Use of liposome-encapsulated estetrol for treatment of neonatal hypoxic-ischemic encephalopathy.

Brain; Drug-in cyclodextrin in liposome (DCL) system with E4; Estetrol; Liposome-encapsulated E4; Neonatal HIE; Liposomes; Estrogens; Rats; Animals; Liposomes/metabolism; Liposomes/pharmacology; Estrogens/metabolism; Neurons/metabolism; Estetrol/metabolism; Estetrol/pharmacology; Estetrol/therapeutic use; Hypoxia-Ischemia, Brain/drug therapy; Hypoxia-Ischemia, Brain/metabolism; Hypoxia-Ischemia, Brain; Neurons; Neuroscience (all); Molecular Biology; Neurology (clinical); Developmental Biology; General Neuroscience

Abstract :

[en] Estetrol (E4) is a natural estrogen synthesized only during pregnancy. It has strong neuroprotective and antioxidative activities. The aim of the present study was to define the neuroprotective potency of E4 encapsulated either in liposome (Lipo-E4) or in drug-in cyclodextrin (HP-β-CD) in liposome (DCL) system, and compare them with a single use of E4. In vitro studies were performed in an oxidative stress model of primary hippocampal neuronal cell cultures, followed by the lactate dehydrogenase activity and cell proliferation assays. In vivo studies were conducted by using a model of neonatal hypoxic-ischemic encephalopathy in immature rat pups. Brain samples were studied by (immuno)histochemistry for the detection of survived cells, expression of microtubule-associated protein-2, myelin basic protein, doublecortin and vascular-endothelial growth factor. Concentrations of glial fibrillary acidic protein in blood serum were studied by ELISA. In vitro, cell proliferation was significantly up-regulated in cultures treated either by DCL-E4 or E4 compared to the control cells, whereas DCL-E4 treated cells had significantly higher survival rate than the cells treated by E4 alone. Evaluation of brain samples showed that DCL-E4 and a high dose of E4 alone significantly preserve the grey and the white matter loses, and diminish GFAP expression in blood. Although DCL-E4 and E4 have similar effect on neurogenesis in the hippocampus and the cortex, DCL-E4 treatment significantly up-regulates angiogenesis in the hippocampus compared to a single use of E4. Present work reveals for the first time that liposome-encapsulated E4 might be a better alternative to a single use of E4.

Disciplines :

Pediatrics
Neurology
Pharmacy, pharmacology & toxicology

Author, co-author :

Tskitishvili, Ekaterine ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire

Palazzo, Claudio ; Université de Liège - ULiège > Département de pharmacie

Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques

Piel, Géraldine ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)

Pequeux, Christel ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques

Language :

English

Title :

Use of liposome-encapsulated estetrol for treatment of neonatal hypoxic-ischemic encephalopathy.

Publication date :

15 June 2023

Journal title :

Brain Research

ISSN :

0006-8993

eISSN :

1872-6240

Publisher :

Elsevier B.V., Netherlands

Volume :

1809

Pages :

148369

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://api.elsevier.com/content/article/PII:S0006899323001403?httpAccept=text/xml

Funders :

Région wallonne [BE]
ULiège - University of Liège [BE]
Fonds Léon Fredericq [BE]

Funding text :

We would like to thank the SPW Economie, Emploi, Recherche of the Walloon Region (DG06-WBHealth project Convention n° 1318039) and the Fondation Léon Frédéricq for financial support.

Available on ORBi :

since 26 June 2023

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Bibliography

Abot, A., Fontaine, C., Raymond-Letron, I., Flouriot, G., Adlanmerini, M., Buscato, M., Otto, C., Bergès, H., Laurell, H., Gourdy, P., et al. The AF-1 activation function of estrogen receptor α is necessary and sufficient for uterine epithelial cell proliferation in vivo. Endocrinology 154:6 (2013), 2222–2233.
Agrawal, M., Ajazuddin, Tripathi D.K., Saraf, S., Saraf, S., Antimisiaris, S.G., Mourtas, S., Hammarlund-Udenaes, M., Alexander, A., Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer's disease. J. Control. Release 260 (2017), 61–77.
Al-Azayzih, A., Missaoui, W.N., Cummings, B.S., Somanath, P.R., Liposomal-mediated delivery of the p21 activated kinase-1 (PAK-1) inhibitorIPA-3limits prostate tumor growthin vivo. Nanomedicine 12:5 (2016), 1231–1239.
Alkayed, N.J., Murphy, S.J., Traystman, R.J., Hurn, P.D., Miller, V.M., Neuroprotective effects of female gonadal steroids in reproductively senescent female rats. Stroke 31:1 (2000), 161–168.
Ankarcrona, M., Dypbukt, J.M., Bonfoco, E., Zhivotovsky, B., Orrenius, S., Lipton, S.A., Nicotera, P., Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function. Neuron 15:4 (1995), 961–973.
Arnal, J.F., Valéra, M.C., Payrastre, B., Lenfant, F., Gourdy, P., Structure-function relationship of estrogen receptors in cardiovascular pathophysiological models. Thrombosis Res. Suppl 1:130 (2012), S7–S11.
Arnal, J.F., Lenfant, F., Metivier, R., Flouriot, G., Henrion, D., Adlanmerini, M., Fontaine, C., Gourdy, P., Chambon, P., Katzenellenbogen, B., Katzenellenbogen, J., Membrane and nuclear estrogen receptor alpha actions: from tissue specificity to medical implications. Physiol. Rev. 97:3 (2017), 1045–1087.
Badawi, N., Kurinczuk, J.J., Keogh, J.M., Alessandri, L.M., O'Sullivan, F., Burton, P.R., Pemberton, P.J., Stanley, F.J., Antepartum risk factors for newborn encephalopathy: the Western Australian case-control study. Brit. Med. J. 317:7172 (1998), 1549–1553.
Badawi, N., Kurinczuk, J.J., Keogh, J.M., Alessandri, L.M., O'Sullivan, F., Burton, P.R., Pemberton, P.J., Stanley, F.J., Intrapartum risk factors for newborn encephalopathy: the Western Australian case-control study. Brit. Med. J. 317:7172 (1998), 1554–1558.
Barouk, S., Hintz, T., Li, P., Duffy, A.M., MacLusky, N.J., Scharfman, H.E., 17β-Estradiol Increases Astrocytic Vascular Endothelial Growth Factor (VEGF) in Adult Female Rat Hippocampus. Endocrinology 152:5 (2011), 1745–1751.
Billon-Galés, A., Krust, A., Fontaine, C., Abot, A., Flouriot, G., Toutain, C., Berges, H., Gadeau, A.P., Lenfant, F., Gourdy, P., et al. Activation function 2 (AF2) of estrogen receptor-alpha is equired for the atheroprotective action of estradiol but not to accelerate endothelial healing. Proc. Natl. Acad. Sci. U. S. A. 9:108(32) (2011), 13311–13316.
Brann, D.W., Dhandapani, K., Wakade, C., Mahesh, V.B., Khan, M.M., Neurotrophic and neuroprotective actions of estrogen: basic mechanisms and clinical implications. Steroids 72:5 (2007), 381–405.
Chen, J., Lu, S., Gu, W., Peng, P., Dong, J., Xu, F., Yang, X., Xiong, Z., Yang, X., Characterization of 9-nitrocamptothecin-in-cyclodextrin-in-liposomes modified with transferrin for the treating of tumor. Int. J. Pharmacol. 25:490(1–2) (2015), 219–228.
Cho, J.J., Iannucci, F.A., Fraile, M., Franco, J., Alesius, T.N., Stefano, G.B., The role of the estrogen in neuroprotection: implications for neurodegenerative diseases. Neuro Endocrinol. Lett. 24 (2003), 141–147.
Cipolla, D., Blanchard, J., Gonda, I., Development of liposomal ciprofloxacin to treat lung infections. Pharmaceutics, 8(1), 2016.
Coelingh Bennink, H.J.T., Holinka, C.F., Diczfalusy, E., Estetrol review: profile and potential clinical applications. Climacteric 11:Suppl 1 (2008), 47–58.
Currie, L.J., Harrison, M.B., Trugman, J.M., Bennett, J.P., Wooten, J.F., Postmenopausal estrogen use affects risk for Parkinson disease. Arch. Neurol. 61 (2004), 886–888.
Daraee, H., Etemadi, A., Kouhi, M., Alimirzalu, S., Akbarzadeh, A., Application of liposomes in medicine and drug delivery. Artificial Cells Nanomed. Biotechnol. 44:1 (2016), 381–391.
Deroo, B.J., Korach, K.S., Estrogen receptors and human disease:an unapdate. Arch. Toxicol. 86:10 (2012), 1491–1504.
Edwards, D.A., Azzopardi, D.V., Gunn, A.J., Neonatal Neural Rescue: A Clinical Guide. 2013, Cambridge University Press.
Gallez, A., Palazzo, C., Blacher, S., Tskitishvili, E., Noël, A., Foidart, J.M., Evrard, B., Pequeux, C., Piel, G., Liposomes and drug-in-cyclodextrin-in-liposomes formulations encapsulating 17β-estradiol: An innovative drug delivery system that prevents the activation of the membrane-initiated steroid signaling (MISS) of estrogen receptor α. Int. J. Pharmaceut., 5(573), 2020, 118861.
Gerard, S., Yost, M., Oligschlager, Y., Sweat, M., Foidart, J.M., Estetrol, a Natural Estrogen with Selective Tissue activity (NEST). J. Sexual Med. 19:3 (2022), S24–S25.
Gluckman, P.D., Wyatt, J.S., Azzopardi, D., Ballard, R., Edwards, A.D., Ferriero, D.M., Polin, R.A., Robertson, C.M., Thoresen, M., Whitelaw, A., et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 365:9460 (2005), 663–670.
Gold, S.M., Voskuhl, R.R., Estrogen treatment in multiple sclerosis. 286(1–2) J. Neurol. Sci. 15 (2009), 99–103.
Gonzalez, M., Cabrera-Socorro, A., Perez-Garcia, C.G., Fraser, J.D., Lopez, F.J., Alonso, R., Meyer, G., Distribution patterns of estrogen receptor alpha and beta in the human cortex and hippocampus during development and adulthood. J. Comp. Neurol. 503 (2007), 790–802.
Grafals-Ruiz, N., Rios-Vicil, C.I., Lozada-delgado, E.L., Quiñones-Díaz, B.I., Noriega-Rivera, R.A., Martínez-Zayas, G., Santana-Rivera, Y., Santiago-Sánchez, G.S., Valiyeva, F., Vivas-Mejía, P.E., Brain Targeted Gold Liposomes Improve RNAi Delivery for Glioblastoma 15 (2020), 809–2828.
Graham, E.M., Ruis, K.A., Hartman, A.L., Northington, F.J., Fox, H.E., A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am. J. Obstetr. Gynecol. 199:6 (2008), 587–595.
Hayward, J.N., Baker, M.A., A comparative study of the role of the cerebral arterial blood in the regulation of brain temperature in five mammals. Brain Res. 16:2 (1969), 417–440 (2008).
Heger, Z., Gumulec, J., Cernei, N., Tmejova, K., Kopel, P., Balvan, J., Masarik, M., Zitka, O., Beklova, M., Adam, V., et al. 17β-estradiol-containing liposomes as a novel delivery system for the antisense therapy of ER-positive breast cancer: An in vitro study on the MCF-7 cell line. Oncol. Rep. 33:2 (2015), 921–929.
Henderson, V.W., Benke, K.S., Green, R.C., Cupples, L.A., Farrer, L.A., MIRAGE study Group, Postmenopausal hormone therapy and Alzheimer's disease risk: interaction with age. J. Neurol. Neurosurg. Psychiatry 76 (2005), 103–105.
Hirano, S., Furutama, D., Hanafusa, T., Physiologically high concentrations of 17beta-estradiol enhance NF-kappaB activity in human T cells. Am. J. Physiol. – Regul. Integr. Comp. Physiol. 292:4 (2007), R1465–R1471.
Hoehn, T., Hansmann, G., Bührer, C., Simbruner, G., Gunn, A.J., Yager, J., Levene, M., Hamrick, S.E., Shankaran, S., Thoresen, M., Therapeutic hypothermia in neonates. Review of current clinical data, ILCOR recommendations and suggestions for implementation in neonatal intensive care units. Resuscitation 78 (2008), 7–12.
Holinka, C.F., Diczfalusy, E., Coeling Bennink, H.J.T.C., Estetrol: a unique steroid in human pregnancy. J. Steroid Biochem. Mol. Biol. 110:1–2 (2008), 138–143.
Kolesnichenko, L.S., Kulinsky, V.I., Sotnikova, G.V., Kovten, V.Y., Influence of changes in glutathione concentration on body temperature and tolerance to cerebral ischemia. Biochemistry (Moscow) 68:5 (2003), 534–540.
Krause, D.N., Duckles, S.P., Pelligrino, D.A., Influence of sex steroid hormones on cerebrovascular function. J. Appl. Physiol. 101:4 (2006), 1252–1261.
Kuan, C.Y., Roth, K.A., Flavell, R.A., Rakic, P., Mechanisms of programmed cell death in the developing brain. Trends Neurosci. 23:7 (2000), 291–297.
Lasic, D.D., Frederik, P.M., Stuart, M.C., Barenholz, Y., McIntosh, T.J., Gelation of liposome interior. A novel method for drug encapsulation. FEBS Lett. 312 (1992), 255–258.
Lee, H.S., Han, J., Baim, H.J., Kim, K.W., Brain angiogenesis in developmental and pathological processes: regulation, molecular and cellular communication at the neurovascular interface. FEBS J. 276:17 (2009), 4622–4635.
Mc Carty, M.M., Estradiol and the Developing Brain. Physiol. Rev. 88:1 (2008), 91–124.
Nardo, L., Re, F., Brioschi, S., Cazzaniga, E., Orlando, A., Minniti, S., Lamperti, M., Gregori, M., Cassina, V., Brogioli, D., Salerno, D., Mantegazza F (2016) Fluorimetric detection of the earliest events in amyloid beta oligomerization and its inhibition by pharmacologically active liposomes. Biochim. Biophys. Acta 4 (1860), 746–756.
Ochi, A., Shibata, S., Mori, K., Sato, T., Sunamoto, J., Targeting chemotherapy of brain tumor using liposome encapsulated cisplatin. Part 2. Pullulan anchored liposomes to target brain tumor. Drug Deliv. Syst. 5 (1990), 261–271.
Palazzo, C., Laloy, J., Delvigne, A.S., Nys, G., Fillet, M., Dogne, J.M., Pequeux, C., Foidart, J.M., Evrard, B., Piel, G., Development of injectable liposomes and drug-in-cyclodextrin-in-liposome formulations encapsulating estetrol to prevent cerebral ischemia of premature babies. Eur. J. Pharmaceut. Sci. 15:127 (2019), 52–59.
Paxinos, G., Watson, C., The rat brain in stereotaxic coordinates. 6th ed., 2007, Elsevier Inc.
Quesada, A., Micevych, P.E., Estrogen interacts with the IGF-1 system to protect nigrostriatal dopamine and maintain motoric behavior after 6-hydroxdopamine lesions. J. Neurosci. Res. 75:1 (2004), 107–116.
Reddy, B.S., Banerjee, R., 17Beta-estradiol-associated stealth-liposomal delivery of anticancer gene to breast cancer cells. Angewandte Chemie International Edition in English, 21(44(41)), 2005, 6723.
Samantaray, S., Matzelle, D.D., Ray, S.K., Banik, N.L., Physiological low dose of estrogen-protected neurons in experimental spinal cord injury. Ann. New York Acad. Sci. 1199 (2010), 86–89.
Shankaran, S., Laptook, A.R., Ehrenkranz, R.A., Tyson, J.E., McDonald, S.A., Donovan, E.F., Fanaroff, A.A., Poole, W.K., Wright, L.L., Higgins, R.D., et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. New Engl. J. Med. 353:15 (2005), 1574–1584.
Soni, V., Kohli, D.V., Jain, S.K., Transferrin-conjugated liposomal system for improved delivery of 5-fluorouracil to brain. J. Drug Target. 16:1 (2008), 73–78.
Suzuki, S., Brown, C.M., Wise, P.M., Neuroprotective effects of estrogens following ischemic stroke. Front. Neuroendocrinol. 30 (2009), 201–211.
Thoresen, M., Whitelaw, A., Therapeutic hypothermia for hypoxic-ischaemic encephalopathy in the newborn infant. Curr. Opin. Neurol. 18:2 (2005), 111–116.
Tskitishvili E & Foidart JM. (2019). Estetrol and Its Effects on the Damaged Brain. In the Sex Steroids' Effects on Brain, Heart and Vessels (Volume 6: Frontiers in Gynecological Endocrinology), pp-43-91. Eds RD Brinton, AR Genazzani, T Simoncini & JC Stevenson. Springer Publishing.
Tskitishvili, E., Nisolle, M., Munaut, C., Pequeux, C., Gerard, C., Noel, A., Foidart, J.M., Estetrol attenuates neonatal hypoxic-ischemic brain injury. Experiment. Neurol. 261 (2014), 298–307.
Tskitishvili, E., Pequeux, C., Munaut, C., Viellevoye, R., Nisolle, M., Noël, A., Foidart, J.M., Use of estetrol with other steroids for attenuation of neonatal hypoxic-ischemic brain injury: to combine or not to combine?. Oncotarget 7:23 (2016), 33722–33743.
Tskitishvili, E., Pequeux, C., Munaut, C., Viellevoye, R., Nisolle, M., Noël, A., Foidart, J.M., Estrogen receptors and estetrol-dependent neuroprotective actions: a pilot study. J. Endocrinol. 232:1 (2017), 85–95.
Vannucci, R.C., Vannucci, S.J., Perinatal hypoxic-ischemic brain damage: evolution of an animal model. Dev. Neurosci. 27:2–4 (2005), 81–86.
Visser, M., Foidart, J.-M., Coelingh Bennink, H.J.T., In vitro effects of estetrol on receptor binding, drug targets and human liver cell metabolism. Climacteric (Suppl) 1:11 (2008), 64–68.
Wang, Z.Y., Gopalkrishnashetty Sreenicasmurthy, S., Song, J.X., Liu, J.Y., Li, M., Strategies for brain-targeting liposomal delivery of small hydrophobic molecules in the treatment of neurodegenerative diseases. Drug Discov. Today 24:2 (2019), 595–605.
Wrotek, S., Sobocinska, J., Kozlowski, H.M., Pawlikowska, M., Jędrzejewski, T., Dzialuk, A., New Insights into the Role of Glutathione in the Mechanism of Fever. Int. J. Mol. Sci., 21(4), 2020, 1393.
Zaidi, A.U., D'Sa-Eipper, C., Brenner, J., Kuida, K., Zheng, T.S., Flavell, R.A., Rakic, P., Roth, K.A., Bcl-X(L)-caspase-9 interactions in the developing nervous system: evidence for multiple death pathways. J. Neurosci. 21:1 (2001), 169–175.
Zanelli A. http://emedicine.medscape.com/article/973501-overview?src=refgatesrc1#a5 updated 18 Jul 2018.