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

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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.

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Acknowledgments

All authors (S. Mandal, S. D. Mandal, K. Chuttani, K. K. Sawant, B. B. Subudhi) declare that they have no conflict of interest. All authors would like to thanks Abbott pharmaceutical Ltd. (Goa, India) for providing Ibuprofen as gift sample. The authors thank Abitec Corporation, Jackson St Janesville, USA and Gattefosse, France for gifting oils, surfactants and co-surfactants. The authors are thankful to Institute of Nuclear Medicine and Allied Sciences, Ministry of Defense, New Delhi, India for providing Male C57BL/6 mice. The authors are also grateful to Mrs. Kavitha Pillai for proof-reading the manuscript for grammatical and spelling errors.

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Siksha ‘O’ Anusandhan University, Khandagiri Square, Bhubaneswar, Orissa, India

    Surjyanarayan Mandal & Bharat Bhushan Subudhi

  2. Department of Pharmacology, Parul Institute of Pharmacy and Research, Vadodara, Gujarat, India

    Snigdha Das Mandal

  3. Division of Cyclotron & Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Delhi, 110054, India

    Krishna Chuttani

  4. Department of Pharmaceutics, MS University,TIFAC Core, Vadodara, India

    Krutika K. Sawant

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  1. Surjyanarayan Mandal
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  2. Snigdha Das Mandal
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  3. Krishna Chuttani
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  4. Krutika K. Sawant
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  5. Bharat Bhushan Subudhi
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Correspondence to Surjyanarayan Mandal.

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Mandal, S., Das Mandal, S., Chuttani, K. et al. Neuroprotective effect of ibuprofen by intranasal application of mucoadhesive nanoemulsion in MPTP induced Parkinson model. Journal of Pharmaceutical Investigation 46, 41–53 (2016). https://doi.org/10.1007/s40005-015-0212-1

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  • DOI: https://doi.org/10.1007/s40005-015-0212-1

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