Background: The present study is to investigate the neuroprotective effect of ibuprofen by intranasal administration of mucoadhesive microemulsion (MMEI) against inflammation-mediated by dopaminergic neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease (PD).
Methods: Ibuprofen-loaded polycarbophil-based MMEI was developed by using response surface methodology (RSM). Ibuprofen with dose of 2.86 mg/kg/day was administered intranasally to male C57BL/6 mice for two consecutive weeks which were pre-treated with four intraperitoneal injections of MPTP (20 mg/kg of body weight) at 2 h intervals. Immunohistochemistry was performed.
Results: Optimal MMEI was stable and non-ciliotoxic with 66.29 ± 4.15 nm as average globule size and -20.9 ± 3.98 mV as zeta potential. PDI value and transmission electron microscopy result showed the narrow globule size distribution of MMEI. The result showed that all three independent variables had a significant effect (p < 0.05) on the responses. Rota-rod and open-field test findings revealed the significant improvement in motor performance and gross behavioral activity of the mice. The results from in vivo study and immunohistochemistry showed that nasal administration of Ibuprofen significantly reduced the MPTP-mediated dopamine depletion. Furthermore TH neurons count in the substantia nigra and the density of striatal dopaminergic nerve terminals were found to be significant higher for ibuprofen treated groups.
Conclusion: Findings of the investigation revealed that Ibuprofen through developed MMEI was shown to protect neurons against MPTP-induced injury in the Substantia nigra pars compacta (SNpc) and striatum and hence, could be a promising approach for brain targeting of Ibuprofen through intranasal route to treat PD.
Keywords: Box–Behnken design; Capmul MCM; flux; male C57BL/6 mice; response surface methodology (RSM).