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KMID : 0369820160460010041
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Jorunal of Korean Pharmaceutical Sciences
2016 Volume.46 No. 1 p.41 ~ p.53
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Neuroprotective effect of ibuprofen by intranasal application of mucoadhesive nanoemulsion in MPTP induced Parkinson model
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Mandal Surjyanarayan
Mandal Snigdha Das
Chuttani Krishna
Sawant Krutika K.
Subudhi Bharat Bhushan
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Abstract
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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.
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KEYWORD
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Response surface methodology (RSM), Box-Behnken design, Flux, Sodium hyaluronate, Male C57BL/6 mice
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