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14-02-2024 | Amnesia | Original Article

New curcumin-loaded nanocapsules as a therapeutic alternative in an amnesia model

Authors: Karline da Costa Rodrigues, Manoel Rodrigues da Silva Neto, Victor dos Santos Barboza, Sandra Elisa Hass, Rodrigo de Almeida Vaucher, Janice Luehring Giongo, Ricardo Frederico Schumacher, Ethel Antunes Wilhelm, Cristiane Luchese

Published in: Metabolic Brain Disease | Issue 4/2024

Abstract

This study aimed to investigate the action of two different formulations of curcumin (Cur)-loaded nanocapsules (Nc) (Eudragit [EUD] and poly (ɛ-caprolactone) [PCL]) in an amnesia mice model. We also investigated the formulations’ effects on scopolamine-induced (SCO) depressive- and anxiety-like comorbidities, the cholinergic system, oxidative parameters, and inflammatory markers. Male Swiss mice were randomly divided into five groups (n = 8): group I (control), group II (Cur PCL Nc 10 mg/kg), group III (Cur EUD Nc 10 mg/kg), group IV (free Cur 10 mg/kg), and group V (SCO). Treatments with Nc or Cur (free) were performed daily or on alternate days. After 30 min of treatment, the animals received the SCO and were subjected to behavioral tests 30 min later (Barnes maze, open-field, object recognition, elevated plus maze, tail suspension tests, and step-down inhibitory avoidance tasks). The animals were then euthanized and tissue was removed for biochemical assays. Our results demonstrated that Cur treatment (Nc or free) protected against SCO-induced amnesia and depressive-like behavior. The ex vivo assays revealed lower acetylcholinesterase (AChE) and catalase (CAT) activity, reduced thiobarbituric species (TBARS), reactive species (RS), and non-protein thiols (NSPH) levels, and reduced interleukin-6 (IL-6) and tumor necrosis factor (TNF) expression. The treatments did not change hepatic markers in the plasma of mice. After treatments on alternate days, Cur Nc had a more significant effect than the free Cur protocol, implying that Cur may have prolonged action in Nc. This finding supports the concept that it is possible to achieve beneficial effects in nanoformulations, and treatment on alternate days differs from the free Cur protocol regarding anti-amnesic effects in mice.

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Aebi H (1984) [13] Catalase in vitro. pp 121–126

Akhtar A, Andleeb A, Waris TS et al (2021) Neurodegenerative diseases and effective drug delivery: a review of challenges and novel therapeutics. J Control Release 330:1152–1167. https://doi.org/10.1016/j.jconrel.2020.11.021CrossRefPubMed

Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB (2007) Bioavailability of curcumin: problems and promises. Mol Pharm 4:807–818. https://doi.org/10.1021/mp700113rCrossRefPubMed

Bagheri H, Ghasemi F, Barreto GE et al (2020) Effects of curcumin on mitochondria in neurodegenerative diseases. BioFactors 46:5–20. https://doi.org/10.1002/biof.1566CrossRefPubMed

Balez R, Ooi L (2016) Getting to NO Alzheimer’s disease: neuroprotection versus neurotoxicity mediated by nitric oxide. Oxidative Med Cell Longev 2016:1–8. https://doi.org/10.1155/2016/3806157CrossRef

Barbara R, Belletti D, Pederzoli F et al (2017) Novel curcumin loaded nanoparticles engineered for blood-brain barrier crossing and able to disrupt Abeta aggregates. Int J Pharm 526:413–424. https://doi.org/10.1016/j.ijpharm.2017.05.015CrossRefPubMed

Battaglia S, Fabius JH, Moravkova K et al (2022) The neurobiological correlates of gaze perception in healthy individuals and neurologic patients. Biomedicines 10:627. https://doi.org/10.3390/biomedicines10030627CrossRefPubMedPubMedCentral

Boiangiu RS, Brinza I, Hancianu M et al (2020) Cognitive facilitation and antioxidant effects of an essential oil mix on scopolamine-induced amnesia in rats: molecular modeling of in vitro and in vivo approaches. Molecules 25:1519. https://doi.org/10.3390/molecules25071519CrossRefPubMedPubMedCentral

Borghans B (2015) Animal models for posttraumatic stress disorder: an overview of what is used in research. World J Psychiatry 5:387. https://doi.org/10.5498/wjp.v5.i4.387CrossRefPubMedPubMedCentral

Bostancıklıoğlu M (2019) An update on the interactions between Alzheimer’s disease, autophagy and inflammation. Gene 705:157–166. https://doi.org/10.1016/j.gene.2019.04.040CrossRefPubMed

Bradford M (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254. https://doi.org/10.1006/abio.1976.9999CrossRefPubMed

Cheon SY, Koo B-N, Kim SY et al (2021) Scopolamine promotes neuroinflammation and delirium-like neuropsychiatric disorder in mice. Sci Rep 11:8376. https://doi.org/10.1038/s41598-021-87790-yCrossRefPubMedPubMedCentral

Chopra H, Dey PS, Das D et al (2021) Curcumin nanoparticles as promising therapeutic agents for drug targets. Molecules 26:4998. https://doi.org/10.3390/molecules26164998CrossRefPubMedPubMedCentral

Coradini K, Friedrich RB, Fonseca FN et al (2015) A novel approach to arthritis treatment based on resveratrol and curcumin co-encapsulated in lipid-core nanocapsules: in vivo studies. Eur J Pharm Sci 78:163–170. https://doi.org/10.1016/j.ejps.2015.07.012CrossRefPubMed

da Costa Rodrigues K, Leivas de Oliveira R, da Silva CJ et al (2022) A new arylsulfanyl-benzo-2,1,3-thiadiazoles derivative produces an anti-amnesic effect in mice by modulating acetylcholinesterase activity. Chem Biol Interact 351:109736. https://doi.org/10.1016/j.cbi.2021.109736CrossRefPubMed

Das S, Suresh PK, Desmukh R (2010) Design of Eudragit RL 100 nanoparticles by nanoprecipitation method for ocular drug delivery. Nanomedicine 6:318–323. https://doi.org/10.1016/j.nano.2009.09.002CrossRefPubMed

dos Santos RB, Nakama KA, Pacheco CO et al (2021) Curcumin-loaded nanocapsules: influence of surface characteristics on technological parameters and potential antimalarial activity. Mater Sci Eng C 118:111356. https://doi.org/10.1016/j.msec.2020.111356CrossRef

Dos Santos RB, Funguetto-Ribeiro AC, Maciel TR et al (2022) In vivo and in vitro per se effect evaluation of Polycaprolactone and Eudragit® RS100-based nanoparticles. Biomed Pharmacother 153:113410. https://doi.org/10.1016/j.biopha.2022.113410CrossRefPubMed

Ege D (2021) Action mechanisms of curcumin in Alzheimer’s disease and its brain targeted delivery. Materials 14:3332. https://doi.org/10.3390/ma14123332CrossRefPubMedPubMedCentral

Eghbaliferiz S, Farhadi F, Barreto GE et al (2020) Effects of curcumin on neurological diseases: focus on astrocytes. Pharmacol Rep 72:769–782. https://doi.org/10.1007/s43440-020-00112-3CrossRefPubMed

Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77. https://doi.org/10.1016/0003-9861(59)90090-6CrossRefPubMed

Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95. https://doi.org/10.1016/0006-2952(61)90145-9CrossRefPubMed

Faul F, Erdfelder E, Lang A-G, Buchner A (2007) G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39:175–191. https://doi.org/10.3758/BF03193146CrossRefPubMed

Francis PT, Palmer AM, Snape M, Wilcock GK (1999) The cholinergic hypothesis of Alzheimer’s disease: a review of progress. J Neurol Neurosurg Psychiatry 66:137–147. https://doi.org/10.1136/jnnp.66.2.137CrossRefPubMedPubMedCentral

Garthwaite J (1991) Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci 14:60–67. https://doi.org/10.1016/0166-2236(91)90022-MCrossRefPubMed

Giacomeli R, Izoton JC, dos Santos RB et al (2019) Neuroprotective effects of curcumin lipid-core nanocapsules in a model Alzheimer’s disease induced by β-amyloid 1-42 peptide in aged female mice. Brain Res 1721:146325. https://doi.org/10.1016/j.brainres.2019.146325CrossRefPubMed

Giacomeli R, de Gomes MG, Reolon JB et al (2020) Chrysin loaded lipid-core nanocapsules ameliorates neurobehavioral alterations induced by β-amyloid1-42 in aged female mice. Behav Brain Res 390:112696. https://doi.org/10.1016/j.bbr.2020.112696CrossRefPubMed

Giongo JL, de Almeida VR, Sagrillo MR et al (2017) Anti-inflammatory effect of geranium nanoemulsion macrophages induced with soluble protein of Candida albicans. Microb Pathog 110:694–702. https://doi.org/10.1016/j.micpath.2017.01.056CrossRefPubMed

Gomes GS, Maciel TR, Piegas EM et al (2018) Optimization of Curcuma oil/quinine-loaded Nanocapsules for malaria treatment. AAPS PharmSciTech 19:551–564. https://doi.org/10.1208/s12249-017-0854-6CrossRefPubMed

Helli B, Gerami H, Kavianpour M et al (2021) Curcumin Nanomicelle improves lipid profile, stress oxidative factors and inflammatory markers in patients undergoing coronary elective angioplasty; a randomized clinical trial. Endocr Metab Immune Disord Drug Targets 21:2090–2098. https://doi.org/10.2174/1871530321666210104145231CrossRefPubMed

Hoover DB (2017) Cholinergic modulation of the immune system presents new approaches for treating inflammation. Pharmacol Ther 179:1–16. https://doi.org/10.1016/j.pharmthera.2017.05.002CrossRefPubMedPubMedCentral

Hurley LL, Akinfiresoye L, Nwulia E et al (2013) Antidepressant-like effects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF. Behav Brain Res 239:27–30. https://doi.org/10.1016/j.bbr.2012.10.049CrossRefPubMed

Hussain H, Ahmad S, Shah SWA et al (2021) Neuroprotective potential of synthetic mono-carbonyl curcumin analogs assessed by molecular docking studies. Molecules 26:7168. https://doi.org/10.3390/molecules26237168CrossRefPubMedPubMedCentral

Hussain H, Ahmad S, Shah SWA et al (2022) Attenuation of scopolamine-induced amnesia via cholinergic modulation in mice by synthetic curcumin analogs. Molecules 27:2468. https://doi.org/10.3390/molecules27082468CrossRefPubMedPubMedCentral

Ighodaro OM, Akinloye OA (2018) First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): their fundamental role in the entire antioxidant defence grid. Alexandria Journal of Medicine 54:287–293. https://doi.org/10.1016/j.ajme.2017.09.001CrossRef

Ismail Z, Elbayoumi H, Fischer CE et al (2017) Prevalence of depression in patients with mild cognitive impairment. JAMA Psychiatry 74:58. https://doi.org/10.1001/jamapsychiatry.2016.3162CrossRefPubMed

Jäger E, Venturini CG, Poletto FS et al (2009) Sustained release from lipid-core Nanocapsules by varying the core viscosity and the particle surface area. J Biomed Nanotechnol 5:130–140. https://doi.org/10.1166/jbn.2009.1004CrossRefPubMed

Jaguezeski AM, Gündel SS, Favarin FR et al (2019) Low-dose curcumin-loaded Eudragit L-100-nanocapsules in the diet of dairy sheep increases antioxidant levels and reduces lipid peroxidation in milk. J Food Biochem 43. https://doi.org/10.1111/jfbc.12942

Juszczyk G, Mikulska J, Kasperek K et al (2021) Chronic stress and oxidative stress as common factors of the pathogenesis of depression and Alzheimer’s disease: the role of antioxidants in prevention and treatment. Antioxidants 10:1439. https://doi.org/10.3390/antiox10091439CrossRefPubMedPubMedCentral

Kilimann I, Hausner L, Fellgiebel A et al (2016) Parallel atrophy of cortex and basal forebrain cholinergic system in mild cognitive impairment. Cerebral Cortex bhw019. https://doi.org/10.1093/cercor/bhw019

Loetchutinat C, Kothan S, Dechsupa S et al (2005) Spectrofluorometric determination of intracellular levels of reactive oxygen species in drug-sensitive and drug-resistant cancer cells using the 2′,7′-dichlorofluorescein diacetate assay. Radiat Phys Chem 72:323–331. https://doi.org/10.1016/j.radphyschem.2004.06.011CrossRef

Manconi M, Manca ML, Escribano-Ferrer E et al (2019) Nanoformulation of curcumin-loaded eudragit-nutriosomes to counteract malaria infection by a dual strategy: improving antioxidant intestinal activity and systemic efficacy. Int J Pharm 556:82–88. https://doi.org/10.1016/j.ijpharm.2018.11.073CrossRefPubMed

Mandal M, Jaiswal P, Mishra A (2020) Role of curcumin and its nanoformulations in neurotherapeutics: a comprehensive review. J Biochem Mol Toxicol 34. https://doi.org/10.1002/jbt.22478

Matias JN, Achete G, dos Santos Campanari GS et al (2021) A systematic review of the antidepressant effects of curcumin: beyond monoamines theory. Aust N Z J Psychiatr 55:451–462. https://doi.org/10.1177/0004867421998795CrossRef

Naqvi F, Haider S, Naqvi F et al (2019) A comparative study showing greater effects of curcumin compared to donepezil on memory function in rats. Pak J Pharm Sci 32:53–60PubMed

Nuzzo D (2021) Role of natural antioxidants on neuroprotection and Neuroinflammation. Antioxidants 10:608. https://doi.org/10.3390/antiox10040608CrossRefPubMedPubMedCentral

Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358. https://doi.org/10.1016/0003-2697(79)90738-3CrossRefPubMed

Panzarini E, Mariano S, Tacconi S et al (2020) Novel therapeutic delivery of Nanocurcumin in central nervous system related disorders. Nanomaterials 11:2. https://doi.org/10.3390/nano11010002CrossRefPubMedPubMedCentral

Pignatello R, Ricupero N, Bucolo C et al (2006) Preparation and characterization of Eudragit retard nanosuspensions for the ocular delivery of cloricromene. AAPS PharmSciTech 7:E192–E198. https://doi.org/10.1208/pt070127CrossRefPubMedPubMedCentral

Pompl PN, Mullan MJ, Bjugstad K, Arendash GW (1999) Adaptation of the circular platform spatial memory task for mice: use in detecting cognitive impairment in the APPSW transgenic mouse model for Alzheimer’s disease. J Neurosci Methods 87:87–95. https://doi.org/10.1016/S0165-0270(98)00169-1CrossRefPubMed

Ponchel G (1998) Specific and non-specific bioadhesive particulate systems for oral delivery to the gastrointestinal tract. Adv Drug Deliv Rev 34:191–219. https://doi.org/10.1016/S0169-409X(98)00040-4CrossRefPubMed

Rahimzadegan M, Soodi M (2018) Comparison of memory impairment and oxidative stress following single or repeated doses Administration of Scopolamine in rat Hippocampus. Basic Clin Neurosci J 9:5–14. https://doi.org/10.29252/nirp.bcn.9.1.5CrossRef

Razavi BM, Hosseinzadeh H (2020) Antioxidant effects of Curcuma longa and its active constituent, curcumin, for the therapy of neurological disorders. In: Oxidative Stress and Dietary Antioxidants in Neurological Diseases. Elsevier, pp 249–269

Reddy PH, Manczak M, Yin X et al (2018) Protective effects of Indian spice curcumin against amyloid-β in Alzheimer’s disease. J Alzheimers Dis 61:843–866. https://doi.org/10.3233/JAD-170512CrossRefPubMedPubMedCentral

Sakaguchi M, Koseki M, Wakamatsu M, Matsumura E (2006) Effects of systemic administration of β-casomorphin-5 on learning and memory in mice. Eur J Pharmacol 530:81–87. https://doi.org/10.1016/j.ejphar.2005.11.014CrossRefPubMed

Sarandol A, Sarandol E, Eker SS, Erdinc S, Vatansever E, Kirli S (2007) Major depressive disorder isaccompanied with oxidative stress: short-term antidepressant treatment does not alter oxidative-antioxidative systems. Hum Psychopharmacol 22(2):67–73. https://doi.org/10.1002/hup.829CrossRefPubMed

Sarter M, Bodewitz G, Stephens DN (1988) Attenuation of scopolamine-induced impairment of spontaneous alternation behaviour by antagonist but not inverse agonist and agonist ?-carbolines. Psychopharmacology 94:491–495. https://doi.org/10.1007/BF00212843CrossRefPubMed

Seo H-J, Wang S-M, Han C et al (2015) Curcumin as a putative antidepressant. Expert Rev Neurother 15:269–280. https://doi.org/10.1586/14737175.2015.1008457CrossRefPubMed

Soliman GM, Redon R, Sharma A et al (2014) Miktoarm star polymer based multifunctional traceable Nanocarriers for efficient delivery of poorly water soluble pharmacological agents. Macromol Biosci 14:1312–1324. https://doi.org/10.1002/mabi.201400123CrossRefPubMed

Soltani S, Zakeri-Milani P, Barzegar-Jalali M, Jelvehgari M (2016) Design of eudragit RL nanoparticles by nanoemulsion method as carriers for ophthalmic drug delivery of ketotifen fumarate. Iran J Basic Med Sci 19:550–560PubMedPubMedCentral

SoukhakLari R, Moezi L, Pirsalami F et al (2018) Curcumin ameliorates scopolamine-induced mice memory retrieval deficit and restores hippocampal p-Akt and p-GSK-3β. Eur J Pharmacol 841:28–32. https://doi.org/10.1016/j.ejphar.2018.10.012CrossRefPubMed

Souza MA, Magni DV, Guerra GP et al (2012) Involvement of hippocampal CAMKII/CREB signaling in the spatial memory retention induced by creatine. Amino Acids 43:2491–2503. https://doi.org/10.1007/s00726-012-1329-4CrossRefPubMed

Stanciu GD, Luca A, Rusu RN et al (2019) Alzheimer’s disease pharmacotherapy in relation to cholinergic system involvement. Biomolecules 10:40. https://doi.org/10.3390/biom10010040CrossRefPubMedPubMedCentral

Stangherlin EC, Rocha JBT, Nogueira CW (2009) Diphenyl ditelluride impairs short-term memory and alters neurochemical parameters in young rats. Pharmacol Biochem Behav 91:430–435. https://doi.org/10.1016/j.pbb.2008.08.020CrossRefPubMed

Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85:367–370. https://doi.org/10.1007/BF00428203CrossRefPubMed

Tang M, Taghibiglou C (2017) The mechanisms of action of curcumin in Alzheimer’s disease. J Alzheimers Dis 58:1003–1016. https://doi.org/10.3233/JAD-170188CrossRefPubMed

Teixeira MI, Lopes CM, Amaral MH, Costa PC (2020) Current insights on lipid nanocarrier-assisted drug delivery in the treatment of neurodegenerative diseases. Eur J Pharm Biopharm 149:192–217. https://doi.org/10.1016/j.ejpb.2020.01.005CrossRefPubMed

Umerska A, Gaucher C, Oyarzun-Ampuero F et al (2018) Polymeric nanoparticles for increasing oral bioavailability of curcumin. Antioxidants 7:46. https://doi.org/10.3390/antiox7040046CrossRefPubMedPubMedCentral

Vieira SM, Michels LR, Roversi K et al (2016) A surface modification of clozapine-loaded nanocapsules improves their efficacy: a study of formulation development and biological assessment. Colloids Surf B Biointerfaces 145:748–756. https://doi.org/10.1016/j.colsurfb.2016.05.065CrossRefPubMed

Villemagne VL, Burnham S, Bourgeat P et al (2013) Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol 12:357–367. https://doi.org/10.1016/S1474-4422(13)70044-9CrossRefPubMed

Walsh RN, Cummins RA (1976) The open-field test: a critical review. Psychol Bull 83:482–504. https://doi.org/10.1037/0033-2909.83.3.482CrossRefPubMed

Wang M, Jiang S, Zhou L et al (2019) Potential mechanisms of action of curcumin for Cancer prevention: focus on cellular signaling pathways and miRNAs. Int J Biol Sci 15:1200–1214. https://doi.org/10.7150/ijbs.33710CrossRefPubMedPubMedCentral

Weiss C, Carriere M, Fusco L et al (2020) Toward nanotechnology-enabled approaches against the COVID-19 pandemic. ACS Nano 14:6383–6406. https://doi.org/10.1021/acsnano.0c03697CrossRefPubMed

Wu D, Xu X, Sun N et al (2020) AGLPM and QMDDQ peptides exert a synergistic action on memory improvement against scopolamine-induced amnesiac mice. Food Funct 11:10925–10935. https://doi.org/10.1039/D0FO02570DCrossRefPubMed

Yanagisawa D, Amatsubo T, Morikawa S et al (2011) In vivo detection of amyloid β deposition using 19F magnetic resonance imaging with a 19F-containing curcumin derivative in a mouse model of Alzheimer’s disease. Neuroscience 184:120–127. https://doi.org/10.1016/j.neuroscience.2011.03.071CrossRefPubMed

Yavarpour-Bali H, Ghasemi-Kasman M, Pirzadeh M (2019) Curcumin-loaded nanoparticles: a novel therapeutic strategy in treatment of central nervous system disorders. Int J Nanomedicine 14:4449–4460. https://doi.org/10.2147/IJN.S208332CrossRefPubMedPubMedCentral

Zeng M, Xu J, Luo Q et al (2020) Constructing antibacterial polymer nanocapsules based on pyridine quaternary ammonium salt. Mater Sci Eng C 108:110383. https://doi.org/10.1016/j.msec.2019.110383CrossRef

Title: New curcumin-loaded nanocapsules as a therapeutic alternative in an amnesia model
Authors: Karline da Costa Rodrigues
Manoel Rodrigues da Silva Neto
Victor dos Santos Barboza
Sandra Elisa Hass
Rodrigo de Almeida Vaucher
Janice Luehring Giongo
Ricardo Frederico Schumacher
Ethel Antunes Wilhelm
Cristiane Luchese
Publication date: 14-02-2024
Publisher: Springer US
Keywords: Amnesia
Cytokines
Published in: Metabolic Brain Disease / Issue 4/2024
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-023-01329-w

Keynote webinar | Spotlight on medication adherence

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New curcumin-loaded nanocapsules as a therapeutic alternative in an amnesia model

Abstract

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Keynote webinar | Spotlight on medication adherence

Springer Medicine

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