References of "Piel, Géraldine"
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See detailWhole blood microsampling for the quantitation of estetrol without derivatization by liquid chromatography-tandem mass spectrometry
Nys, Gwenaël ULg; Gallez, Anne ULg; Kok, Miranda ULg et al

in Journal of Pharmaceutical & Biomedical Analysis (2017), 140

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See detailEnhancement of the internalization of lipid nanocapsules in human glioblastoma cells: Effect of surface concentration of NFL peptide
Karim, Reatul ULg; Lepeltier, Elise; Palazzo, Claudio ULg et al

Poster (2017)

Le glioblastome multiforme (GBM) est un des cancers les plus fatal, avec une médiane de survie de 14 mois après traitement. Il est donc nécessaire de développer de nouvelles thérapies plus efficaces. La ... [more ▼]

Le glioblastome multiforme (GBM) est un des cancers les plus fatal, avec une médiane de survie de 14 mois après traitement. Il est donc nécessaire de développer de nouvelles thérapies plus efficaces. La fonctionnalisation en surface de nanocapsules lipidiques (LNC) avec le peptide NFL-TBS.40-63 (NFL) a déjà montré une amélioration de leur internalisation dans des cellules de glioblastome murin. Le but de cette étude a été d’évaluer l’impact de la concentration en NFL présente en surface des LNC sur l’internalisation de ces dernières dans des cellules humaines de GBM U87MG. De plus, le mécanisme d’internalisation LNC-NFL a été étudié. Une sonde fluorescente (DiA) a été encapsulé dans : des LNC (F1), des LNC avec 0.86 % et 2.58 % (w/w) de NFL adsorbé à la surface (F2 et F3 respectivement). Des analyses par cytométrie en flux (FACS) ont révélé une internalisation cellulaire de F3 plus importante de 46.4 et 6.8 fois après 30 min, de 21.6 et 6.1 fois après 1 heure, de 31.5 et 1.6 fois après 6 heures et de 7.3 et 1.1 fois après 24 heures, comparés à F1 et F2 respectivement. L’internalisation de F3 dans les cellules U87MG s’est révélée être énergie-dépendant, avec comme mécanisme principal la macropinocytose. Les cinétiques de désorption du peptides (obtenues par dialyse de F3 dans du Tris-Buffer pH 7.4 à 37°C suivi par une HPLC analytique) ont montré que 66 % de NFL restaient à la surface des LNC après 6h de dialyse, montrant une désorption lente. De plus, les trois formulations ont montré une faible activation du complément. Du fait d’une internalisation significativement plus prononcée et rapide, F3 semble être prometteur pour améliorer l’efficacité des thérapies antiGBM. De plus, la lente désorption du NFL de la surface des LNC et la faible consommation du complément font de F3 une thérapie ciblé prometteuse contre le GBM. [less ▲]

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See detailDevelopment and evaluation of injectable nanosized drug delivery systems for apigenin
Karim, Reatul ULg; Palazzo, Claudio ULg; Laloy, Julie et al

in International Journal of Pharmaceutics (2017)

The purpose of this study was to develop different injectable nanosized drug delivery systems (NDDSs) i.e. liposome, lipid nanocapsule (LNC) and polymeric nanocapsule (PNC) encapsulating apigenin (AG) and ... [more ▼]

The purpose of this study was to develop different injectable nanosized drug delivery systems (NDDSs) i.e. liposome, lipid nanocapsule (LNC) and polymeric nanocapsule (PNC) encapsulating apigenin (AG) and compare their characteristics to identify the nanovector(s) that can deliver the largest quantity of AG while being biocompatible. Two liposomes with different surface characteristics (cationic and anionic), a LNC and a PNC were prepared. A novel tocopherol modified poly(ethylene glycol)-b-polyphosphate block-copolymer was used for the first time for the PNC preparation. The NDDSs were compared by their physicochemical characteristics, AG release, storage stability, stability in serum, complement consumption and toxicity against a human macrovascular endothelial cell line (EAhy926). The diameter and surface charge of the NDDSs were comparable with previously reported injectable nanocarriers. The NDDSs showed good encapsulation efficiency and drug loading. Moreover, the NDDSs were stable during storage and in fetal bovine serum for extended periods, showed low complement consumption and were non-toxic to EAhy926 cells up to high concentrations. Therefore, they can be considered as potential injectable nanocarriers of AG. Due to less pronounced burst effect and extended release characteristics, the nanocapsules could be favorable approaches for achieving prolonged pharmacological activity of AG using injectable NDDS. [less ▲]

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See detailStudy of virus-like particles of human papillomavirus in capillary electrophoresis
Bettonville, Virginie ULg; Nicol, Jérôme; Furst, Tania et al

Poster (2017)

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See detailPEGylated and Functionalized Aliphatic Polycarbonate Polyplex Nanoparticles for Intravenous Administration of HDAC5 siRNA in Cancer Therapy
Frère, Antoine ULg; Baroni, Alexandra; Hendrick, Elodie ULg et al

in ACS Applied Materials and Interfaces (2017), 25(9(3)), 2181-2195

Guanidine and morpholine functionalized aliphatic polycarbonate polymers are able to efficiently deliver histone deacetylase 5 (HDAC5) siRNA into the cytoplasm of cancer cells in vitro leading to a ... [more ▼]

Guanidine and morpholine functionalized aliphatic polycarbonate polymers are able to efficiently deliver histone deacetylase 5 (HDAC5) siRNA into the cytoplasm of cancer cells in vitro leading to a decrease of cell proliferation were previously developed. To allow these biodegradable and biocompatible polyplex nanoparticles to overcome the extracellular barriers and be effective in vivo after an intravenous injection, polyethylene glycol chains (PEG750 or PEG2000) were grafted on the polymer structure. These nanoparticles, showed an average size of about 150 nm and a slightly positive zeta potential with complete siRNA complexation. Behavior of PEGylated and non-PEGylated polyplexes were investigated in the presence of serum, in terms of siRNA complexation (Fluorescence Correlation Spectroscopy), size (Dynamic Light Scattering and Single-Particle Tracking), interaction with proteins (Isothermal Titration Calorimetry) and cellular uptake. Surprisingly, both PEGylated and non-PEGylated formulations presented relatively good behavior in the presence of fetal bovine serum (FBS). Hemocompatibility tests showed no effect of these polyplexes on hemolysis and coagulation. In vivo biodistribution in mice was performed and showed a better siRNA accumulation at the tumor site for PEGylated polyplexes. However, cellular uptake in protein-rich conditions showed that PEGylated polyplex lost their ability to interact with biological membranes and enter into cells, showing the importance to perform in vitro investigations in physiological conditions closed to in vivo situation. In vitro, the efficiency of PEGylated nanoparticles decreases compared to non-PEGylated particles, leading to the loss of the antiproliferative effect on cancer cells. [less ▲]

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See detailNEW INJECTABLE LIPOSOME AND DRUG-IN-CYCLODEXTRIN-IN LIPOSOME SYSTEMS ENCAPSULATING ESTETROL FOR THE TREATMENT OF ISCHEMIA DISEASES IN PREMATURE BABIES
Palazzo, Claudio ULg; Laloy, Julie; Delvigne, Anne-Sophie et al

Poster (2016, December)

Purpose: In 2010, almost 15 million of babies in the world are prematurely borned, 11.1 % of the total amount of alive children. Despite the better neonatology techniques, the number of preterm babies ... [more ▼]

Purpose: In 2010, almost 15 million of babies in the world are prematurely borned, 11.1 % of the total amount of alive children. Despite the better neonatology techniques, the number of preterm babies with motor, vision, hearing or mental deficiencies is still constant along the last twenty years. Moreover, no efficacy treatment is available to the present day. The estetrol (E4) 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). Methods: Cyclodextrins (CD) were used to increase E4 aqueous solubility. Liposome and DCL (E4-CD complex) formulations were prepared by thin-film hydration technique. The formulations were physicochemical characterized. LDH and MTS tests on endothelial, neuronal and BBB model cells were performed in vitro on the liposome formulation. Hemocompatibility of the formulations was evaluated on red blood cells, platelet aggregation and coagulation. BBB passage tests were performed using human BBB cell line (hCMEC/D3). Results: E4-CD complexes proportionally increased the solubility of the hormone. Liposomes and DCL encapsulating E4 were prepared. 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%. Moreover, the formulations are capable to release 80 % (liposome) and 90 % (DCL) of encapsulated E4 after 3 h at 37°C. 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. Conclusions: New non-toxic, hemocompatible liposome and DCL formulations encapsulating E4 were prepared. The formulations are promising drug delivery system to target estrogens to the brain, due to their physiochemical characteristics. [less ▲]

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See detailDevelopment and comparison of liposomes and nanocapsules as injectable nanocarriers for poorly aqueous soluble drugs
Karim, Reatul ULg; Palazzo, Claudio ULg; Laloy, Julie et al

Poster (2016, December)

About 90% of drugs in development phase have poor aqueous solubility. Liposomes and nanocapsules are promising approaches that enable parenteral administration of these drugs with possibilities of site ... [more ▼]

About 90% of drugs in development phase have poor aqueous solubility. Liposomes and nanocapsules are promising approaches that enable parenteral administration of these drugs with possibilities of site specific delivery. The objective of the study was to develop different liposomes and lipid nanocapsules entrapping a hydrophobic model molecule (apigenin (AG)), and to characterize and compare them as potential injectable nanocarriers (NCs) for drugs with low aqueous solubility. [less ▲]

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See detailINNOVATIVE INJECTABLE LIPOSOME AND DRUG-IN-CYCLODEXTRIN-IN LIPOSOME SYSTEMS ENCAPSULATING ESTETROL FOR THE TREATMENT OF ISCHEMIA DISEASES IN PREMATURE BABIES
Palazzo, Claudio ULg; Laloy, Julie; Delvigne, Anne-Sophie et al

Conference (2016, September 28)

Purpose: In 2010, almost 15 million of babies in the world are prematurely borned, 11.1 % of the total amount of alive children. Despite the better neonatology techniques, the number of preterm babies ... [more ▼]

Purpose: In 2010, almost 15 million of babies in the world are prematurely borned, 11.1 % of the total amount of alive children. Despite the better neonatology techniques, the number of preterm babies with motor, vision, hearing or mental deficiencies is still constant along the last twenty years. Moreover, no efficacy treatment is available to the present day. The estetrol (E4) 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). Methods: Hydroxypropyl-β-cyclodextrins (degrees of substitution 0.87 and 0.63) (HPβCD 0.87 and HPβCD 0.63) were used to increase E4 aqueous solubility. Liposome and DCL (E4-HPβCD 0.63 complex) formulations were prepared by thin-film hydration technique. The formulations were physicochemical characterized and stability in foetal bovine serum (FBS) was evaluated. LDH and MTS tests on endothelial, neuronal and BBB model cells were performed in vitro on the liposome formulation. Hemocompatibility of the formulations was evaluated on red blood cells, platelet aggregation and coagulation. BBB passage tests were performed using human BBB cell line (hCMEC/D3). Results: E4-HPβCD complexes proportionally increased the solubility of the hormone. Due to the lower solubility obtained with HPβCD ds 0.87, only HPβCD ds 0.63 was retained for future tests. Liposomes and DCL encapsulating E4 were prepared. 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%. Moreover, the formulations are capable to release 80 % (liposome) and 90 % (DCL) of encapsulated E4 after 3 h at 37°C. The formulations, incubated in FBS at 37°C under gentle stirring, keep the same size and do not form protein corona up to 6 h. 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. Preliminary BBB passage tests highlighted the capability of the formulations to pass the BBB and reach the brain. Conclusions: New non-toxic, hemocompatible liposome and DCL formulations encapsulating E4 were prepared. The formulations are promising drug delivery system to target estrogens to the brain, due to their physiochemical characteristics. Aknowledgment : The authors thank Estetra SPRL for providing Estetrol. [less ▲]

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See detailDEVELOPMENT OF NOVEL CATIONIC AND LIGAND-GRAFTED ANIONIC LIPOSOMES FOR BRAIN-TARGETED DRUG DELIVERY
Karim, Reatul ULg; Palazzo, Claudio ULg; Laloy, Julie et al

Poster (2016, September 27)

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See detailMUCOADHESIVE SPONGES WITH PEGYLATED LIPOPLEXES: TOWARDS A SUSTAINED VAGINAL DELIVERY OF siRNA
Furst, Tania ULg; Dakwar, Georges; zagato, Elisa et al

Poster (2016, September 26)

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See detailPEGylation of lipoplexes: The right balance between cytotoxicity and siRNA effectiveness
Lechanteur, Anna ULg; Furst, Tania ULg; Evrard, Brigitte ULg et al

in European Journal of Pharmaceutical Sciences (2016), 93

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See detailPolymeric Nanoparticles as siRNA Drug Delivery System for Cancer Therapy: The Long Road to Therapeutic Efficiency
Frère, Antoine ULg; Evrard, Brigitte ULg; Mottet, Denis ULg et al

in Holban, Alina Maria; Grumezescu, Alexandru (Eds.) Nanoarchitectonics for Smart Delivery and Drug Targeting (2016)

Polyplexes are nanoparticles composed of small-interfering RNA (siRNA) and natural or synthetic polymers. To meet the challenge of gene therapy and deliver siRNA into the cytoplasm of target cells ... [more ▼]

Polyplexes are nanoparticles composed of small-interfering RNA (siRNA) and natural or synthetic polymers. To meet the challenge of gene therapy and deliver siRNA into the cytoplasm of target cells, several barriers must be overcome. In this chapter, the main steps, from the formulation of polyplexes to the efficient release of the siRNA into the cytoplasm of cancer cells, are described, taking into account the different strategies used to overcome the obstacles linked to the formulation of this type of nanovector. To allow a parenteral administration of the nanocolloids, the polyplex production methods should result in identical, stable, and reproducible nanostructures. Charge interactions occur between the anionic siRNA and the cationic/amphiphilic polymer. Once in the blood circulation, polyplexes must keep their physical stability. The positively charged surface can cause aggregation of the nanoparticles with plasma proteins, as well as complement activation and recognition by the mononuclear phagocytic system, with a consequent reduction of their pharmacological activity. Polyethylene glycol (PEG) can be added on the surface of the nanovectors to confer “the stealth” properties and increase plasma half-life. Then, particles have to preferentially accumulate in the tumor tissue following an active or passive targeting. Endocytosis process enables the polyplex cellular uptake, but some strategies like “the proton sponge effect” have to be used to allow the escape of the nanovectors from the cellular endosomes. Once released into the cytoplasm, polymer and siRNA must dissociate for an effective degradation of the targeted mRNA, leading finally to a decrease of the corresponding protein. [less ▲]

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See detailCapillary electrophoresis method to determine siRNA complexation with cationic liposomes
Furst, Tania ULg; Bettonville, Virginie ULg; Farcas, Elena ULg et al

in Electrophoresis (2016)

Small interfering RNA (siRNA) inducing gene silencing has great potential to treat many human diseases. To ensure effective siRNA delivery, it must be complexed with an appropriate vector, generally ... [more ▼]

Small interfering RNA (siRNA) inducing gene silencing has great potential to treat many human diseases. To ensure effective siRNA delivery, it must be complexed with an appropriate vector, generally nanoparticles. The nanoparticulate complex requires an optimal physiochemical characterization and the complexation efficiency has to be precisely determined. The methods usually used to measure complexation are gel electrophoresis and RiboGreen® fluorescence-based assay. However, those approaches are not automated and present some drawbacks such as the low throughput and the use of carcinogenic reagents. The aim of this work is to develop a new simple and fast method to accurately quantify the complexation efficiency. In this research, capillary electrophoresis (CE) was used to determine the siRNA complexation with cationic liposomes. The short-end injection mode applied enabled siRNA detection in less than 5 min. Moreover, the CE technique offers many advantages compared to the other classical methods. It is automated, does not require sample preparation and expensive reagents. Moreover, no mutagenic risk is associated to CE approach since no carcinogenic product is used. Finally, this methodology can also be extended to the characterization of other types of nanoparticles encapsulating siRNA, such as cationic polymeric nanoparticles. [less ▲]

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See detailFreeze-dried mucoadhesive polymeric system containing pegylated lipoplexes: Towards a vaginal sustained released system for siRNA
Furst, Tania ULg; Dakwar, George R.; Zagato, Elisa et al

in Journal of Controlled Release (2016)

Topical vaginal sustained delivery of siRNA presents a significant challenge due to the short residence time of formulations. Therefore, a drug delivery system capable to adhere to the vaginal mucosa is ... [more ▼]

Topical vaginal sustained delivery of siRNA presents a significant challenge due to the short residence time of formulations. Therefore, a drug delivery system capable to adhere to the vaginal mucosa is desirable, as it could allow a prolonged delivery and increase the effectiveness of the therapy. The aim of this project is to develop a polymeric solid mucoadhesive system, loaded with lipoplexes, able to be progressively rehydrated by the vaginal fluids to form a hydrogel and to deliver siRNA to vaginal tissues. To minimize adhesive interactions with vaginal mucus components, lipoplexes were coated with different derivatives of polyethylene glycol: DPSE-PEG2000, DPSE-PEG750 and ceramide-PEG2000. Based on stability and diffusion properties in simulated vaginal fluids, lipoplexes containing DSPE-PEG2000 were selected and incorporated in hydroxyethyl cellulose (HEC) hydrogels. Solid systems, called sponges, were then obtained by freeze-drying. Sponges meet acceptable mechanical characteristics and their hardness, eformability and mucoadhesive properties are not influenced by the presence of lipoplexes. Finally, mobility and stability of lipoplexes inside sponges rehydrated with vaginal mucus, mimicking in situ conditions, were evaluated by advanced fluorescence microscopy. The release rate was found to be influenced by the HEC concentration and consequently by the viscosity after rehydration. This study demonstrates the feasibility of entrapping pegylated lipoplexes into a solid matrix system for a prolonged delivery of siRNA into the vagina. [less ▲]

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