Targeted antimigraine therapy using lactoferrin conjugated liposomal magnesium sulfate: in vivo safety and efficacy studies

Migraine is a neurovascular disorder characterized by recurrent headaches and sensitivity to light, sound and movement. Magnesium has therapeutic potential in migraine, but poor brain bioavailability may limit its efficacy. This study evaluated lactoferrin conjugated liposome loaded with magnesium sulfate (LMGPLS) as a targeted brain delivery system. Acute toxicity was assessed in male and female rats with graded doses of LMGPLS. Haematological and biochemical findings of LMGPLS showed no observable toxicity up to 200 mg/kg of magnesium sulfate. Antimigraine activity was evaluated in a nitroglycerin-induced rat model (10 mg/kg, s.c.) using behavioral, biomarker, magnesium distribution and histopathological analyses. LMGPLS (100 mg/kg) improved locomotor activity and reduced anxiety-like behavior compared with migraine-induced controls. It also reduced glutamate, nNOS, CGRP, and substance P while increasing magnesium in brain tissue and cerebrospinal fluid, with minimal plasma change. These findings support enhanced brain delivery of magnesium by LMGPLS and an antimigraine effect associated with modulation of glutamate, nNOS, and vasoactive neuropeptides.