The Effect of Minor Doses of Olanzapine-Solid Lipid Nanoparticles on an Animal Model of Schizophrenia (Neurochemical and Behavioral Study) and the Side Effect

Author(s): Areeg Abd-Elrazek*, Tayseer Elnawawy

Journal Name: Drug Delivery Letters

Volume 9 , Issue 4 , 2019

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Abstract:

Background and Objective: Olanzapine (OLZ) is an atypical psychotic agent; the poor bioavailability of olanzapine is the most important issue in its treatment. The present work was carried out to evaluate the oral form of olanzapine solid lipid nanoparticles (OLZ-SLN) to overcome its poor bioavailability and compare between the effect of different doses of OLZ and OLZ-SLN on ketamineinduced schizophrenic-like symptoms. The study was extended to evaluate the adverse effects of subchronic administration of these doses of OLZ and its SLN.

Methods: OLZ-SLN was prepared by hot homogenization, particle size, zeta potential and in vitro release and entrapping efficiency studies were performed. In order to assess the effective dose in the treatment of schizophrenia, the effect of different doses of OLZ and OLZ-SLN on open field was assessed and passive avoidance tests were carried out. The test was performed to examine the effects of excitatory and inhibitory amino acids, as well as dopamine and serotonin levels in the brain regions.

Results and Conclusion: The new oral formula showed high stability and sustained release. The administration of low and high dose of OLZ-SLN equivalent to (1/10 and 1/20 from the therapeutic dose before ketamine attenuated the behavioral abnormalities by blocking the effect of ketamine-induced increase in glutamate, dopamine and serotonin levels and enhanced apoptosis were studied in the brain areas. In addition, the sub-chronic treatment with OLZ-SLN showed no adverse effect while the treatment with OLZ free form did.

Keywords: Solid lipid nanoparticles, antipsychotic drugs, hepatotoxicity, excitatory and inhibitory amino acids, monoamines, open field test, passive avoidance test.

[1]
Kharya, P.; Jain, A.; Gulbake, A. Phenylalanine-coupled solid lipid nanoparticles for brain tumor targeting, 2013.
[http://dx.doi.org/10.1007/s11051-013-2022-6]
[2]
Gastaldi, L.; Battaglia, L.; Peira, E.; Chirio, D.; Muntoni, E.; Solazzi, I.; Gallarate, M.; Dosio, F. Solid lipid nanoparticles as vehicles of drugs to the brain: current state of the art. Eur. J. Pharm. Biopharm., 2014, 87(3), 433-444.
[http://dx.doi.org/10.1016/j.ejpb.2014.05.004] [PMID: 24833004]
[3]
Blasi, P.; Giovagnoli, S.; Schoubben, A.; Ricci, M.; Rossi, C. Solid lipid nanoparticles as vehicles of drugs to the brain: Current state of the art. Eur. J. Pharm. Biopharm., 2007, 59, 454-477.
[4]
Jain, A.; Singhai, P.; Gurnany, E.; Updhayay, S.; Mody, N. Transferrin-tailored solid lipid nanoparticles as vectors for site-specific delivery of temozolomide to brain. J. Nanopart. Res., 2013, 15(3), 1518.
[http://dx.doi.org/10.1007/s11051-013-1518-4]
[5]
Sood, S.; Jawahar, N.; Jain, K.; Gowthamarajan, K.; Meyyanathan, S.N. Olanzapine Loaded Cationic Solid Lipid Nanoparticles for Improved Oral Bioavailability. Curr. Nanosci., 2013, 9(1), 26-34.
[6]
He, B.; Chen, P.; Yang, J.; Yun, Y.; Zhang, X.; Yang, R.; Shen, Z. Neuroprotective effect of 20(R)-ginsenoside Rg(3) against transient focal cerebral ischemia in rats. Neurosci. Lett., 2012, 526(2), 106-111.
[http://dx.doi.org/10.1016/j.neulet.2012.08.022] [PMID: 22925661]
[7]
Natarajan, J.; Baskaran, M.; Humtsoe, L.C.; Vadivelan, R.; Justin, A. Enhanced brain targeting efficacy of Olanzapine through solid lipid nanoparticles. Artif. Cells Nanomed. Biotechnol., 2017, 45(2), 364-371.
[http://dx.doi.org/10.3109/21691401.2016.1160402] [PMID: 27002542]
[8]
Garud, A.; Singh, D.; Garud, N. Solid Lipid Nanoparticles (SLN): Method, Characterization and Applications. Int. Curr. Pharm. J., 2012, 1(11), 384-393.
[http://dx.doi.org/10.3329/icpj.v1i11.12065]
[9]
Mukherjee, S.; Ray, S.; Thakur, R.S. Solid lipid nanoparticles: a modern formulation approach in drug delivery system. Indian J. Pharm. Sci., 2009, 71(4), 349-358.
[http://dx.doi.org/10.4103/0250-474X.57282] [PMID: 20502539]
[10]
Naseri, N.; Valizadeh, H.; Zakeri-Milani, P. Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Structure, Preparation and Application. Adv. Pharm. Bull., 2015, 5(3), 305-313.
[http://dx.doi.org/10.15171/apb.2015.043] [PMID: 26504751]
[11]
de Oliveira, L.; Fraga, D.B.; De Luca, R.D.; Canever, L.; Ghedim, F.V.; Matos, M.P.P.; Streck, E.L.; Quevedo, J.; Zugno, A.I. Behavioral changes and mitochondrial dysfunction in a rat model of schizophrenia induced by ketamine. Metab. Brain Dis., 2011, 26(1), 69-77.
[http://dx.doi.org/10.1007/s11011-011-9234-1] [PMID: 21331561]
[12]
Frohlich, J.; Van Horn, J.D. Reviewing the ketamine model for schizophrenia. J. Psychopharmacol., 2014, 28(4), 287-302.
[http://dx.doi.org/10.1177/0269881113512909] [PMID: 24257811]
[13]
Marcotte, E.R.; Pearson, D.M.; Srivastava, L.K. Animal models of schizophrenia: a critical review. J. Psychiatry Neurosci., 2001, 26(5), 395-410.
[PMID: 11762207]
[14]
Wood, S.J.; Yücel, M.; Pantelis, C.; Berk, M. Neurobiology of schizophrenia spectrum disorders: the role of oxidative stress. Ann. Acad. Med. Singapore, 2009, 38(5), 396-6.
[PMID: 19521638]
[15]
Duncan, G.E.; Miyamoto, S.; Lieberman, J.A. Chronic administration of haloperidol and olanzapine attenuates ketamine-induced brain metabolic activation. J. Pharmacol. Exp. Ther., 2003, 305(3), 999-1005.
[http://dx.doi.org/10.1124/jpet.102.048140] [PMID: 12626664]
[16]
van den Buuse, M. Modeling the positive symptoms of schizophrenia in genetically modified mice: pharmacology and methodology aspects. Schizophr. Bull., 2010, 36(2), 246-270.
[http://dx.doi.org/10.1093/schbul/sbp132] [PMID: 19900963]
[17]
Le Pen, G.; Grottick, A.J.; Higgins, G.A.; Martin, J.R.; Jenck, F.; Moreau, J.L. Spatial and associative learning deficits induced by neonatal excitotoxic hippocampal damage in rats: further evaluation of an animal model of schizophrenia. Behav. Pharmacol., 2000, 11(3-4), 257-268.
[http://dx.doi.org/10.1097/00008877-200006000-00009] [PMID: 11103880]
[18]
Asadi, A. Streptomycin-loaded PLGA-alginate nanoparticles: preparation, characterization, and assessment. Appl. Nanosci., 2014, 4(4), 455-460.
[http://dx.doi.org/10.1007/s13204-013-0219-8]
[19]
Coccurello, R.; Caprioli, A.; Ghirardi, O.; Conti, R.; Ciani, B.; Daniele, S.; Bartolomucci, A.; Moles, A. Chronic administration of olanzapine induces metabolic and food intake alterations: a mouse model of the atypical antipsychotic-associated adverse effects. Psychopharmacology (Berl.), 2006, 186(4), 561-571.
[http://dx.doi.org/10.1007/s00213-006-0368-5] [PMID: 16758241]
[20]
Uchida, S.; Kato, Y.; Hirano, K.; Kagawa, Y.; Yamada, S. Brain neurotransmitter receptor-binding characteristics in rats after oral administration of haloperidol, risperidone and olanzapine. Life Sci., 2007, 80(17), 1635-1640.
[http://dx.doi.org/10.1016/j.lfs.2007.01.038] [PMID: 17316700]
[21]
Shah, R.; Subhan, F.; Ali, G.; Ullah, I.; Ullah, S.; Shahid, M.; Ahmad, N.; Fawad, K. Olanzapine induced biochemical and histopathological changes after its chronic administration in rats. Saudi Pharm. J., 2016, 24(6), 698-704.
[http://dx.doi.org/10.1016/j.jsps.2015.06.006] [PMID: 27829813]
[22]
Gama, C.S.; Canever, L.; Panizzutti, B.; Gubert, C.; Stertz, L.; Massuda, R.; Pedrini, M.; de Lucena, D.F.; Luca, R.D.; Fraga, D.B.; Heylmann, A.S.; Deroza, P.F.; Zugno, A.I. Effects of omega-3 dietary supplement in prevention of positive, negative and cognitive symptoms: a study in adolescent rats with ketamine-induced model of schizophrenia. Schizophr. Res., 2012, 141(2-3), 162-167.
[http://dx.doi.org/10.1016/j.schres.2012.08.002] [PMID: 22954755]
[23]
El-Nabarawy, S.K.; Radwan, O.K.; El-Sisi, S.F.; Abdel-Razek, A.M. Comparative Study of Some Natural and Artificial Food Coloring Agents on Depression, Anxiety and Anti-Social Behavior in Weanling Rats. IOSR J. Pharm. Biol. Sci. Ver. III, 2015, 10(2), 2319-7676.
[24]
Ishiyama, T.; Tokuda, K.; Ishibashi, T.; Ito, A.; Toma, S.; Ohno, Y. Lurasidone (SM-13496), a novel atypical antipsychotic drug, reverses MK-801-induced impairment of learning and memory in the rat passive-avoidance test. Eur. J. Pharmacol., 2007, 572(2-3), 160-170.
[http://dx.doi.org/10.1016/j.ejphar.2007.06.058] [PMID: 17662268]
[25]
Pagel, P.; Blome, J.; Wolf, H.U. High-performance liquid chromatographic separation and measurement of various biogenic compounds possibly involved in the pathomechanism of Parkinson’s disease. J. Chromatogr. B Biomed. Sci. Appl., 2000, 746(2), 297-304.
[http://dx.doi.org/10.1016/S0378-4347(00)00348-0] [PMID: 11076082]
[26]
Heinrikson, R.L.; Meredith, S.C. Amino acid analysis by reverse-phase high-performance liquid chromatography: precolumn derivatization with phenylisothiocyanate. Anal. Biochem., 1984, 136(1), 65-74.
[http://dx.doi.org/10.1016/0003-2697(84)90307-5] [PMID: 6711815]
[27]
Nauck, M.; Warnick, G.R.; Rifai, N. Methods for measurement of LDL-cholesterol: a critical assessment of direct measurement by homogeneous assays versus calculation. Clin. Chem., 2002, 48(2), 236-254.
[PMID: 11805004]
[28]
Karatas, F.; Karatepe, M.; Baysar, A. Determination of free malondialdehyde in human serum by high-performance liquid chromatography. Anal. Biochem., 2002, 311(1), 76-79.
[http://dx.doi.org/10.1016/S0003-2697(02)00387-1] [PMID: 12441155]
[29]
Ahmad, S.T.; Arjumand, W.; Nafees, S.; Seth, A.; Ali, N.; Rashid, S.; Sultana, S. Hesperidin alleviates acetaminophen induced toxicity in Wistar rats by abrogation of oxidative stress, apoptosis and inflammation. Toxicol. Lett., 2012, 208(2), 149-161.
[http://dx.doi.org/10.1016/j.toxlet.2011.10.023] [PMID: 22093918]
[30]
Becker, A.; Grecksch, G. Ketamine-induced changes in rat behaviour: a possible animal model of schizophrenia. Test of predictive validity. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2004, 28(8), 1267-1277.
[http://dx.doi.org/10.1016/j.pnpbp.2004.06.019] [PMID: 15588753]
[31]
Tsai, G.; Coyle, J.T. Glutamatergic mechanisms in schizophrenia. Annu. Rev. Pharmacol. Toxicol., 2002, 42(1), 165-179.
[http://dx.doi.org/10.1146/annurev.pharmtox.42.082701.160735] [PMID: 11807169]
[32]
Olsen, K.A.; Rosenbaum, B. Prospective investigations of the prodromal state of schizophrenia: assessment instruments. Acta Psychiatr. Scand., 2006, 113(4), 273-282.
[http://dx.doi.org/10.1111/j.1600-0447.2005.00698.x] [PMID: 16638071]
[33]
Hamon, M.; Blier, P. Monoamine neurocircuitry in depression and strategies for new treatments. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2013, 45, 54-63.
[http://dx.doi.org/10.1016/j.pnpbp.2013.04.009] [PMID: 23602950]
[34]
Huang, L.; Liu, Y.; Jin, W.; Ji, X.; Dong, Z. Ketamine potentiates hippocampal neurodegeneration and persistent learning and memory impairment through the PKCγ-ERK signaling pathway in the developing brain. Brain Res., 2012, 1476, 164-171.
[http://dx.doi.org/10.1016/j.brainres.2012.07.059] [PMID: 22985497]
[35]
Zuo, D.; Lin, L.; Liu, Y.; Wang, C.; Xu, J.; Sun, F.; Li, L.; Li, Z.; Wu, Y. Baicalin Attenuates Ketamine-Induced Neurotoxicity in the Developing Rats: Involvement of PI3K/Akt and CREB/BDNF/Bcl-2 Pathways. Neurotox. Res., 2016, 30(2), 159-172.
[http://dx.doi.org/10.1007/s12640-016-9611-y] [PMID: 26932180]
[36]
Li, P.; Snyder, G.L.; Vanover, K.E. Dopamine Targeting Drugs for the Treatment of Schizophrenia: Past, Present and Future. Curr. Top. Med. Chem., 2016, 16(29), 3385-3403.
[http://dx.doi.org/10.2174/1568026616666160608084834] [PMID: 27291902]
[37]
Reddy, R.N.; Shariff, A. Solid Lipid Nanoparticles: an Advanced Drug Delivery System, 2013, 4(1), 161-171.


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Article Details

VOLUME: 9
ISSUE: 4
Year: 2019
Page: [308 - 320]
Pages: 13
DOI: 10.2174/2210303109666190619103230
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