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New perspectives of nanoneuroprotection, nanoneuropharmacology and nanoneurotoxicity: modulatory role of amino acid neurotransmitters, stress, trauma, and co-morbidity factors in nanomedicine

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Abstract

Recent advancement in nanomedicine suggests that nanodrug delivery using nanoformulation of drugs or use of nanoparticles for neurodiagnostic and/or neurotherapeutic purposes results in superior effects than the conventional drugs or parent compounds. This indicates a bright future for nanomedicine in treating neurological diseases in clinics. However, the effects of nanoparticles per se in inducing neurotoxicology by altering amino acid neurotransmitters, if any, are still being largely ignored. The main aim of nanomedicine is to enhance the drug availability within the central nervous system (CNS) for greater therapeutic successes. However, once the drug together with nanoparticles enters into the CNS compartments, the fate of nanomaterial within the brain microenvironment is largely remained unknown. Thus, to achieve greater success in nanomedicine, our knowledge in understanding nanoneurotoxicology in detail is utmost important. In addition, how co-morbidity factors associated with neurological disease, e.g., stress, trauma, hypertension or diabetes, may influence the neurotherapeutic potentials of nanomedicine are also necessary to explore the details. Recent research in our laboratory demonstrated that engineered nanoparticles from metals or titanium nanowires used for nanodrug delivery in laboratory animals markedly influenced the CNS functions and alter amino acid neurotransmitters in healthy animals. These adverse reactions of nanoparticles within the CNS are further aggravated in animals with different co-morbidity factors viz., stress, diabetes, trauma or hypertension. This effect, however, depends on the composition and dose of the nanomaterials used. On the other hand, nanodrug delivery by TiO2 nanowires enhanced the neurotherapeutic potential of the parent compounds in CNS injuries in healthy animals and do not alter amino acids balance. However, in animals with any of the above co-morbidity factors, high dose of nanodrug delivery is needed to achieve some neuroprotection. Taken together, it appears that while exploring new nanodrug formulations for neurotherapeutic purposes, co-morbidly factors and composition of nanoparticles require more attention. Furthermore, neurotoxicity caused by nanoparticles per se following nanodrug delivery may be examined in greater detail with special regards to changes in amino acid balance in the CNS.

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Acknowledgments

The views expressed in this report are solely of the authors and in no way represent official positions of any granting authority or government organizations listed in the financial and competing interests disclosure.

Conflict of interest

The authors’ research was supported by grants from the European Office of Aerospace Research & Development (EOARD), London, UK; Wright Patterson Air Force Base (WPAFB), Dayton, OH, USA; Laboratory support from US Food & Drug Administration (FDA), National Center for Toxicological Research (NCTR), Jefferson, AR, USA; Research support from Uppsala University (UU), Sweden; Department of Biotechnology, Ministry of Science & Technology, Govt. of India, New Delhi, India; Medical Research Council, New Delhi, India; Swedish Medical Research Council, Stockholm, Sweden; Alexander von Humboldt Foundation, Bonn, Germany; Göran Gustafsson Foundation, Stockholm, Sweden; and Astra-Zeneca, Mölndal, Sweden. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

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Authors and Affiliations

  1. Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, University Hospital, Uppsala University, 75185, Uppsala, Sweden

    Hari S. Sharma & Aruna Sharma

  2. Uppsala University, Frödingsgatan 12:28, 75421, Uppsala, Sweden

    Hari S. Sharma

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  1. Hari S. Sharma
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  2. Aruna Sharma
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Correspondence to Hari S. Sharma.

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A part of this concept paper was presented as policy issues in Society for Neuroscience 41st Meeting, San Diego, CA, October 13th, 2010; 42nd Society for Neuroscience Meeting, Washington DC, November 13, 2011; and 43rd Society for Neuroscience Meeting, New Orleans, LA, 12th October, 2012 on Nanomedicine and its Future.

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Sharma, H.S., Sharma, A. New perspectives of nanoneuroprotection, nanoneuropharmacology and nanoneurotoxicity: modulatory role of amino acid neurotransmitters, stress, trauma, and co-morbidity factors in nanomedicine. Amino Acids 45, 1055–1071 (2013). https://doi.org/10.1007/s00726-013-1584-z

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