Evaluation of Quetiapine Fumarate and its Solid Lipid Nanoparticles as antipsychotic drug in rat model of schizophrenia
DOI:
https://doi.org/10.15419/bmrat.v4i08.203Keywords:
Biology, Antipsychotic drugs, Catecholamines, Excitatory and inhibitory amino acids, Nanoparticles, Schizophrenia, MedicineAbstract
Background: The present study compares the efficacy of quetiapine fumarate (QF) and QF-loaded solid lipid nanoparticles (QFSLN) as antipsychotic drugs for schizophrenia.
Methods: To induce schizophrenia-like symptoms, a group of rats was injected intraperitoneally (i.p.) with ketamine (25mg/kg b.w.) for 1 week to establish a rat model of schizophrenia. The incidence of schizophrenic symptoms was estimated to be equivalent to the control group. To estimate the pronounced antipsychotic effect of QF, a low dose (LD) of 10 mg/kg b.w. and a high dose (HD) of 30 mg /kg b.w. were orally administrated to two groups of rats (designated L.QF and H.QF) for 3 weeks (2 weeks without ketamine injection; the last week with ketamine). To achieve the optimal therapeutic response of QF drug, 2 other groups of rats were administered orally the equivalent low and high doses of QF in its solid lipid nanoparticle form (L.QFSLN) and (H.QFSLN) for 3 weeks in the same manner. The treatments were given after 1 h of ketamine injection. To assess the effect of different doses of treatment on hyperlocomotion and cognitive impairment induced by ketamine, an open field test and passive avoidance test were conducted. In addition, excitatory and inhibitory amino acids, as well as catecholamines, were estimated in brain regions (cortex and hippocampus). The study was extended to estimate the side effects of different treatments on hepatorenal functions and lipid profile. Additionally, samples were subjected to immunohistochemical analysis.
Results: QFSLN treatment showed enhanced effect over QF in a dose-dependent manner with minimal side effects in schizophrenic rats. In addition, immunohistochemical examinations of brain tissues confirmed the biochemical data.
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<li class="show">Lodge, D.J., and Grace, A.A. (2011). Developmental pathology, dopamine, stress and schizophrenia. International Journal of Developmental Neuroscience 29, 207-213. <a href="https://doi.org/10.1016/j.ijdevneu.2010.08.002">https://doi.org/10.1016/j.ijdevneu.2010.08.002</a></li>
<li class="show">Maeshima, H., Ohnuma, T., Sakai, Y., Shibata, N., Baba, H., Ihara, H., Higashi, M., Ohkubo, T., Nozawa, E., and Abe, S. (2007). Increased plasma glutamate by antipsychotic medication and its relationship to glutaminase 1 and 2 genotypes in schizophrenia—Juntendo University Schizophrenia Projects (JUSP). Progress in Neuro-Psychopharmacology and Biological Psychiatry 31, 1410-1418. <a href="https://doi.org/10.1016/j.pnpbp.2007.06.009">https://doi.org/10.1016/j.pnpbp.2007.06.009</a></li>
<li class="show">Malhotra, A.K., Pinals, D.A., Adler, C.M., Elman, I., Clifton, A., Pickar, D., and Breier, A. (1997). Ketamine-induced exacerbation of psychotic symptoms and cognitive impairment in neuroleptic-free schizophrenics. Neuropsychopharmacology 17, 141-150. <a href="https://doi.org/10.1016/S0893-133X(97)00036-5">https://doi.org/10.1016/S0893-133X(97)00036-5</a></li>
<li class="show">Malhotra, A.K., Pinals, D.A., Weingartner, H., Sirocco, K., Missar, C.D., Pickar, D., and Breier, A. (1996). NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers. Neuropsychopharmacology 14, 301-307. <a href="https://doi.org/10.1016/0893-133X(95)00137-3">https://doi.org/10.1016/0893-133X(95)00137-3</a></li>
<li class="show">McLamb, R.L., Williams, L.R., Nanry, K.P., Wilson, W.A., and Tilson, H.A. (1990). MK-801 impedes the acquisition of a spatial memory task in rats. Pharmacology Biochemistry and Behavior 37, 41-45. <a href="https://doi.org/10.1016/0091-3057(90)90038-J">https://doi.org/10.1016/0091-3057(90)90038-J</a></li>
<li class="show">Mehnert, W., and Mäder, K. (2001). Solid lipid nanoparticles: production, characterization and applications. Advanced drug delivery reviews 47, 165-196. <a href="https://doi.org/10.1016/S0169-409X(01)00105-3">https://doi.org/10.1016/S0169-409X(01)00105-3</a></li>
<li class="show">Meyer, J.M., and Koro, C.E. (2004). The effects of antipsychotic therapy on serum lipids: a comprehensive review. Schizophrenia research 70, 1-17. <a href="https://doi.org/10.1016/j.schres.2004.01.014">https://doi.org/10.1016/j.schres.2004.01.014</a></li>
<li class="show">MuÈller, R.H., MaÈder, K., and Gohla, S. (2000). Solid lipid nanoparticles (SLN) for controlled drug delivery–a review of the state of the art. European journal of pharmaceutics and biopharmaceutics 50, 161-177. <a href="https://doi.org/10.1016/S0939-6411(00)00087-4">https://doi.org/10.1016/S0939-6411(00)00087-4</a></li>
<li class="show">Narala, A., and Veerabrahma, K. (2013). Preparation, characterization and evaluation of quetiapine fumarate solid lipid nanoparticles to improve the oral bioavailability. Journal of pharmaceutics 2013. <a href="https://doi.org/10.1155/2013/265741">https://doi.org/10.1155/2013/265741</a></li>
<li class="show">Olesen, J., Gustavsson, A., Svensson, M., Wittchen, H.U., and Jönsson, B. (2012). The economic cost of brain disorders in Europe. European journal of neurology 19, 155-162. <a href="https://doi.org/10.1111/j.1468-1331.2011.03590.x">https://doi.org/10.1111/j.1468-1331.2011.03590.x</a></li>
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2017-08-07
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Copyright The Author(s) 2017. This article is published with open access by BioMedPress. This article is distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0) which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
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Evaluation of Quetiapine Fumarate and its Solid Lipid Nanoparticles as antipsychotic drug in rat model of schizophrenia. (2017). Biomedical Research and Therapy, 4(08), 1480-1497. https://doi.org/10.15419/bmrat.v4i08.203
