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Delivery of Brain-Derived Neurotrophic Factor via Nose-to-Brain Pathway

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ABSTRACT

Purpose

To investigate the plausibility of delivering brain-derived neurotrophic factor (BDNF) to brain via nose-to-brain pathway using chitosan as barrier-modulating agent.

Methods

Effect of different viscosity grades chitosan at different concentrations on permeation of fluorescein isothio-cyanate dextran (FD 40 K) across bovine olfactory mucosa was studied using Franz diffusion cells. Medium viscosity chitosan was used to carry out permeation studies of BDNF. Pharmacokinetic and pharmacodynamic studies were carried out in Sprague dawley rats upon intranasal/i.v administration of different formulations.

Results

Medium viscosity chitosan more efficiently enhanced permeation of FD 40 K across olfactory mucosa compared to other grades. In case of BDNF, medium viscosity chitosan (0.25% w/v) enhanced permeation ~14-fold over control (18.78 ± 16.69 ng/cm2). Brain bioavailability of rats administered intranasally with BDNF solution containing chitosan was significantly enhanced ~13-fold compared to rats administered with same concentration of BDNF solution without chitosan. In rats subjected to immobilization stress, BDNF solution containing chitosan significantly decreased immobility time.

Conclusions

Intranasal formulations containing chitosan as barrier-modulating agent significantly enhanced brain bioavailability of BDNF. Delivery of BDNF was found to counteract stress-induced depression in rats.

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ACKNOWLEDGMENTS & DISCLOSURES

The project was funded by Grant # 5P20RR021929 from the National Center for Research Resources (NCRR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. The authors would like to thank NCRR for funding the project.

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Authors and Affiliations

  1. Department of Pharmaceutics, The University of Mississippi School of Pharmacy, University, Mississippi, 38677, USA

    Siva Ram Kiran Vaka, Sathyanarayana Narasimha Murthy & Michael A. Repka

  2. The National Center for Natural Products Research, The University of Mississippi, University, Mississippi, 38677, USA

    Michael A. Repka

  3. Department of Pharmaceutics, Vaageswari College of Pharmacy, Karimnagar, AP, India

    Anna Balaji

  4. Department of Pharmaceutics, The University of Mississippi, 113 Faser Hall, University, Mississippi, 38677, USA

    Sathyanarayana Narasimha Murthy

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  1. Siva Ram Kiran Vaka
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  2. Sathyanarayana Narasimha Murthy
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  4. Michael A. Repka
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Correspondence to Sathyanarayana Narasimha Murthy.

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Vaka, S.R.K., Murthy, S.N., Balaji, A. et al. Delivery of Brain-Derived Neurotrophic Factor via Nose-to-Brain Pathway. Pharm Res 29, 441–447 (2012). https://doi.org/10.1007/s11095-011-0572-9

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  • DOI: https://doi.org/10.1007/s11095-011-0572-9

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