Abstract
Haloperidol is a widely used antipsychotic, despite the severe motor side effects associated with its chronic use. This study was carried out to compare oral dyskinesia induced by different formulations of haloperidol-loaded nanocapsules containing caprylic/capric triglycerides, fish oil or grape seed oil (GSO) as core, as well as free haloperidol. Haloperidol-loaded lipid-core nanocapsules formulations were prepared, physicochemical characterized and administered (0.5 mg kg−1-ip) to rats for 28 days. Oral dyskinesia was evaluated acutely and subchronically and after that cell viability and free radical generation in cortex and substantia nigra. All formulations presented satisfactory physicochemical parameters. Acutely, all formulations were able to prevent oral dyskinesia development in comparison to free haloperidol, except haloperidol-loaded nanocapsules containing GSO, whose effect was only partial. After subchronic treatment, all haloperidol-loaded nanocapsules formulations prevented oral dyskinesia in relation to free drug. Also, haloperidol-loaded nanocapsules containing fish oil and GSO were more effective than caprylic/capric triglycerides nanocapsules and free haloperidol in cell viability preservation and control of free radical generation. Our findings showed that fish oil formulation may be considered as the best formulation of haloperidol-loaded lipid-core nanocapsules, being able to prevent motor side effects associated with chronic use of antipsychotic drugs, as haloperidol.
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References
Ponto T et al (2010) A prospective study on the pattern of medication use for schizophrenia in the outpatient pharmacy department, Hospital Tengku Ampuan Rahimah, Selangor, Malaysia. Methods Find Exp Clin Pharmacol 32:427–432. https://doi.org/10.1358/mf.2010.32.6.1477907
Creese I et al (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192:481–483. https://doi.org/10.1176/jnp.8.2.223
Andreassen OA, Jorgensen HA (2000). Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats—implications for tardive dyskinesia?. Prog Neurobiol 61:525–541. https://doi.org/10.1016/S0301-0082(99)00064-7
Barcelos RCS et al (2010) Effects of omega-3 essential fatty acids (omega-3 EFAs) on motor disorders and memory dysfunction typical neuroleptic-induced: behavioral and biochemical parameter. Neurotox Res 17:228–237. https://doi.org/10.1007/s12640-009-9095-0
Trevizol F et al (2011) Comparative study between two animal models of extrapyramidal movement disorders: prevention and reversion by pecan nut shell aqueous extract. Behav Brain Res 221:13–18. https://doi.org/10.1016/j.bbr.2011.02.026
Burger ME et al (2005) Acute reserpine and subchronic haloperidol treatment change synaptosomal brain glutamate uptake and elicid orofacial dyskinesia in rats. Brain Res 1031:202–210. https://doi.org/10.1016/j.brainres.2004.10.038
Zhu BT (2004) CNS dopamine oxidation and catechol-O-methyltransferase: importance in the etiology, pharmacotherapy, and dietary prevention of Parkinson’s disease. Int J Mol Med 13:343–353
Ukai W et al (2004) Neurotoxic potential of haloperidol in comparison with risperidone. Implication of Aktmediated signal changes by haloperidol. J Neural Transm 111:667–681. https://doi.org/10.1007/s00702-004-0109-z
Mitchell IJ et al (2002) Acute administration of haloperidol induces apoptosis of neurons in the striatum and substantia nigra in the rat. Neuroscience 109:89–99. https://doi.org/10.1016/S0306-4522(01)00455-9
Burger ME et al (2005) Ebselen attenuates haloperidol-induced orofacial dyskinesia and oxidative stress in rat brain. Pharmacol Biochem Behav 81:608–615. https://doi.org/10.1016/j.pbb.2005.05.002
Fachinetto R et al (2007) Valeriana officinalis does not alter the orofacial dyskinesia induced by haloperidol in rats: role of dopamine transporter. Prog Neuropsychopharmacol Biol Psychiatry 31:1478–1486. https://doi.org/10.1016/j.pnpbp.2007.06.028
Barcelos RCS et al (2011) Short term dietary fish oil supplementation improves motor deficiencies related to reserpine-induced parkinsonism in rats. Lipids 46:143–149. https://doi.org/10.1007/s11745-010-3514-0
Benvegnú DM et al (2011) Haloperidol-loaded polysorbate-coated polymeric nanocapsules increase its efficacy in the antipsychotic treatment in rats. Eur J Pharm Biopharm 77:332–336. https://doi.org/10.1016/j.ejpb.2010.12.016
Benvegnú DM et al (2012) Haloperidol-loaded polysorbate-coated polymeric nanocapsules decrease its adverse motor side effects and oxidative stress markers in rats. Neurochem Int 61:623–631. https://doi.org/10.1016/j.neuint.2012.06.015
Roversi K et al (2015) Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats. J Nanopart Res 17:199. https://doi.org/10.1007/s11051-015-2979-4
Fontana MC et al (2011) Improved efficacy in the treatment of contact dermatitis in rats by a dermatological nanomedicine containing clobetasol propionate. Eur J Pharm Biopharm 79:241–249. https://doi.org/10.1016/j.ejpb.2011.05.002
Ianiski FR et al (2012) Protective effect of meloxicam-loaded nanocapsules against amyloid-β peptide-induced damage in mice. Behav Brain Res 230:100–107. https://doi.org/10.1016/j.bbr.2012.01.055
Ourique AF et al (2011) Improved photostability and reduced skin permeation of tretinoin: Development of a semisolid nanomedicine. Eur J Pharm Biopharm 79:95–101. https://doi.org/10.1016/j.ejpb.2011.03.008
Beck RCR et al (2005) Nanostructure-coated diclofenac-loaded microparticles: preparation, morphological characterization, in vitro release and in vivo gastrointestinal tolerance. J Braz Chem Soc 16:1233–1240. https://doi.org/10.1590/S0103-50532005000700022
Gao Y et al (2010) Prostaglandin E1 encapsulated into lipid nanoparticles improves its anti-inflammatory effect with low side-effect. Int J Pharm 387:263–271. https://doi.org/10.1016/j.ijpharm.2009.12.019
Yen FL et al (2008) Nanoparticles formulation of Cuscuta chinensis prevents acetaminophen-induced hepatotoxicity in rats. Food Chem Toxicol 46:1771–1777. https://doi.org/10.1016/j.fct.2008.01.021
Nagarwal RC et al (2009) Polymeric nanoparticulate system: a potential approach for ocular drug delivery. J Control Release 136:2–13. https://doi.org/10.1016/j.jconrel.2008.12.018
Zhu L et al (2009) Chitosan-coated magnetic nanoparticles as carriers of 5-fluorouracil: preparation, characterization and cytotoxicity studies. Colloids Surf B 68:1–6. https://doi.org/10.1016/j.colsurfb.2008.07.020
Frozza RL et al (2010) Characterization of trans-resveratrol-loaded lipid-core nanocapsules and tissue distribution studies in rats. J Biomed Nanotechnol 6:694–703. https://doi.org/10.1166/jbn.2010.1161
Wohlfart S et al (2011) Kinetics of transport of doxorubicin bound to nanoparticles across the blood–brain barrier. J Control Release 154:103–107. https://doi.org/10.1016/j.jconrel.2011.05.010
Friese A et al (2000) Increase of the duration of the anticonvulsive activity of a novel NMDA receptor antagonist using poly(butylcyanoacrylate) nanoparticles as a parenteral controlled release system. Eur J Pharm Biopharm 49:103–109. https://doi.org/10.1016/S0939-6411(99)00073-9
Muthu MS et al (2009) PLGA nanoparticle formulations of risperidone: preparation and neuropharmacological evaluation. Nanomedicine 5:323–333. https://doi.org/10.1016/j.nano.2008.12.003
Parikh T et al (2010) Efficacy of surface charge in targeting pegylated nanoparticles of sulpiride to the brain. Eur J Pharm Biopharm 74:442–450. https://doi.org/10.1016/j.ejpb.2009.11.001
Dimer FA et al (2015) Nanoencapsulation improves relative bioavailability and antipsychotic effect of olanzapine in rats. J Biomed Nanotechnol 11(8):1482–1493. https://doi.org/10.1166/jbn.2015.2082
Bouchemal K et al (2004) Synthesis e characterization of polyurethane e poly (ether urethane) nanocapsules using a new technique of interfacial polycondensation combined to spontaneous emulsification. Int J Pharm 269:89–100. https://doi.org/10.1016/j.ijpharm.2003.09.025
Schaffazick SR et al. (2003) Caracterização e estabilidade físico-química de sistemas poliméricos nanoparticulados para administração de fármacos. Quím Nova 26:726–737. https://doi.org/10.1590/S0100-40422003000500017
Almeida JS et al (2009) Oil-based nanoparticles containing alternative vegetable oils (grape seed oil and almond kernel oil): preparation and characterization. Lat Am J Pharm 28:165–172. http://hdl.handle.net/10915/7742
Almeida JS et al (2010) Nanostructured systems containing rutin: in vitro antioxidant activity and photostability studies. Nanoscale Res Lett 5:1603–1610. https://doi.org/10.1007/s11671-010-9683-1
Dhanikula AB et al (2007) Long circulating lipid nanocapsules for drug detoxification. Biomaterials 26:1248–1257
Flores FC et al (2011) Nanostructured systems containing an essential oil: protection against volatilization. Quím Nova 34:968–972. https://doi.org/10.1590/S0100-40422011000600010
Baydar NG et al (2007) Characterization of grape seed and pomace oil extracts. Grasas Aceites 58:29–33
Wainwright PE (2002) Dietary essential fatty acids and brain function: a development perspective on mechanisms. Proc Nutr Soc 61:61–69. https://doi.org/10.1079/PNS2001130
Stansby ME (1969) Nutritional properties of fish oils. World Rev Nutr Diet 11:46–105. https://doi.org/10.1159/000387575
Zararsiz I et al (2006) Protective effects of omega-3 essential fatty acids against formaldehyde induced neuronal damage in prefrontal cortex of rats. Cell Biochem Funct 24:237–244. https://doi.org/10.1002/cbf.1204
Bazan NG (2006) The onset of brain injury and neurodegeneration triggers the synthesis of docosanoid neuroprotective signaling. Cell Mol Neurobiol 26:899–911. https://doi.org/10.1007/s10571-006-9064-6
Bazan NG (2007) Omega-3 fatty acids, pro-inflammatory signaling and neuroprotection. Clin Nutr Metab Care 10:136–141. https://doi.org/10.1097/MCO.0b013e32802b7030
Weiss-Angeli V et al (2008) Nanocapsules of octyl methoxycinnamate containing quercetin delayed the photodegradation of both components under ultraviolet a radiation. J Biom Nanotechnol 4:80–89. https://doi.org/10.1166/jbn.2008.004
Fessi H et al. (1989) Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm 55:r1–r4. https://doi.org/10.1016/0378-5173(89)90281-0
Hartman L, Lago BC (1973) A rapid preparation of fatty methyl esters from lipids. Lab Pract 22:475–477. https://doi.org/10.1021/ac60235a044
Reigner BG, Blesch KS (2002) Estimating the starting dose for entry into humans: principles and practice. Eur J Clin Pharmacol 12:835–845
Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Elsevier, Amsterdam
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assay. J Immunol Methods 65:55–63. https://doi.org/10.1016/0022-1759(83)90303-4
Lebel CP et al (1992) Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5:227–231
Couvreur P et al (2002) Nanocapsule technology: a review. Crit Rev Ther Drug Carrier Syst 19:99–134. https://doi.org/10.1615/CritRevTherDrugCarrierSyst.v19.i2.10
Santos-Magalhães NS et al (2000) Colloidal carriers for benzathine penicillin G: nanoemulsions and nanocapsules. Int J Pharm 208:71–80. https://doi.org/10.1016/S0378-5173(00)00546-9
Alves MP et al (2007) Human skin penetration and distribution of nimesulide from hydrophilic gels containing nanocarriers. Int J Pharm 341:215–220. https://doi.org/10.1016/j.ijpharm.2007.03.031
Milão D et al (2003) Hydrophilic gel containing nanocapsules of diclofenac: development, stability study and physico-chemical characterization. Pharmazie 58:325–329
Hunter RJ (1981) Zeta potential in colloid science: principles and applications. Academic Press, London
Tsai G et al (1998) Markers of glutamatergic neurotransmission and oxidative stress associated with tardive dyskinesia. Am J Psych 155:1207–1213. https://doi.org/10.1176/ajp.155.9.1207
Cosar M et al (2008) The neuroprotective effect of fish n-3 fatty acids in the hippocampus of diabetic rats. Nutr Neurosci 11:161–166. https://doi.org/10.1179/147683008X301531
Ozsoy O et al (2001) The influence and the mechanism of docosahexaenoic acid on a mouse model of Parkinson’s disease. Neurochem Int 49:664–670. https://doi.org/10.1016/j.neuint.2011.06.012
Acknowledgements
Authors are grateful to Ministério da Ciência e Tecnologia/Conselho Nacional de Desenvolvimento Científico e Tecnológico (MCT/CNPq-nº62/2008), Coordenação de Aperfeiçoamento Pessoal de Nível Superior (CAPES) and Programa de Apoio a Pós-Graduação/ Pró Reitoria de Pós-Graduação e Pesquisa da Universidade Federal de Santa Maria (PROAP/PRPGP-UFSM) by financial support.
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Benvegnú, D.M., Roversi, K., Barcelos, R.C.S. et al. Effects of Fish and Grape Seed Oils as Core of Haloperidol-Loaded Nanocapsules on Oral Dyskinesia in Rats. Neurochem Res 43, 477–487 (2018). https://doi.org/10.1007/s11064-017-2444-0
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DOI: https://doi.org/10.1007/s11064-017-2444-0