D. Betbeder - Academia.edu (original) (raw)

Papers by D. Betbeder

Pharmaceutical Research, 2000

Purpose. We have studied the antinociceptive activity and blood andbrain delivery of nasal morphi... more Purpose. We have studied the antinociceptive activity and blood andbrain delivery of nasal morphine with or without Biovector™nanoparticles in mice.

Pharmaceutical Research, 2011

Purpose Nanomedicines represent an alternative for the treatment of aggressive glioblastoma tumor... more Purpose Nanomedicines represent an alternative for the treatment of aggressive glioblastoma tumors. Behaviour of PLGAnanoparticles (NPs) was here investigated as a function of their protein adsorption characteristics at the different biological interfaces they are expected to face in order to reach brain cancer cells. Methods NPs were studied for size, zeta potential, blood half-life, in vitro endocytic behavior and in vivo accumulation within healthy rat brain and brain tumors. Results While slightly modifying size (80 to 90 nm) and zeta potential (−44 to −32 mV) protein coating of PLGA-NPs by bovine serum albumin (BSA) or transferrin (Tf) greatly prolonged their blood half-life when intravenously injected in rats and mice. In contrast with THP-1 monocytes, differentiated THP-1 macrophages, F98 glioma cells and astrocytes internalized BSA-and Tf-NPs in vitro. Increase of Tf-NP uptake by F98 cells through caveolae-and clathrin-mediated pathways supports specific interaction between Tf and overexpressed Tf-receptor. Finally, in vivo targeting of healthy brain was found higher with Tf-NPs than with BSA-NPs while both NPs entered massively within brain-developed tumors. Conclusion Taken together, those data evidence that Tf-NPs represent an interesting nanomedicine to deliver anticancer drugs to glioma cells through systemic or locoregional strategies at early and late tumor stages. KEY WORDS blood-brain barrier. central nervous system. glioma. PLGA nanocarriers. stealth. targeting J. Chang and A. Paillard contributed equally to this work.

Vaccine, Jan 2, 2008

In order to study the influence of antigen composition, spatial organization of antigen and the r... more In order to study the influence of antigen composition, spatial organization of antigen and the route of administration, four cell culture-derived, inactivated, nonadjuvanted influenza vaccine formulations, i.e. whole inactivated virus (WIV), split, subunit and virosome vaccines were prepared from a single antigen batch. We directly compared the immunogenicity and efficacy of these vaccine formulations after intramuscular (i.m.) or intranasal (i.n.) administration in mice. Prime and boost vaccination were followed by a potentially lethal homologous aerosol challenge. For all vaccines, the i.m. route induced higher serum humoral immune responses as compared to the i.n. route and protected all mice against challenge at a dose of 5 microg. Upon i.n. immunization only WIV and split vaccines induced detectable IgG titers and partial protection against challenge but only very low HI titers were induced in almost all mice. WIV induced mainly IgG2a/c titers via both routes, whereas split va...

Pharmaceutical Research, 2009

Stealth nanoparticles are generally obtained after modifying their surface with hydrophilic polym... more Stealth nanoparticles are generally obtained after modifying their surface with hydrophilic polymers such as PEG. In this study we analysed the effect of a phospholipid (DG) or protein (BSA) inclusion in porous cationic polysaccharide (NP) on their + physico-chemical structure and the effect on complement activation. METHODS NP s were characterised in terms of size, zeta potential () and static light-scattering (SLS). Complement consumption was assessed + ζ in normal human serum (NHS) by measuring the residual haemolytic capacity of the complement system. RESULTS DG-loading did not change their size or whereas progressive BSA loading decreased lightly their. An electrophoretic mobility ζ ζ analysis study showed the presence of 2 differently-charged sublayers at the NP surface which are not affected by DG-loading. + Complement system activation, studied via a CH50 test, was suppressed by DG-or BSA-loading. We also demonstrated that NP s + could be loaded by a polyanionic molecule such as BSA, after their preliminary filling by a hydrophobic molecule such as DG. CONCLUSION These nanoparticles are able to absorb large amounts of phospholipids or proteins without change in their size or zeta potential. Complement studies showed that stealth behaviour is observed when they are loaded and saturated either with anionic phospholipid or proteins.

International Journal of Pharmaceutics

Journal of Controlled Release, 2016

Antiviral Chemistry and Chemotherapy, 1990

International journal of pharmaceutics, Jan 11, 2009

The purpose of this study was to design and characterize two flavonoid-loaded lipid nanocapsules ... more The purpose of this study was to design and characterize two flavonoid-loaded lipid nanocapsules (LNC) by applying the phase inversion process, and to enhance their apparent solubility and/or the stability. The flavonoid-loaded LNC were characterized by particle size, encapsulation efficiency, drug leakage rates, stability and spectroscopic studies. It was observed that quercetin-loaded LNC30 (3%) and LNC60 (2%) carried a particle size of 30.3 and 55.1 nm, respectively and significant higher entrapment efficiency. Encapsulation of quercetin (QC) in LNC enabled us to increase its apparent aqueous solubility by a factor of 100. And in view of calculations and results, it seems most probable that QC is arranged at this LNC interface between the oil phase and the hydrophilic polyethylene glycol moieties of the surfactant. In addition, colloidal suspensions proved to be stable in term of encapsulation for at least 10 weeks and QC was not oxidised. With simple chemical modification of (-)...

International journal of sports medicine, 2006

The disproportionate increase in VO2 ("extra VO2) reported at elevated intensity during incr... more The disproportionate increase in VO2 ("extra VO2) reported at elevated intensity during incremental exercise (IE) might result from the same physiological mechanisms as the VO2 slow component observed during heavy constant work rate exercise (CWRE). Moreover, it has been demonstrated that prior heavy exercise can diminish the VO2 slow component. The aim of this study was to evaluate whether prior heavy exercise also alters the "extra VO2" during IE. Ten trained sprinters performed three tests on a cycle ergometer: Test 1 was an IE; Test 2 consisted of six minutes of a CWRE (90% of VO2max) followed by six minutes at 35 W and by an IE and Test 3 was composed of two CWRE of six minutes separated by six minutes of exercise at 35 W. For each IE, the slope and the intercept of the VO2/work rate relationship were calculated by linear regression using data before the first Ventilatory Threshold (pre-VT1 slope). The difference between VO2max measured and VO2max expected using ...

Pharmaceutical research, 2000

Supramolecular Biovectors (SMBV) consist of cross-linked cationic nanoparticles surrounded by a l... more Supramolecular Biovectors (SMBV) consist of cross-linked cationic nanoparticles surrounded by a lipid membrane. The purpose was to study the structure of the lipid membrane and to characterise its interaction with the nanoparticles in order to differentiate SMBV from other polymer/lipid associations. The interaction of lipids with the nanoparticle surface was studied using zeta potential. Fluorescence Energy Transfer (FET) and Fluorescence Microscopy. SMBV were compared to liposomes and mixtures nanoparticles/liposomes. Finally the structure of SMBV was visualised by Electron Microscopy. Zeta potential measurements showed that lipids on SMBV had a pronounced shielding effect on the surface charge. This was not the case for mixtures of nanoparticles and liposomes. FET experiments confirmed these results indicating that, for SMBV, the lipids are much closer to the nanoparticle surface. SMBV Fluorescence microscopy on model microparticles showed a lipid crown on SMBV that was confirmed...

The Journal of pharmacology and experimental therapeutics, 1999

A cell culture model of the blood-brain barrier (BBB) consisting of a coculture of bovine brain c... more A cell culture model of the blood-brain barrier (BBB) consisting of a coculture of bovine brain capillary endothelial cells and rat astrocytes has been used to examine the ability of 60-nm nanoparticles with different physicochemical characteristics to cross the BBB. Neutral, anionic, and cationic nanoparticles were made from crosslinked malto-dextrins derivatized or not (neutral) with phosphates (anionic), quaternary ammoniums (cationic) ligands. Then, these particles were coated or not with a lipid bilayer made of dipalmitoyl phosphatidyl choline and cholesterol. Lipid coating of ionically charged nanoparticles was able to increase BBB crossing 3- or 4-fold compared with uncoated particles, whereas coating of neutral particles did not significantly alter their permeation characteristics across the endothelial cell monolayer. Lipid-coated nanoparticles were nontoxic toward BBB integrity, and crossed the BBB by transcytosis without any degradation. Furthermore, a 27-fold increase in...

Nucleosides and Nucleotides, 1991

International Journal of Pharmaceutics, 2013

Revue des Maladies Respiratoires, 2007

Revue des Maladies Respiratoires, 2006