

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Amitriptyline-loaded polyvinyl pyrrolidone nano formulation for the management of nitroglycerin-induced migraine in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月4日

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  • Shraman Kumar Bohra,
  • Tafadzwa Justin Chiome,
  • Jérôme Laurin,
  • Christophe Pellegrino,
  • Vichitra Chandrasekaran,
  • Asha Srinivasan

摘要

Migraine is a widespread neurological disorder, most common among adults aged 19–49, with a higher prevalence in women. While amitriptyline, a tricyclic antidepressant, is used preventively, its status as a first-line option remains controversial due to side effects and declining efficacy over time. This research developed an amitriptyline nano-formulation within a PVP polymer matrix to improve its stability, brain targeting, and therapeutic effect. The formulation provided rapid and controlled drug release. In migraine model mice, behavioural studies showed reduced photophobia and freezing. Biochemical assays indicated increases in lactic acid (p = 0.03) and glutamate (p = 0.04) during migraine, both reduced after treatment, highlighting the nano-formulation’s ability to mitigate glutamate excitotoxicity, even at low doses. Histopathology of the cortex and trigeminal nucleus caudalis revealed no cytotoxicity, confirming biocompatibility. This study suggests that nanocarrier-based delivery enhances amitriptyline’s pharmacokinetics, improving brain penetration and reducing systemic effects. This strategy may overcome limitations of the blood-brain barrier, offering safer, more effective migraine treatments. Further clinical investigation is warranted.