Publications of Brigitte Evrard
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See detailInfluence of Composition and Spray-Drying Process Parameters on Carrier-Free DPI Properties and Behaviors in the Lung: A review
Lechanteur, Anna ULiege; Evrard, Brigitte ULiege

in Pharmaceutics (2020)

Although dry powder inhalers (DPIs) have attracted great interest compared to nebulizers and metered-dose inhalers (MDIs), drug deposition in the deep lung is still insufficient to enhance therapeutic ... [more ▼]

Although dry powder inhalers (DPIs) have attracted great interest compared to nebulizers and metered-dose inhalers (MDIs), drug deposition in the deep lung is still insufficient to enhance therapeutic activity. Indeed, it is estimated that only 10%–15% of the drug reaches the deep lung while 20% of the drug is lost in the oropharyngeal sphere and 65% is not released from the carrier. The potentiality of the powders to disperse in the air during the patient’s inhalation, the aerosolization, should be optimized. To do so, new strategies, in addition to classical lactose-carrier, have emerged. The lung deposition of carrier-free particles, mainly produced by spray drying, is higher due to non-interparticulate forces between the carrier and drug, as well as better powder uniformity and aerosolization. Moreover, the association of two or three active ingredients within the same powder seems easier. This review is focused on a new type of carrier-free particles which are characterized by a sugar-based core encompassed by a corrugated shell layer produced by spray drying. All excipients used to produce such particles are dissected and their physico-chemical properties (Péclet number, glass transition temperature) are put in relation with the lung deposition ability of powders. The importance of spray-drying parameters on powders’ properties and behaviors is also evaluated. Special attention is given to the relation between the morphology (characterized by a corrugated surface) and lung deposition performance. The understanding of the closed relation between particle material composition and spray-drying process parameters, impacting the final powder properties, could help in the development of promising DPI systems suitable for local or systemic drug delivery. [less ▲]

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See detailA quality by design approach for liposomes production by innovative method using supercritical fluids: which parameters use to obtain good physicochemical characteristics?
Penoy, Noémie ULiege; Avohou, Tonakpon Hermane ULiege; Lebrun, Pierre ULiege et al

Scientific conference (2019, December 11)

Liposomes are nanoparticles made of phospholipids, able to encapsulate many active molecules, protecting and transporting them in a targeted way. Liposomes are thus widely studied as vectors of numerous ... [more ▼]

Liposomes are nanoparticles made of phospholipids, able to encapsulate many active molecules, protecting and transporting them in a targeted way. Liposomes are thus widely studied as vectors of numerous active molecules, improving their therapeutic window. However, the usual production methods at the laboratory scale have many disadvantages and are generally difficult to transfer to the industrial scale under GMP conditions [1], [2]. Supercritical fluids are increasingly used in the pharmaceutical industry. One of the pharmaceutical applications of supercritical fluids is the production of particles. For the liposomes production, the use of supercritical CO2 as a dispersing agent has been preferred because of the total absence of organic solvent. Since this process involves many parameters such as pressure, temperature, stirring speed, lipid concentration, volume and contact time, a quality by design approach was used in order to determine the influence of each parameters on the physicochemical properties of liposomes such as the size and the polydispersity. These experimental analyses helped us to find two production areas. These conditions were validated with five different liposome formulations regarding the size and polydispersity expectations. We will now focus on the impact of each parameter on the physicochemical properties of liposomes but also their impact on the integrity of the phospholipids used. [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

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 detailPromoting vaginal distribution of two active siRNA-complexed in liposomes for cervical cancer treatment
Lechanteur, Anna ULiege; Furst, Tania; Delvenne, Philippe ULiege et al

Conference (2017, December 07)

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See detailPromoting vaginal distribution of two active siRNA-complexed in liposomes for cervical cancer treatment
Lechanteur, Anna ULiege; Furst, Tania; Delvenne, Philippe ULiege et al

Conference (2017, December 05)

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See detailInterest of cylodextrins in spray-dried microparticles formulation for sustained pulmonary delivery of budesonide
Bigazzi, William ULiege; Dufour, Gilles; De Tullio, Pascal ULiege et al

Poster (2017, June)

The present study aim at developing cyclodextrin-based spray-dried microparticles containing a corticosteroid (budesonide) with an efficient lung delivery and efficacy. Complexation between budesonide and ... [more ▼]

The present study aim at developing cyclodextrin-based spray-dried microparticles containing a corticosteroid (budesonide) with an efficient lung delivery and efficacy. Complexation between budesonide and hydroxypropyl-beta-cyclodextrin (HPBCD) has been investigated and production of spray-dried powder was optimized based on a design of experiments. Wrinkled particles associated with a low bulk density and improved respirable fraction in comparison to a marketed product were obtained. An in vitro test showed that HPBCD is able to decrease the permeability of budesonide across the bronchial epithelium by a sustained release effect. In conclusion, this work reports that the use of cyclodextrin in the formulation of dry powder for inhalation is of a double interest as it both improves respirable fraction and lung residence time of budesonide. [less ▲]

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See detailPromoting vaginal distribution of two active siRNA-complexed in liposomes for cervical cancer treatment
Lechanteur, Anna ULiege; Furst Tania; Evrard, Brigitte ULiege et al

Conference (2017, April 25)

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See detailChanges in biophysical membrane properties induced by the Budesonide/ Hydroxy-β-cyclodextrin complex
dos Santos, Andreia; Bayiha, Jules; Dufour, Gilles et al

in Biochimica et Biophysica Acta. Biomembranes (2017)

Budesonide (BUD), a poorly soluble anti-inflammatory drug, is used to treat patients suffering from asthma and COPD (Chronic Obstructive Pulmonary Disease). Hydroxypropyl-β-cyclodextrin (HPβCD), a ... [more ▼]

Budesonide (BUD), a poorly soluble anti-inflammatory drug, is used to treat patients suffering from asthma and COPD (Chronic Obstructive Pulmonary Disease). Hydroxypropyl-β-cyclodextrin (HPβCD), a biocompatible cyclodextrin known to interact with cholesterol, is used as a drug-solubilizing agent in pharmaceutical formulations. Budesonide administered as an inclusion complex within HPβCD (BUD:HPβCD) required a quarter of the nominal dose of the suspension formulation and significantly reduced neutrophil induced inflammation in a COPD mouse model exceeding the effect of each molecule administered individually. This suggests the role of lipid domains enriched in cholesterol for inflammatory signaling activation. In this context, we investigated the effect of BUD:HPβCD on the biophysical properties of membrane lipids. On cellular models (A549, lung epithelial cells), BUD:HPβCD extracted cholesterol similarly to HPβCD. On large unilamellar vesicles (LUVs), by using the fluorescent probes diphenylhexatriene (DPH) and calcein, we demonstrated an increase in membrane fluidity and permeability induced by BUD:HPβCD in vesicles containing cholesterol. On giant unilamellar vesicles (GUVs) and lipid monolayers, BUD:HPβCD induced the disruption of cholesterol-enriched raft-like liquid ordered domains as well as changes in lipid packing and lipid desorption from the cholesterol monolayers, respectively. Except for membrane fluidity, all these effects were enhanced when HPβCD was complexed with budesonide as compared with HPβCD. Since cholesterol-enriched domains have been linked to membrane signaling including pathways involved in inflammation processes, we hypothesized the effects of BUD:HPβCD could be partly mediated by changes in the biophysical properties of cholesterol-enriched domains. [less ▲]

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See detailIn vitro and in vivo evaluation of an optimized fenofibrate lipid based solid dispersion produced by a PGSS process
Pestieau, Aude ULiege; Lebrun, Sonia; Cahay, Bernard et al

Poster (2015, October 28)

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See detailIn vitro and in vivo evaluation of an optimized fenofibrate lipid based solid dispersion produced by a PGSS process
Pestieau, Aude ULiege; Lebrun, Sonia; Cahay, Bernard et al

Conference (2015, October 28)

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See detailDevelopment and optimization of pegylated lipoplexes for vaginal application
Lechanteur, Anna ULiege; Furst, Tania ULiege; Kanber, Erdem et al

Conference (2014, October 04)

Detailed reference viewed: 38 (8 ULiège)
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See detailPolyplex based on polycarbonate polymesr for an efficient delivery of an anti-angiogenic siRNA
Frère, Antoine ULiege; Tempelaar, Sarah; Peixoto, Paul ULiege et al

Conference (2014, August 28)

Detailed reference viewed: 33 (12 ULiège)