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Nanoformulations of Antiepileptic Drugs: In Vitro and In Vivo Studies

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Antiepileptic Drug Discovery

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Epilepsy is a chronic neurological disorder that represents a unique therapeutic challenge displaying high population incidence with more than 60 million people worldwide. Nearly 70 % of people are provisionally responding to the treatment, but 20–60 % of patients become resistant to current antiepileptic drugs (AEDs) (WHO 2015, Epilepsy Fact Sheet No. 999). Also, there is a negative social impact of the pathology since patients and their families suffer stigma and discrimination in many parts of the world. Furthermore, patients who positively respond to the anticonvulsant treatment are subjected to high systemic concentrations of drugs to achieve therapeutically effective levels at the site of action in the central nervous system (CNS), which results in undesirable side effects that threaten their quality of life and their adherence to the treatment.

A complete assessment of the described situation is far beyond the possibilities of the present book chapter, and the sanitary problem of epilepsy (as well as other CNS diseases treated with anticonvulsant drugs) has already been described in the previous chapters. Hence, we will focus in the pharmacokinetic aspects of the problem of epilepsy treatment, including the low brain bioavailability of AEDs due to the restrictions imposed by the blood–brain barrier (BBB) and the high efflux rate of drugs from the CNS caused by the overexpression of ABC transporters at the BBB. In any case, the development of nanoformulations of AEDs seems like a promising strategy to improve their pharmacokinetic profile by increasing the fraction of drug that reaches (and stays in) the CNS, as well as by optimizing the drug’s distribution/metabolism and elimination profile.

Despite the abundance of recent works in the field of pharmaceutical nanoformulations, there is not much to be found in the particular case of epilepsy, especially if one looks for nanosystems with proven in vivo effectiveness. Therefore, this chapter begins with a short overview of the possibilities offered by the pharmaceutical nanotechnology to improve the antiepileptic therapy to continue with a detailed analysis of the methods and the results of the in vitro and in vivo evaluation of nanoformulations of AEDs reported so far.

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Acknowledgments

We thank the American Chemical Society for the permission to reproduce Fig. 1. The authors would like to thank UNLP and CONICET.

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Authors and Affiliations

  1. Quality Control of Drugs, Department of Biological Sciences, School of Sciences, Universidad Nacional de La Plata (UNLP) – Argentinean National Council for Scientific and Technical Research (CONICET) CCT La Plata, 47 & 115, La Plata, 1900, Buenos Aires, Argentina

    María E. Ruiz

  2. Nanobiomaterials Laboratory, Applied Biotechnology Institute(CINDEFI, UNLP-CONICET CCT La Plata) -School of Sciences, UniversidadNacional de La Plata, La Plata, Argentina

    Guillermo R. Castro

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  1. María E. Ruiz
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Correspondence to María E. Ruiz .

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Editors and Affiliations

  1. Laboratorio de Investigación y Desarrollo de Bioactivos (LIDeB) Faculty of Exact Sciences, National University of La Plata, La Plata, Buenos Aires, Argentina

    Alan Talevi

  2. Department of Pharmacobiology, Center for Research and Advanced Studies, Mexico City, Mexico

    Luisa Rocha

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Ruiz, M.E., Castro, G.R. (2016). Nanoformulations of Antiepileptic Drugs: In Vitro and In Vivo Studies. In: Talevi, A., Rocha, L. (eds) Antiepileptic Drug Discovery. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6355-3_16

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  • DOI: https://doi.org/10.1007/978-1-4939-6355-3_16

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