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Micellar Nanocarriers: Potential Nose-to-Brain Delivery of Zolmitriptan as Novel Migraine Therapy

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Abstract

Purpose

The investigation was aimed at developing micellar nanocarriers for nose-to-brain delivery of zolmitriptan with the objective to investigate the pathway involved in the drug transport.

Methods

The micellar nanocarrier was successfully formulated and characterized for particle size and shape by multi-angle dynamic light scattering, small angle neutron scattering and cryo-transmission electron microscopy. Toxicity and biodistribution studies were carried out in rat. The distribution of the nasally administered labeled micellar nanocarrier in various regions of the rat brain was determined using the brain localization and autoradiography studies.

Results

Micellar nanocarrier of zolmitriptan, with size of around 23 nm, was successfully formulated. The spherical nature of the nanocarrier was confirmed using DLS, SANS and cryo-TEM. Toxicity studies indicated the safety for administration in the nasal cavity. In vivo biodistribution studies indicated the superiority of the developed nanocarrier for brain targeting when compared with the intravenous and nasal solutions of the drug. Brain localization and autoradiography studies illustrated the distribution of the drug in various regions of the brain and revealed a possible nose-to-brain transport pathway for the labeled drug.

Conclusion

The investigation indicated the potential of the developed nanocarrier as an effective new-generation vehicle for brain targeting of zolmitriptan.

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Acknowledgements

The authors are thankful to Archarchem Pharmaceuticals Pvt. Ltd. and Chokhani Pharmaceutical Ltd. for the gift sample of zolmitriptan; Gattefosse, Mumbai, India and BASF India Ltd. for the gift sample of excipients; and Aptar Pharma India Pvt. Ltd., Mumbai, India for the kind gift of Equadel™ Pump. The authors are grateful to Lalit Borde and Dr. Krishanu Ray from Tata Institute of Fundamental Research, Mumbai, India; Prof. Katarina Edwards, Uppsala University, Uppsala, Sweden; and Prof. Ishi Talmon, Haifa, Israel for conducting the cryo-TEM analysis. The authors are thankful to Dr. P. A. Hassan, Dr. V. K. Aswal for DLS and SANS analysis, and Dr. Tanuja Shet for authoradiography Studies. Ratnesh Jain is thankful to the Board of Research in Nuclear Sciences (Sanction No. 2006/35/11/BRNS), Department of Atomic Energy, Gov’t of India, for providing the funding to execute the research.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai, 400 019, India

    Ratnesh Jain, Prajakta Dandekar & Vandana Patravale

  2. Radiation Medicine Centre, Bhabha Atomic Research Centre, Parel, Mumbai, 400 012, India

    Swapna Nabar

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  1. Ratnesh Jain
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  2. Swapna Nabar
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  3. Prajakta Dandekar
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  4. Vandana Patravale
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Correspondence to Vandana Patravale.

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Jain, R., Nabar, S., Dandekar, P. et al. Micellar Nanocarriers: Potential Nose-to-Brain Delivery of Zolmitriptan as Novel Migraine Therapy. Pharm Res 27, 655–664 (2010). https://doi.org/10.1007/s11095-009-0041-x

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  • DOI: https://doi.org/10.1007/s11095-009-0041-x

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