Neuroprotective effect of ibuprofen by intranasal application of mucoadhesive nanoemulsion in MPTP induced Parkinson model

Abstract

This study was to investigate the neuroprotective effect of Ibuprofen by intranasal route against inflammation-mediated by dopaminergic neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model of Parkinson’s disease (PD). Ibuprofen loaded sodium hyaluronate based mucoadhesive nanoemulsion (MNEI) was developed by using response surface methodology (RSM) and was characterized. Male C57BL/6 mice were first treated with four intraperitoneal injections of MPTP (20 mg/kg of body weight) at 2 h intervals followed by Ibuprofen for 2 consecutive weeks at 2.86 mg/kg of body weight per day. Optimal MNEI containing 3 % Labrafil M 1944 CS as oil phase, 36 % of Accenon CC and Transcutol P at 3:1 ratio and 0.5 % sodium hyaluronate was stable, non-ciliotoxic with 46.3 ± 2.28 nm as average globule size PdI value and TEM result showed the narrow size distribution of MNEI. The result showed that all three independent variables had a significant effect (p < 0.05) on the responses. In-vivo results revealed significant reduction of MPTP-mediated dopamine depletion after nasal administration of Ibuprofen through MNEI. MPTP intoxication significantly decreased striatal DA content to 29.92 % which was elevated to 58.21 % after Ibuprofen treatment using MNEI. Significant improvement in motor performance and gross behavioural activity of the mice was observed through the findings of rota-rod and open field test findings. Findings of the investigation revealed that Ibuprofen through developed MNEI was shown to protect neurons against MPTP-induced injury in the striatum and could be a promising approach to treat PD.