Development of injectable liposomes and drug-in-cyclodextrin-in-liposome formulations encapsulating estetrol to prevent cerebral ischemia of premature babies.
Palazzo, Claudio; Laloy, Julie; Delvigne, Anne Sophieet al.
2019 • In European Journal of Pharmaceutical Sciences, 9 (127), p. 52-59
[en] Neonatal Hypoxic-Ischemic Encephalopathy (HIE), a brain disease due to brain hypoxia along with ischemia and reduced cerebral blood flow, is one of the primary reasons of severe injury among babies prematurely born. No efficacy treatment is available to the present day. Estetrol (E4), a major estradiol metabolite, has an important role in the brain development and protection. The aim of this study is to develop new injectable liposome and drug-in-cyclodextrin-in-liposome (DCL) formulations, encapsulating E4 in order to enhance its crossing through the blood-brain barrier (BBB). Liposome and DCL formulations were prepared and were physiochemically characterized. Stability in foetal bovine serum (FBS) was evaluated. LDH and MTS tests on endothelial, neuronal and BBB model cells, as well as hemocompatibility of the nanovectors were performed in vitro. In vitro BBB passage was evaluated using human BBB cell line (hCMEC/D3). All the formulations had average particle size below 150 nm, polydispersity index below 0.10 and ζ potential around + 30 mV. The encapsulation efficacy for liposomes was between 3% and 10% while those of DCL are between 15% and 35%. The effect of liposome and DCL formulations on cell viability and integrity was evaluated. The results showed no toxic effects on all the tested cell lines. Hemocompatibility tests showed no hemolysis, platelet aggregation or effects on coagulation, confirming the possibility of the formulations to be intravenously administrated. BBB passage tests highlighted the capability of the formulations to pass the BBB and reach the brain. Therefore, the formulations are promising drug delivery system to target estrogens to the brain, due to their physiochemical characteristics.
Research center :
CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Palazzo, Claudio ; Université de Liège > Département de pharmacie > Département de pharmacie
Laloy, Julie; Université de Namur - UNamur
Delvigne, Anne Sophie; Université de Namur - UNamur
Nys, Gwenaël ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Fillet, Marianne ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Dogne, Jean Michel; Université de Namur - UNamur
Pequeux, Christel ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques
Evrard, Brigitte ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Piel, Géraldine ; Université de Liège - ULiège > Département de pharmacie > Développement de nanomédicaments
Language :
English
Title :
Development of injectable liposomes and drug-in-cyclodextrin-in-liposome formulations encapsulating estetrol to prevent cerebral ischemia of premature babies.
Publication date :
2019
Journal title :
European Journal of Pharmaceutical Sciences
ISSN :
0928-0987
eISSN :
1879-0720
Publisher :
Elsevier, Netherlands
Volume :
9
Issue :
127
Pages :
52-59
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Estelip
Funders :
DGTRE - Région wallonne. Direction générale des Technologies, de la Recherche et de l'Énergie [BE]
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