References of "Evrard, Brigitte"
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See detailImpregnation of mesoporous silica with poor aqueous soluble molecule using pressurized carbon dioxide: is the solubility in the supercritical and subcritical phase a critical parameter?
Koch, Nathan ULiege; Jennotte, Olivier ULiege; Grignard, Bruno ULiege et al

in European Journal of Pharmaceutical Sciences (2020), 150

Recently, mesoporous silica (MS) has been used as a material able to maintain amorphous state of active compounds and therefore, enhance the oral bioavailability of BCSII drugs. Among impregnation methods ... [more ▼]

Recently, mesoporous silica (MS) has been used as a material able to maintain amorphous state of active compounds and therefore, enhance the oral bioavailability of BCSII drugs. Among impregnation methods of MS, techniques using supercritical carbon dioxide (sc-CO2) are promising tools. Solubility of compounds in sc-CO2 is reported as one of the most critical parameters, which usually limits its use in drug formulation. Indeed, most of compounds have poor solubility in sc-CO2. The aim of this work is to compare different MS and to study alternative processes using pressurized CO2 for insoluble molecule in sc-CO2. By using high pressure reactor, DSC, HPLC and in vitro dissolution tests, the crystallinity and dissolution profiles of MS with different pore size (6.6 nm, 25.0 nm and 2.5 nm) impregnated with fenofibrate (FF) under sc-CO2 were compared to select the most appropriate carrier. Then, the selected MS has been impregnated under supercritical, subcritical and atmospheric conditions. We have shown that the MS pore size of 6.6 nm provides the higher amorphous drug loading capacity as well as the faster and higher drug dissolution. In addition, FF-MS formulations produced with pressurized CO2 as fusion medium, both in subcritical and supercritical conditions; give similar crystallinity and dissolution results compared to those produced with supercritical fluids as solvent. Through this study, we show new possibilities of using CO2 for insoluble compounds in this fluid. [less ▲]

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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 detailLiposomes 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
Gallez, Anne ULiege; Palazzo, Claudio ULiege; Blacher, Silvia ULiege et al

in International Journal of Pharmaceutics (2020), 573

The encapsulation into liposomes of several types of molecules presents the advantages to protect the activity of these molecules and to target specific tissues. Nevertheless, a major obstacle remains the ... [more ▼]

The encapsulation into liposomes of several types of molecules presents the advantages to protect the activity of these molecules and to target specific tissues. Nevertheless, a major obstacle remains the incomplete understanding of nano-bio interactions. Specifically, the impact that inclusion of drug into liposomes or of drug-in-cyclodextrin-in liposomes (DCL) could have on the molecular and cellular mechanism of drug action is largely unknown. As a proof of concept, we evaluated the impact of 17β-estradiol (E2) included into liposomes or DCL on estrogen receptor (ER)α signaling pathways. Indeed, ERα relays the pleiotropic actions of E2 in physiology and pathophysiology through two major pathways: (1) the genomic/nuclear effects associated to the transcriptional activity of the ERα and (2) the rapid/nongenomic/membrane-initiated steroid signaling (MISS) effects related to the induction of fast signaling pathways occurring when ERα is anchored to the plasma membrane. We evidenced that the inclusion of E2 into liposomes (Lipo-E2) or into DCL (DCL-E2) prevented the activation of the rapid/nongenomic/extranuclear/MISS pathway of ERα, while the activation of the genomic/nuclear pathway was maintained. These results support that Lipo-E2 and DCL-E2 could be a useful tool to delineate the complex molecular mechanisms associated to ERα. In conclusion, this study supports the notion that inclusion of drugs into liposomes or DCL could modify some specific pathways of their molecular and cellular mechanisms of action. These results emphasized that attention should be paid to nano-bio interactions induced by the use of nanovectors in medicine. [less ▲]

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See detailThree-dimensional printing technology as a promising tool in bioavailability enhancement of poorly water-soluble molecules: a review
Jennotte, Olivier ULiege; Koch, Nathan ULiege; Lechanteur, Anna ULiege et al

in International Journal of Pharmaceutics (2020)

Poor aqueous solubility of active pharmaceutical ingredients (API) is nowadays a major issue in the pharmaceutical field. The combinatorial chemistry provides more and more API with a great therapeutic ... [more ▼]

Poor aqueous solubility of active pharmaceutical ingredients (API) is nowadays a major issue in the pharmaceutical field. The combinatorial chemistry provides more and more API with a great therapeutic potential, but with a low aqueous solubility. Among the strategies to overcome this drawback, the use of amorphous solid dispersions (ASD), as well as the increase of surface area, is widely used. The three dimensional (3D) printing technologies appear to be innovative tools allowing the construction of any unconventional forms with different composition, structure or infill; especially by using ASD materials. This review aims to deliver notions about the different 3D printing techniques found in the literature to improve aqueous solubility of several API, namely nozzle-based method, inkjet methods and laser-based methods, as well as guide formulator in terms of formulation parameters that have to be optimized to allow the most suitable impression of innovative medicines. [less ▲]

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See detailIn vitro skin penetration enchancement techniques: a combined approach of ethosomes and microneedles
Bellefroid, Coralie ULiege; Lechanteur, Anna ULiege; Evrard, Brigitte ULiege et al

in International Journal of Pharmaceutics (2019), 572

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See detailImprovement water-solubility of ellagic acid for use as an antimalarial drug through oral administration
Nyamba, Isaïe ULiege; Lechanteur, Anna ULiege; Evrard, Brigitte ULiege et al

Poster (2019, December 11)

Ellagic acid (EA) is a polyphenolic compound, classed as a BCS IV drug, having anti-plasmodial activity on plasmodium-infected cell cultures. However, this class of molecules has a low oral ... [more ▼]

Ellagic acid (EA) is a polyphenolic compound, classed as a BCS IV drug, having anti-plasmodial activity on plasmodium-infected cell cultures. However, this class of molecules has a low oral bioavailability. The aim of our study is to increase the aqueous solubility and therefore the bioavailability of EA to allow its use orally as an antimalarial. To achieve this goal, solid dispersions of EA were made using the hot melt extrusion process. For this purpose, a Scamex® twin-screw corotative extruder was used for the production of extrudates from mixtures of EA powders (5% w/w) and polymers (95% w/w). Three polymers were used as Eudragit® EPO, Kollidon VA® 64 and Soluplus®. The release profile of the EA from the extrudates was evaluated in vitro by dissolution tests under non sink conditions in acidic medium (0.1N HCl) and close to neutrality (pH 6.8 phosphate buffer). Eudragit® EPO-based extrudates showed the best release profile of AE with a 94% release rate after 15 min while Kollidon VA® 64 and Soluplus® extrudates showed a dissolution of AE of 38.5% and 30.66%, respectively. The apparent solubility resulting from these release rates corresponded to a respective increase of 62, 25 and 20 times compared to the actual solubility of EA. Moreover, the supersaturated solutions of Eudragit® EPO and Soluplus® were stable for at least 1h30 min. In conclusion, the solid dispersion made of Eudragit® EPO and EA seems appropriated to enhance the oral bioavailability of the drug. [less ▲]

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See detailEffects of supercritical carbon dioxide sterilization conditions on physicochemical characteristics of liposomes
Delma, Kouka Luc ULiege; Semdé, Rasmané; Evrard, Brigitte ULiege et al

Poster (2019, December 11)

Sterility is a requirement for parenteral administration of liposomes. However, conventional sterilization methods of liposomes have limitations. Supercritical Carbon Dioxide (ScCO2) is a promising ... [more ▼]

Sterility is a requirement for parenteral administration of liposomes. However, conventional sterilization methods of liposomes have limitations. Supercritical Carbon Dioxide (ScCO2) is a promising strategy for the sterilization of sensitive products. In this work, the effects of ScCO2 sterilization conditions on physicochemical characteristics of liposomes were investigated using a liposome formulation previously validated in the LPTB. This model formulation contains cholesterol, dimethylaminoethane-carbamoyl hydrochloride (DC-cholesterol), egg phosphatidylcholine (EPC) and distearoylphosphatidylethanolamine (DSPE) PEG2000, and as active drug, apigenin. Liposomes were prepared by thin-film hydration method and the physicochemical characteristics such as pH, particle size, polydispersity index (PDI), zeta potential, amount of encapsulated apigenin and phospholipids concentration were determined before and after submission to the selected ScCO2 sterilization conditions: 70 ° C, 150 bar for 4h (Karajanagi and al, 2011). The results showed a decrease of the pH of the dispersion, the size, the zeta potential of the vesicles and of the amount of encapsulated apigenin. On the contrary, an increase in PDI after treatment with ScCO2 was observed. In spite of changes observed with this liposome formulation under sterilization conditions used in this work, others conditions should be tested in order to maintain the characteristics of the formulations before and after the sterilization process. [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 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. References [1] C. Tikshdeep, A. Sonia, P. Bharat, and C. Abhishek, “Liposome Drug Delivery,” Int. J. Pharm. Chem. Sci., vol. 1, no. 3, pp. 1103–1113, 2012. [2] L. A. Meure, N. R. Foster, and F. Dehghani, “Conventional and Dense Gas Techniques for the Production of Liposomes: A Review,” AAPS PharmSciTech, vol. 9, no. 3, pp. 798–809, 2008. [3] B. S. Sekhon, “Supercritical fluid technology: An overview of pharmaceutical applications,” Int. J. PharmTech Res., vol. 2, no. 1, pp. 810–826, 2010 [less ▲]

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See detailAssessment of the feasibility to develop a fast and easy reproducible 3D bronchial model growing at the air-liquid interface: Which critical culture parameters must be controlled?
Lechanteur, Anna ULiege; Evrard, Brigitte ULiege; Piel, Géraldine ULiege

Poster (2019, December 11)

The discovery and evaluation of new active drugs will be easier thanks to the development of 3D-epithelial model mimicking biological barriers (1). These models closer to in vivo conditions should help to ... [more ▼]

The discovery and evaluation of new active drugs will be easier thanks to the development of 3D-epithelial model mimicking biological barriers (1). These models closer to in vivo conditions should help to speed up the drug development process. Regarding lung administration, despite many studies exploring the development of 2D-model using Calu-3 cells, there are still multiple disparities about experimental methods and a standardization is needed. We investigated the impact of different culture parameters (time, cell densities,…) on the integrity and the morphology of a 2D model (2). Using permeability studies, electron microscopy and immunohistochemistry, we propose an easy and reproducible 2D-model with Calu-3 cells fully differentiated after 14 days of growing at the air-liquid interface. Moreover, based on these results, we went further with a 3D-bronchial model which consists of a collagen matrix, fibroblasts laid under the epithelial layer. We aim to assess the feasibility to develop a 3D cell-based model of the human airway growing at the air-liquid interface. Many parameters which have to be tightly controlled to develop an extracellular matrix equivalent without any shrinking of the gel encompassing alive fibroblasts as well as over epithelial cells have been identified. Overall, this in vitro model is a differentiated pseudo-stratified bronchial mucosa with mucus expression which is the basis for further optimization allowing the screening of pulmonary drugs in terms of permeability, cytotoxicity or particle-mucus interactions. (1) A. Lechanteur, et al. ADDR. 124 (2018) 50–63. (2) A. Lechanteur, et al. EJPB. 144 (2019) 2–10. [less ▲]

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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; Lechanteur, Anna ULiege et al

Conference (2019, December 11)

Hot-melt extrusion for the formation of an amorphous solid dispersion of atorvastatin in order to enhance its aqueous solubility

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See detailPlein gaz : enjeux et perspectives de la valorisation du CO2
Léonard, Grégoire ULiege; Evrard, Brigitte ULiege; Grignard, Bruno ULiege et al

Conference given outside the academic context (2019)

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See detailChromametric assessment of drug skin tolerance: A comparative study between Africans and Caucasians skins
Sounouvou, Axel Gérald Hope Tognidé ULiege; Lechanteur, Anna ULiege; Quetin-Leclercq, Joëlle et al

in Skin Research and Technology (2019)

Background/Aims: During dermatological forms development, one of the simplest non-invasive techniques used to evaluate cutaneous tolerance of formulations is to monitor the color changes using a ... [more ▼]

Background/Aims: During dermatological forms development, one of the simplest non-invasive techniques used to evaluate cutaneous tolerance of formulations is to monitor the color changes using a tristimulus chromameter. Most published tolerance studies involving chromametric measurements are performed on Caucasian subjects. However, in the context of drug formulation for African-type populations, it is not always relevant to transpose tolerance results obtained on Caucasians populations to African-type ones due to histological ethnic differences of the skin. The goal of this work was to assess whether tristimulus chromameter can be used to highlight color variations following the application of dermatological topics on black skin in order to validate skin tolerance studies made on African-type subjects. Materials and Methods: After application of two commercial creams with opposite side effects (skin irritation and skin blanching) in both Africans and Caucasians populations, color variations were evaluated using a tristimulus chromameter in L*a*b* color system and compared between both populations. L* indicating color brightness, a* represents green and red directions and b* represents blue and yellow directions. Results: While skin irritation resulted in a significant increase of a* parameter in both studied populations, the skin blanching resulted in a decrease of a* associated with an increase of L*. Conclusion: We established that tristimulus chromameter can be used to achieve in vivo skin tolerance study of dermatologic formulations in Africans despite their dark skin even though it appeared less sensitive. This study can speed up the development of dermatological forms dedicated to Africans and/or Caucasians subjects. [less ▲]

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See detailEtude de l’influence des conditions de stérilisation par le dioxyde de carbone en phase supercritique (CO2Sc) sur les caractéristiques physicochimiques de liposomes
Delma, Kouka Luc ULiege; Semdé, Rasmané; Evrard, Brigitte ULiege et al

Conference (2019, November 27)

Sterility is a requirement for parenteral administration of liposomes. However, conventional sterilization methods of liposomes have limitations. Supercritical Carbon Dioxide (ScCO2) is a promising ... [more ▼]

Sterility is a requirement for parenteral administration of liposomes. However, conventional sterilization methods of liposomes have limitations. Supercritical Carbon Dioxide (ScCO2) is a promising strategy for the sterilization of sensitive products. In this work, the effects of ScCO2 sterilization conditions on physicochemical characteristics of liposomes were investigated using a liposome formulation previously validated in the LPTB. This model formulation contains cholesterol, dimethylaminoethane-carbamoyl hydrochloride (DC-cholesterol), egg phosphatidylcholine (EPC) and distearoylphosphatidylethanolamine (DSPE) PEG2000, and as active drug, apigenin. Liposomes were prepared by thin-film hydration method and the physicochemical characteristics such as pH, particle size, polydispersity index (PDI), zeta potential, amount of encapsulated apigenin and phospholipids concentration were determined before and after submission to the selected ScCO2 sterilization conditions: 70 ° C, 150 bar for 4h (Karajanagi and al, 2011). The results showed a decrease of the pH of the dispersion, the size, the zeta potential of the vesicles and of the amount of encapsulated apigenin. On the contrary, an increase in PDI after treatment with ScCO2 was observed. In spite of changes observed with this liposome formulation under sterilization conditions used in this work, others conditions should be tested in order to maintain the characteristics of the formulations before and after the sterilization process. [less ▲]

Detailed reference viewed: 17 (1 ULiège)
See detailEtude de l’influence des conditions de stérilisation par le dioxyde de carbone en phase supercritique (CO2Sc) sur les caractéristiques physicochimiques de liposomes
Delma, Kouka Luc ULiege; Semdé, Rasmané; Evrard, Brigitte ULiege et al

Poster (2019, November)

Sterility is a requirement for parenteral administration of liposomes. However, conventional sterilization methods of liposomes have limitations. Supercritical Carbon Dioxide (ScCO2) is a promising ... [more ▼]

Sterility is a requirement for parenteral administration of liposomes. However, conventional sterilization methods of liposomes have limitations. Supercritical Carbon Dioxide (ScCO2) is a promising strategy for the sterilization of sensitive products. In this work, the effects of ScCO2 sterilization conditions on physicochemical characteristics of liposomes were investigated using a liposome formulation previously validated in the LPTB. This model formulation contains cholesterol, dimethylaminoethane-carbamoyl hydrochloride (DC-cholesterol), egg phosphatidylcholine (EPC) and distearoylphosphatidylethanolamine (DSPE) PEG2000, and as active drug, apigenin. Liposomes were prepared by thin-film hydration method and the physicochemical characteristics such as pH, particle size, polydispersity index (PDI), zeta potential, amount of encapsulated apigenin and phospholipids concentration were determined before and after submission to the selected ScCO2 sterilization conditions: 70 ° C, 150 bar for 4h (Karajanagi and al, 2011). The results showed a decrease of the pH of the dispersion, the size, the zeta potential of the vesicles and of the amount of encapsulated apigenin. On the contrary, an increase in PDI after treatment with ScCO2 was observed. In spite of changes observed with this liposome formulation under sterilization conditions used in this work, others conditions should be tested in order to maintain the characteristics of the formulations before and after the sterilization process. [less ▲]

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See detailAssessment of the feasibility to develop a fast and easy reproducible 3D bronchial model growing at the air-liquid interface: Which critical culture parameters must be controlled?
Lechanteur, Anna ULiege; Evrard, Brigitte ULiege; Piel, Géraldine ULiege

in European Journal of Pharmaceutics and Biopharmaceutics (2019)

The discovery and evaluation of new active drugs will be easier thanks to the development of 3D-epithelial model mimicking biological barriers. These models close to in vivo conditions should help to ... [more ▼]

The discovery and evaluation of new active drugs will be easier thanks to the development of 3D-epithelial model mimicking biological barriers. These models close to in vivo conditions should help to speed up the drug development process while reducing in vivo animal testing. Regarding lung administration, despite many studies exploring the development of 2D-model using Calu-3 cells, there are still multiple disparities about experimental methods and a standardization is needed. We investigated the impact of different culture parameters (time, cell densities, Transwell™ membrane pore sizes or the culture media) on the integrity and the morphology of a 2D model. Using permeability studies, electron microscopy and immunohistochemistry, we propose an easy and reproducible 2D-model with Calu-3 cells fully differentiated after 14 days of growing at the air-liquid interface. Moreover, based on these results, we went further with a 3D-bronchial model which consists of a collagen matrix, fibroblasts laid under the epithelial layer. We aim to assess the feasibility to develop a 3D cell-based model of the human airway growing at the air-liquid interface. Many parameters which have to be tightly controlled to develop an extracellular matrix equivalent without any shrinking of the gel encompassing alive fibroblasts as well as over epithelial cells have been identified. Overall, this in vitro model is a differentiated pseudo-stratified bronchial mucosa with mucus expression which is the basis for further optimization allowing the screening of pulmonary drugs in terms of permeability, cytotoxicity or particle-mucus interactions. [less ▲]

Detailed reference viewed: 27 (2 ULiège)