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

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 nanoparticlesrequire 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.