References of "Evrard, Brigitte"
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See detailOzone-primed neutrophils promote early steps of tumor cell metastasis to lungs by enhancing their NET production
Rocks, Natacha ULiege; Vanwinge, Céline ULiege; Radermecker, Coraline ULiege et al

in Thorax (2019), 0

Air pollution, including particulates and gazes such as ozone (O3), is detrimental for patient’s health and has repeatedly been correlated to increased morbidity and mortality in industrialized countries ... [more ▼]

Air pollution, including particulates and gazes such as ozone (O3), is detrimental for patient’s health and has repeatedly been correlated to increased morbidity and mortality in industrialized countries. Although studies have described a link between ambient particulate matter and increased lung cancer morbidity, no direct relation has yet been established between O3 exposure and metastatic dissemination to lungs. [less ▲]

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See detailMesoporous silica impregnation using supercritical carbon dioxide: is the solubility in the supercritical fluid a critical parameter?
Koch, Nathan ULiege; Jennotte, Olivier ULiege; Rocks, Natacha ULiege et al

Conference (2019, May 20)

Recently, mesoporous silica (MS) has been used as a material able to maintain amorphous state of active pharmaceutical ingredients (APIs) due to appropriate pore size and pore morphologies. Among the ... [more ▼]

Recently, mesoporous silica (MS) has been used as a material able to maintain amorphous state of active pharmaceutical ingredients (APIs) due to appropriate pore size and pore morphologies. Among the impregnation methods of MS, techniques using supercritical carbon dioxide (sc-CO2) are promising tools since they provide many advantages, such as the ability to produce a final medicine without any residual toxic material. Solubility of the API in sc-CO2 is reported as one of the most critical parameters, which usually limits its use in drug formulation. Most of APIs have a poor solubility in sc-CO2 and the use of organic solvents is often required1,2. The goal of this study is to evaluate the feasibility of using sc-CO2 techniques for the impregnation of MS by APIs insoluble in sc-CO2. To do so, fenofibrate (FF) is used as model drug since by changing pressure and temperature conditions of the equipment, FF can be either soluble in sc-CO2 or not soluble but molten in the supercritical phase3. FF-MS complexes were produced by four different methods. Physical mixture (PM) composed of FF (70%, 50%, 43% and 41%) and MS were produced using a mixer during 15 minutes. Fusion at atmospheric pressure inclusion was performed in a water bath by keeping PM at a temperature above the fenofibrate melting point during 1h. Supercritical method with dissolved FF was performed by placing PM in a high pressure reactor for 1 hour under supercritical conditions (40°C and minimum 140 bars) leading to the dissolution of FF in sc-CO2 while supercritical method with melted FF was perfomed under supercritical conditions (60°C and 90 bars) leading to the melting but not to the dissolution of FF in sc-CO2. FF-MS complexes were characterized in terms of drug loading by high performance liquid chromatography, in terms of crystallinity by differential scanning calorimetry and in terms of dissolution profile by an appropriate in vitro dissolution test. We have shown that the use of sc-CO2 as fusion medium allows to work with lower temperature and an increased drug loading and homogeneity in comparison with classical melting inclusion methods. FF-MS formulations produced with sc-CO2 as fusion medium give similar crystallinity and dissolution results compare to those produced with supercritical fluids as solvent. Through this study, we show new possibilities of using sc-CO2 for APIs insoluble in this fluid. [less ▲]

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See detailDevelopment of new manufacturing processes for amorphous solid dispersions
Jennotte, Olivier ULiege; Koch, Nathan ULiege; Rocks, Natacha ULiege et al

Conference (2019, May 20)

Use of the hot-melt extrusion form amorphous solid dispersions of atorvastatin calcium trihydrate with a selection of three polymers in order to enhance its aqueous solubility

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See detailHot melt extrusion as a solvent-free technique for the formation of a polymeric amorphous solid dispersion of atorvastatin
Jennotte, Olivier ULiege; Koch, Nathan ULiege; Collard, Laurence ULiege et al

Poster (2019, March 26)

Hot-melt extrusion as a solvent-free technique for the enhancement of BCSII molecules.

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See detailAssessment of drug skin tolerance in Africans using chromameter
Sounouvou, Axel Gérald Hope Tognidé ULiege; Quetin-Leclercq, Joëlle; Piel, Géraldine ULiege et al

Poster (2019, March 26)

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See detailEnhancement of skin penetration of lipi-based nanocarriers
Bellefroid, Coralie ULiege; Lechanteur, Anna ULiege; Evrard, Brigitte ULiege et al

Conference (2019, March 25)

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See detailLipid gene nanocarriers for the treatment of skin diseases: current state-of-the-art
Bellefroid, Coralie ULiege; Lechanteur, Anna ULiege; Evrard, Brigitte ULiege et al

in European Journal of Pharmaceutics and Biopharmaceutics (2019)

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See detailUpdate of the progresses and development prospects of the FEDER project Phare
Emonts, Paul ULiege; Penoy, Noémie ULiege; Rocks, Natacha ULiege et al

Scientific conference (2019, January 19)

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See detailDevelopment 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 Sophie et al

in European Journal of Pharmaceutical Sciences (2019), 9(127), 52-59

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 ... [more ▼]

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. [less ▲]

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See detailEnhancement of skin penetration of lipid-based nanocarriers
Bellefroid, Coralie ULiege; Lechanteur, Anna ULiege; Evrard, Brigitte ULiege et al

Scientific conference (2018, December 19)

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See detailHot melt extrusion as a solvent-free technique for the formation of a polymeric amorphous solid dispersion of atorvastatin
Jennotte, Olivier ULiege; Koch, Nathan ULiege; Collard, Laurence ULiege et al

Scientific conference (2018, December 19)

Water-solubility enhancement of atorvastatin using the hot melt extrusion for the production of a polymeric amorphous solid dispersion

Detailed reference viewed: 42 (16 ULiège)
See detailLiposome production by innovative method using supercritical fluids
Penoy, Noémie ULiege; Bigazzi, William ULiege; Piel, Géraldine ULiege et al

Scientific conference (2018, December 19)

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See detailCationic Liposomes Carrying siRNA: Impact of Lipid Composition on Physicochemical Properties, Cytotoxicity and Endosomal Escape
Lechanteur, Anna ULiege; Sanna, Vincent; Duchemin, Amandine ULiege et al

Conference (2018, August)

In recent year, cationic liposomes have gained a lot of attention for siRNA delivery using different local routes of administration as the vaginal [1] or the pulmonary routes. However, lipoplexes have to ... [more ▼]

In recent year, cationic liposomes have gained a lot of attention for siRNA delivery using different local routes of administration as the vaginal [1] or the pulmonary routes. However, lipoplexes have to face several biological and intracellular barriers before releasing the genetic cargo. In this study, we focus our effort on intracellular barriers and more specifically on endosomal escape and cytosolic delivery of siRNA as well as on the cytotoxicity due to cationic lipids. Indeed, we have previously demonstrated that the surface charge of liposomes composed of the cationic lipid DOTAP is correlated to the induction of cytotoxicity [2]. In the present study, we have investigated the impact of different cationic lipids and co-lipids on the cytotoxicity and also on the endosomal escape of siRNA by flow cytometry, qRT-PCR and Western Blot assays [3]. To address these issues, we developed four liposomal formulations composed of two different cationic lipids (DOTAP and DC-Cholesterol) and different ratio of co-lipids (cholesterol and DOPE). Formulations were DOTAP/Cholesterol/DOPE 1/0.75/0.5, DOTAP/Cholesterol/DOPE 1/0.5/0.5, DOTAP/DOPE 1/1 and DC-Cholesterol/DOPE 1/1. Each type of liposomes were complexed to siRNA at six different N/P molar ratios and physico-chemical properties were characterized in terms of Z-average size, Zeta potential and complexation efficiency by gel retardation assay. Consequently, three N/P ratios (2.5, 5 and 10) were selected for in vitro experiments on A549 cells. First, we studied the cell viability of A549 cells treated during 24 h with liposomes complexed to inactive siRNA at different N/P molar ratios at siRNA concentrations of 40 and 100 nM. We have shown that the cytotoxicity is influenced by the N/P ratio, the concentration of cationic lipid as well as the nature of the cationic lipid. Secondly, the cellular uptake were evaluated by flow cytometry using the dry Trypan Blue® to quench the external fluorescence. Despite the fact the transfection rate were not significantly different, the mRNA knock-down efficiency were not similar between formulations. Liposomes containing 50% of DOPE induced a mRNA silencing of around 80% as well as the protein knock-down. This study allowed to highlight crucial parameters in order to develop lipoplexes which are safe and induce an efficient intracytoplasmic release of siRNA. Acknowledgments: The authors thank the Belgium National Fund for Scientific Research (FNRS, http://www.frs-fnrs.be) –Télévie for financial support and the Giga Cell Imaging and Flow Cytometry Platform for their collaboration. Anna Lechanteur is a FNRS-Télévie post-doctoral researcher. Amandine Duchemin is a FRIA FNRS Fellow. Denis Mottet is a FNRS Research Associate. References: 1. Lechanteur, A., Furst, T. Delvenne, P. et al., Promoting vaginal distribution of E7 and MCL-1 siRNA-silencing nanoparticles for cervical cancer treatment Molecular Pharmaceutics, 2017. 14: p. 1706-1717. 2. Lechanteur, A., Furst, T. Evrard, B. et al., PEGylation of lipoplexes: The right balance between cytotoxicity and siRNA effectiveness. Eur J Pharm Sci, 2016. 93: p. 493-503. 3. Lechanteur, A., Sanna, V. Duchemin, A. et al., Cationic Liposomes Carrying siRNA: Impact of Lipid Composition on Physicochemical Properties, Cytotoxicity and Endosomal Escape. Nanomaterials (Basel), 2018. 8(270): p. 1-12. [less ▲]

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See detailAssessment of skin penetration of classical and deformable liposomes
Bellefroid, Coralie ULiege; Lechanteur, Anna ULiege; Evrard, Brigitte ULiege et al

Conference (2018, July 12)

The skin is the largest organ of the human body representing an alternative route of administration by providing an easy and pain-free drug delivery option. Cutaneous drug delivery is not associated with ... [more ▼]

The skin is the largest organ of the human body representing an alternative route of administration by providing an easy and pain-free drug delivery option. Cutaneous drug delivery is not associated with a significant drug loss compared to systemic administration due to low enzymatic degradation and a negligible clearance. Moreover, the systemic toxicity resulting from cutaneous application is limited and side effects are easy to observe and to handle [1]. Thanks to these advantages there is a great interest in using the skin as a route of administration. Besides physical and active methods involving the disruption of the stratum corneum (SC) to increase the penetration of drugs in the underlying layers, passive methods using of non-viral vectors, particularly lipid-based nanovectors, is one of the most attractive method [2]. They were developed to increase topical macromolecules penetration through the SC barrier and to promote the intracellular delivery of large molecules such as nucleic acids. However, it has become obvious that conventional liposomes do not promote the skin penetration without enhancement techniques [3]. The aim of this study is to assess the skin penetration of lipid-based nanocarriers according to their composition. The skin penetration of conventional liposomes was compared to the penetration of deformable liposomes with ethanol and/or edge activators (EA). 25% (w/w) of ethanol was added to conventional liposomes (DOTAP/DOPE) to form ethosomes. Sodium Cholate and Tween®80 were used as EA to develop deformable liposomes. Formulations were characterized in terms of size, polydispersity index and surface charge. Ex vivo skin penetration experiment were performed using pig ear skin on Franz cells. In order to visualize the penetration through the skin using confocal microscopy, nanocarriers were fluorescently labeled with a fluorescent lipid (NBD-PC). A kinetic of application was performed (from 3h to 24h) and each condition was done with or without tape stripping. In this study, we showed that all the formulations were not able to penetrate the skin, even for deformable formulations. However, when the SC was removed, formulations containing ethanol allowed penetration into the epidermis. Moreover, the addition of an EA seems to encourage deeper penetration. Acknowledgments: Authors thank the Walloon Region and FEDER for financial supports. References: 1. Zakrewsky, M., S. Kumar, and S. Mitragotri, Nucleic acid delivery into skin for the treatment of skin disease: Proofs-of-concept, potential impact, and remaining challenges. J Control Release, 2015. 219: p. 445-56. 2. Geusens, B., et al., Lipid-mediated gene delivery to the skin. Eur J Pharm Sci, 2011. 43(4): p. 199-211. 3. Sala, M., et al., Lipid nanocarriers as skin drug delivery systems: Properties, mechanisms of skin interactions and medical applications. Int J Pharm, 2018. 535(1-2): p. 1-17. [less ▲]

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See detailCationic Liposomes Carrying siRNA: Impact of Lipid Composition on Physicochemical Properties, Cytotoxicity and Endosomal Escape
Lechanteur, Anna ULiege; Sanna, Vincent; Duchemin, Amandine ULiege et al

in Nanomaterials (2018), 8(5),

Abstract: In recent year, cationic liposomes have gained a lot of attention for siRNA delivery. Despite this, intracellular barriers as endosomal escape and cytosolic delivery of siRNA still represent a ... [more ▼]

Abstract: In recent year, cationic liposomes have gained a lot of attention for siRNA delivery. Despite this, intracellular barriers as endosomal escape and cytosolic delivery of siRNA still represent a challeng, as well as the cytotoxicity due to cationic lipids. To address these issues, we developed four liposomal formulations, composed of two different cationic lipids (DOTAP and DC-Cholesterol) and different ratio of co-lipids (cholesterol and DOPE). The objective is to dissect these impacts on siRNA efficacy and cytotoxicity. Liposomes were complexed to siRNA at six different N/P molar ratios, physico-chemical properties were characterized, and consequently, N/P 2.5, 5 and 10 were selected for in vitro experiments. We have shown that cytotoxicity is influenced by the N/P ratio, the concentration of cationic lipid, as well as the nature of the cationic lipid. For instance, cell viability decreased by 70% with liposomes composed of DOTAP/Cholesterol/DOPE 1/0.75/0.5 at a N/P ratio 10, whereas the same formulation at a N/P ratio of 2.5 was safe. Interestingly, we have observed differences in terms of mRNA knock-down efficiency, whereas the transfection rate was quite similar for each formulation. Liposomes containing 50% of DOPE induced a mRNA silencing of around 80%. This study allowed us to highlight crucial parameters in order to develop lipoplexes which are safe, and which induce an efficient intracytoplasmic release of siRNA. [less ▲]

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See detailCationic Liposomes Carrying siRNA: Impact of Lipid Composition on Physicochemical Properties, Cytotoxicity and Endosomal Escape
Lechanteur, Anna ULiege; Sanna, Vincent; Duchemin, Amandine ULiege et al

in Cationic liposomes carrying siRNA: impact of lipid composition on physicochemical properties, cytotoxicity and endosomal escape (2018, April)

In recent year, cationic liposomes have gained attention for siRNA delivery using different local routes of administration as the vaginal [Lechanteur et al, Mol Pharm.2017] or the pulmonary routes ... [more ▼]

In recent year, cationic liposomes have gained attention for siRNA delivery using different local routes of administration as the vaginal [Lechanteur et al, Mol Pharm.2017] or the pulmonary routes. However, lipoplexes have to face several biological and intracellular barriers before releasing the genetic cargo. In this study, we focus our effort on intracellular barriers and more specifically on endosomal escape and cytosolic delivery of siRNA as well as on the cytotoxicity due to cationic lipids. Indeed, we have previously demonstrated that the surface charge of liposomes composed of the cationic lipid DOTAP is correlated to the induction of cytotoxicity [Lechanteur et al. EJPS.2016]. In the present study, we have investigated the impact of different cationic lipids and co-lipids on the cytotoxicity and also on the endosomal escape of siRNA by flow cytometry, qRT-PCR and Western Blot assays [Lechanteur et al. Nanomat.2018]. To address these issues, we developed four liposomal formulations composed of two different cationic lipids (DOTAP and DC-Cholesterol) and different ratio of co-lipids (cholesterol and DOPE). Formulations were DOTAP/Cholesterol/DOPE 1/0.75/0.5, DOTAP/Cholesterol/DOPE 1/0.5/0.5, DOTAP/DOPE 1/1 and DC-Cholesterol/DOPE 1/1. Each type of liposomes were complexed to siRNA at six different N/P molar ratios and physico-chemical properties were characterized in terms of Z-average size, Zeta potential and complexation efficiency. Consequently, three N/P ratios (2.5, 5 and 10) were selected for in vitro experiments on A549 cells. We studied the cell viability of cells with liposomes complexed to inactive siRNA at different N/P molar ratios at two siRNA concentrations. We have shown that the cytotoxicity is influenced by the N/P ratio, the concentration of cationic lipid as well as the nature of the cationic lipid. The cellular uptake were evaluated using the dye Trypan Blue® to quench the external fluorescence. Despite the fact the transfection rate were not significantly different, the mRNA knock-down efficiency were not similar between formulations. Liposomes containing 50% of DOPE induced a mRNA silencing of around 80% as well as the protein knock-down. This study allowed to highlight crucial parameters in order to develop lipoplexes which are safe and induce an efficient intracytoplasmic release of siRNA. [less ▲]

Detailed reference viewed: 34 (1 ULiège)