Publications (12)31.16 Total impact
-
Article: New functional degradable and bio-compatible nanoparticles based on poly(malic acid) derivatives for site-specific anti-cancer drug delivery.
[show abstract] [hide abstract]
ABSTRACT: Design of an efficient site-specific drug delivery system based on degradable functional polymers still remains challenging. In this work, we synthesized and characterized three degradable functional polyesters belonging to the poly(malic acid) family: the poly(benzyl malate) (PMLABe), the poly(ethylene glycol)-b-poly(benzyl malate) (PEG(42)-b-PMLABe), the biotin-poly(ethylene glycol)-b-poly(benzyl malate) (Biot-PEG(62)-PMLABe). Starting from these building blocks, we were able to prepare the corresponding well-defined degradable functional nanoparticles whose toxicity was evaluated in vitro on normal and cancer cell lines. Results have evidenced that the prepared nanoparticles did not show any significant cytotoxicity even at high concentrations. A model anti-cancer drug (doxorubicin, Dox) or a fluorescent probe (1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine, DiD oil) has been encapsulated into PMLABe, PEG(42)-PMLABe or Biot-PEG(62)-PMLABe based nanoparticles in order to evaluate, respectively, the in vitro cytotoxicity of Dox-loaded nanoparticles on normal and cancer cell lines and the ligand (biotin) effect on cellular uptake in vitro using mmt 060562 cell line. Dox-loaded PMLABe, PEG(42)-PMLABe or Biot-PEG(62)-PMLABe nanoparticles showed an in vitro cytotoxicity similar to that of free Dox. Moreover, the DiD oil loaded Biot-PEG(62)-PMLABe based nanoparticles showed a better in vitro cellular uptake than ligand-free DiD oil loaded nanoparticles. Both results evidence the great potential of such degradable functional poly(malic acid) derivatives for the design of highly efficient site-specific anti-cancer nanovectors.International journal of pharmaceutics 04/2011; 423(1):84-92. · 2.96 Impact Factor -
Article: Preparation and Characterization of Stealth Archaeosomes Based on a Synthetic PEGylated Archaeal Tetraether Lipid.
[show abstract] [hide abstract]
ABSTRACT: The present studies were focused on the formation and characterization of sterically stabilized archaeosomes made from a synthetic PEGylated archaeal lipid. In a first step, a synthetic archaeal tetraether bipolar lipid was functionalized with a poly(ethylene glycol), PEG, and (PEG(45)-Tetraether) with the aim of coating the archaeosome surface with a sterically stabilizing hydrophilic polymer. In a second step, Egg-PC/PEG(45)-Tetraether (90/10 wt%) archaeosomes were prepared, and their physicochemical characteristics were determined by dynamic light scattering (size, polydispersity), cryo-TEM (morphology), and by high-performance thin layer chromatography (lipid composition), in comparison with standard Egg-PC/PEG(45)-DSPE formulations. Further, a fluorescent dye, the carboxyfluorescein, was encapsulated into the prepared archaeosomes in order to evaluate the potential of such nanostructures as drug carriers. Release studies have shown that the stability of Egg-PC/PEG(45)-Tetraether-based archaeosomes is significantly higher at 37°C than the one of Egg-PC/PEG(45)-DSPE-based liposomes, as evidenced by the slower release of the dye encapsulated into PEGylated archaeosomes. This enhanced stability could be related to the membrane spanning properties of the archaeal bipolar lipid as already described with natural or synthetic tetraether lipids.Journal of drug delivery. 01/2011; 2011:396068. -
Article: Folate PEGylated archaeal lipids: cell targeting and drug delivery.
Journal of Controlled Release 11/2010; 148(1):e115-6. · 5.73 Impact Factor -
Article: Highly efficient gene transfer into hepatocyte-like HepaRG cells: new means for drug metabolism and toxicity studies.
[show abstract] [hide abstract]
ABSTRACT: HepaRG progenitor cells are capable of differentiating into hepatocyte-like cells that express a large set of liver-specific functions. These cells, however, only express small amounts of an important cytochrome P450, the CYP2E1, which limits their use for toxicological studies of drugs metabolized by this pathway. Our aim was to establish an efficient transfection protocol to increase CYP2E1 expression in HepaRG cells. Transfection protocols of the green fluorescent protein (GFP) reporter gene were evaluated using electroporation and cationic lipids belonging to the lipophosphonates, lipophosphoramidates and lipids derived from glycine betaine. Following optimization of the charge ratios, plasmid DNA and formulations with neutral co-lipids, the lipophosphoramidate compounds KLN47 and BSV10, allowed expression of the GFP in approximately 50% of adherent progenitor HepaRG cells, while electroporation targeted GFP expression in approximately 85% of both progenitor and differentiated cells in suspension. Transient enforced expression of active CYP2E1 was also achieved in progenitors and/or differentiated HepaRG cells using the electroporation and the lipophosphoramidate compound BSV10. Importantly, in electroporated cells, CYP2E1 expression level was correlated with a significant increase in CYP2E1-specific enzymatic activity, which opens new perspectives for this CYP-dependent drug metabolism and toxicity studies using HepaRG cells.Biotechnology Journal 03/2010; 5(3):314-20. -
Article: New generation of liposomes called archaeosomes based on natural or synthetic archaeal lipids as innovative formulations for drug delivery.
[show abstract] [hide abstract]
ABSTRACT: Archaeosomes made from natural archaeal membrane lipids and/or synthetic lipid analogues have been extensively studied for potential applications in drug and vaccine delivery over the past decade only. Archaeal-type lipids consist of archaeol (diether) and/or caldarchaeol (tetraether) core structures wherein regularly branched and usually fully saturated phytanyl chains (20-40 carbons in lengths), are attached via ether bonds to the sn-2,3 carbons of the glycerol backbone. Archaeosomes constitute a novel generation of liposomes that exhibit high stabilities to low or high temperatures, acidic or alkaline pH, oxidative conditions, high pressure, action of phospholipases, bile salts and serum proteins. These properties associated with a good safety profile are beneficial for nanotechnological applications in drug and gene delivery. Additionally, archaeosome formulations could be used as efficient carriers of antigens and/or adjuvants promoting antigen-specific, humoral and cell-mediated immune responses, in addition to antigen-specific mucosal immune responses in the vaccinated hosts. The immune responses are well sustained over time, and are subject to strong memory responses. Nanodelivery-based vaccinations using archaeosomes could then represent a promising approach for treating and preventing infections, allergies, and neoplastic or cancer diseases. In this review, the few recent US, World and European patents developing archaeosomes for these biotechnological applications in Health are discussed.Recent patents on drug delivery & formulation. 12/2009; 3(3):206-20. -
Article: PEGylated degradable composite nanoparticles based on mixtures of PEG-b-poly(γ-benzyl L-glutamate) and poly(γ-benzyl L-glutamate).
[show abstract] [hide abstract]
ABSTRACT: In the present work, the possibility to obtain PEGylated nanoparticles from two PBLG derivatives, PEG-b-poly(γ-benzyl L-glutamate), PBLG-PEG-60, and poly(γ-benzyl L-glutamate), PBLG-Bnz-50, by nanoprecipitation has been investigated. Particles were prepared not only from one polymer (PBLG-PEG-60 or PBLG-Bnz-50), but also from mixtures of two PBLG derivatives, PBLG-PEG-60 and PBLG-Bnz-50, in different ratios (90/10, 77/23, and 40/60 wt %). Because of the presence of PEG chains, hydrophilic particles were obtained, which was confirmed by ζ potential measurements (ζ from -13 mV and -21 mV) and by isothermal titration microcalorimetry (ITC). This last technique has shown no heat exchange when BSA was added to PEGylated nanoparticles. Further, complement activation has been evaluated by crossed immuno-electrophoresis demonstrating that the introduction of 77 wt % of PEGylated PBLG chains in the particles was enough to ensure a low complement activation activity. This effect was strongly correlated to the ζ potential of the particles, which decreased with an increase of PEG chains content. Interestingly, such properties are of interest for the preparation of degradable stealth nanocarriers. Moreover, it is suggested that the introduction of a reasonable amount (up to 20 wt %) of a second copolymer in the particle composition can be possible without modifying their stealth character. Moreover, the presence of this second copolymer would help to introduce a second functionality to the particles.Bioconjugate Chemistry 08/2009; 20(8):1490-6. · 4.93 Impact Factor -
Article: Folate-equipped pegylated archaeal lipid derivatives: synthesis and transfection properties.
[show abstract] [hide abstract]
ABSTRACT: We have previously shown that synthetic archaeal lipid analogues are useful vectors for drug/gene delivery. We report herein the synthesis and gene transfer properties of a series of novel di- and tetraether-type archaeal derivatives with a poly(ethylene glycol) (PEG) chain and further equipped with a folic acid (FA) group. The synthetic strategy and the purification by dialysis ensured complete removal of free FA. The lipids were mixed with a conventional glycine betaine-based cationic lipid and the resulting formulations were tested in transfection assays after complexation with plasmid DNA. All four novel co-lipids afforded efficient in vitro gene transfection. Moreover, the FA-equipped derivatives permitted ligand/receptor-based targeted transfection; their activity was inhibited when free FA was added to the transfection medium. These novel archaeal derivatives equipped with FA-PEG moieties may thus be of great interest for targeted in vivo transfection.Chemistry 08/2008; 14(27):8330-40. · 5.93 Impact Factor -
Article: Archaeal Lipids: Innovative Materials for Biotechnological Applications
Annalen der Chemie und Pharmacie 07/2008; 2008(28):4725 - 4744. · 3.10 Impact Factor -
Article: Synthesis and ITC characterization of novel nanoparticles constituted by poly(γ‐benzyl L‐glutamate)‐β‐cyclodextrin
[show abstract] [hide abstract]
ABSTRACT: Imparting desired technological characteristics to polymeric nanoparticles requires the development of original polymers. In the present work, the synthesis and characterization of a novel PBLG-derivative, the poly(γ-benzyl L-glutamate)-β-cyclodextrin (PBLG-β-CD-50), have been carried out. Nanoparticles from either PBLG-β-CD-50 polymer or from mixtures with PBLG have been prepared using a modified nanoprecipitation method. Spherically shaped nanoparticles with diameter in the range of 50–70 nm were obtained, as determined by dynamic laser light scattering and transmission electron microscopy. The presence of a surfactant in the suspension medium had almost no influence on these parameters and was not necessary to the shelf-stability of the suspension. Further, isothermal titration microcalorimetry (ITC) experiments have been used to show unambiguously that about 20% of the cyclodextrins remain functional within the particles. Consequently, this system may be of interest when association of large amounts of hydrophobic drugs to nanoparticles is required. Copyright © 2008 John Wiley & Sons, Ltd.Journal of Molecular Recognition 04/2008; 21(3):169 - 178. · 3.31 Impact Factor -
Article: Synthesis and characterization of novel poly(γ‐benzyl‐L‐glutamate) derivatives tailored for the preparation of nanoparticles of pharmaceutical interest
[show abstract] [hide abstract]
ABSTRACT: Four poly(γ-benzyl-L-glutamate) (PBLG) derivatives bearing at one end specific groups were synthesized by ring-opening polymerization of the corresponding γ-benzyl-L-glutamate N-carboxyanhydride using different amine-terminated initiators. These moieties were chosen to introduce, on demand, specific functionalities in nanoparticles of pharmaceutical interest. The PBLG and PBLG derivatives were characterized by 1H NMR, viscosimetry, Fourier transform infrared spectroscopy and differential scanning calorimetry. Nanoparticles smaller than 100 nm in diameter could be easily prepared from these PBLG derivatives by slight modification of a known nanoprecipitation technique. Copyright © 2006 Society of Chemical IndustryPolymer International 02/2007; 56(3):317 - 324. · 1.90 Impact Factor -
Article: Synthesis and ITC characterization of novel nanoparticles constituted by poly(gamma-benzyl L-glutamate)-beta-cyclodextrin.
[show abstract] [hide abstract]
ABSTRACT: Imparting desired technological characteristics to polymeric nanoparticles requires the development of original polymers. In the present work, the synthesis and characterization of a novel PBLG-derivative, the poly(gamma-benzyl L-glutamate)-beta-cyclodextrin (PBLG-beta-CD-50), have been carried out. Nanoparticles from either PBLG-beta-CD-50 polymer or from mixtures with PBLG have been prepared using a modified nanoprecipitation method. Spherically shaped nanoparticles with diameter in the range of 50-70 nm were obtained, as determined by dynamic laser light scattering and transmission electron microscopy. The presence of a surfactant in the suspension medium had almost no influence on these parameters and was not necessary to the shelf-stability of the suspension. Further, isothermal titration microcalorimetry (ITC) experiments have been used to show unambiguously that about 20% of the cyclodextrins remain functional within the particles. Consequently, this system may be of interest when association of large amounts of hydrophobic drugs to nanoparticles is required.Journal of Molecular Recognition 21(3):169-78. · 3.31 Impact Factor -
Article: Folate‐Equipped Pegylated Archaeal Lipid Derivatives: Synthesis and Transfection Properties
Top co-authors
Top Journals
Institutions
-
2011
-
Université de Rennes 1
Rennes, Brittany, France
-
-
2009–2011
-
French National Centre for Scientific Research
Lyon, Rhone-Alpes, France -
Université Paris-Sud 11
- Faculté de Pharmacie
Paris, Ile-de-France, France
-
-
2008–2010
-
Université de Bretagne Sud
Lorient, Brittany, France
-
