21 research outputs found
Fate of Tableted Freeze-Dried siRNA Lipoplexes in Gastrointestinal Environment
The incorporation of siRNA into nanocarriers is mandatory to facilitate its intracellular delivery, as siRNA itself cannot enter cells. However, the incorporation of these nanocarriers into oral, solid dosage forms and their fate in the gastrointestinal environment is yet to be explored. In the present work, the fate of, (i) naked siRNA, (ii) freshly prepared siRNA lipoplexes, and (iii) tableted siRNA lipoplexes, in simulated gastric and intestinal fluids was studied. The siRNA, either released from or protected within the lipoplexes, was quantified by gel electrophoresis and siRNA efficacy was assessed in cell transfection. The freshly prepared lipoplexes kept their siRNA load and transfection efficiency totally preserved during 1 h of incubation in simulated gastric fluid at 37 °C. However, in simulated intestinal fluid, despite no release of siRNA from lipoplexes after 6 h of incubation, gene silencing efficacy was dramatically decreased even after 1 h of exposure. The lipoplexes obtained from tablets efficiently protected siRNA in simulated gastric fluid, thus preserving the gene silencing efficacy, whereas their incubation in simulated intestinal fluid resulted in a marked siRNA release and decreased gene silencing efficacy. These results provided a detailed explanation for understanding the fate of siRNA in gastrointestinal conditions, when simply loaded in lipoplexes or formulated in the form of tablets
Formes galéniques protectrices de "Saccharomyces boulardii"
S. boulardii est une levure probiotique utilisée comme anti-diarrhéique. Cependant, moins de 1% de levures viables est recouvré dans les fèces après administration orale. Le but de l étude a été de protéger la levure de sa dégradation durant le transit gastro-intestinal. Après avoir étudié les conditions de survie de la levure, des comprimés et des microsphères ont été préparés et évalués. In vitro, la viabilité de la levure est stable pendant 6h à pH6,8 mais diminue significativement dès 5min à pH1,1. Dans ces mêmes conditions, les microsphères et les comprimés protègent la levure de la dégradation à pH1,1, et la libèrent viable à pH6,8. En raison de la mortalité engendrée par la compression, seules les microsphères ont été retenues et enrobées par du chitosan. In vivo, la microencapsulation augmente la libération intestinale du probiotique viable d un facteur 5,5. En conclusion, les microsphères pourraient présenter un intérêt majeur pour les applications thérapeutiques de la levure.PARIS-BIUP (751062107) / SudocSudocFranceF
Formulation et évaluation de nanoparticules polymères bioadhésives destinées à promouvoir l'absorption orale du resveratrol
PARIS-BIUP (751062107) / SudocSudocFranceF
Transfert industriel d'un comprimé à libération modifiée obtenu par compression directe
PARIS-BIUP (751062107) / SudocSudocFranceF
Validation d'une nouvelle source d'héparine purifiée
PARIS-BIUP (751062107) / SudocSudocFranceF
Essai de dissolution (application aux formes à libération prolongée de Diclofénac)
PARIS-BIUP (751062107) / SudocSudocFranceF
If the soup tastes bad, it doesn’t mean the potatoes are the culprit
International audienc
Use of Resveratrol Self-Emulsifying Systems in T/C28a2 Cell Line as Beneficial Effectors in Cellular Uptake and Protection Against Oxidative Stress-Mediated Death
International audienceOsteoarthritis (OA) is the most prevalent rheumatic disease in the world. Although its etiology is still unknown, one of the key processes in OA progression and development is oxidative stress. In this context, resveratrol, a well-known anti-oxidant from the stilbene family, could be of particular interest in future OA therapeutic strategies. However, currently, because of its low bioavaiIabiIity, use of resveratrol in human health is very limited. In this study, we tested two resveratrol self-emulsifying systems previously developed in our laboratory in order to determine if they could improve cellular uptake of resveratrol in a human immortalized chondrocytic cell line (T/C28a2) and enhance protection against oxidative stress. Our results showed that resveratrol self-emulsifying systems were able first to increase cellular tolerance towards resveratrol, and thus decrease resveratrol intrinsic cellular toxicity, allowing the use of higher concentrations, second, to increase resveratrol uptake in membrane and intracellular fractions, and finally, to improve protection against oxidative stress-mediated death in human immortalized chondrocytic cell line T/C28a2. These data suggest that new formulations of resveratrol could be considered as potential beneficial effectors in future OA treatments
Head injury profoundly affects gut microbiota homeostasis: Results of a pilot study
International audienceObjectives: Head injury (HI) induces a hypercatabolic state, dysimmunity, and septic complications that increase morbidity and mortality. Although compromised immune function is usually incriminated in infection occurrence, gut dysbiosis could also be involved in this phenomenon and, to our knowledge, has never been considered. To assess if HI could affect microbiota, we explored the impact of HI on intestinal microbiota in a rodent model of fluid percussion.Methods: Nineteen rats were randomly assigned to two groups: Healthy rats fed ad libitum (n ÂĽ 7) and HI rats (n ÂĽ 12), which received standard enteral nutrition for 4 d. Four days after HI, rats were euthanized and cecal contents were sampled. Cecal microbiota was assessed using real-timequantitative polymerase chain reaction.Results: HI significantly decreased the cecal content of strict anaerobic groups, Bacteroides/Prevotella group (HI 8.9 versus healthy controls 9.3 median log10 colony forming units [CFU]/g, P ÂĽ 0.007), Clostridium cluster XIVab (HI 7.9 versus healthy controls 8.9 median log10 CFU/g, P ÂĽ 0.002), Lactobacillus/Leuconostoc group (HI 8.5 versus healthy controls 9.4 median log10 CFU/g, P ÂĽ 0.044), and Bifidobacterium sp. (HI 3.0 versus healthy controls 8.2 median log10 CFU/g, P < 0.001). In contrast, colonization by Escherichia coli was dramatically increased (HI 10.5 versus healthy controls 7.0 median log10 CFU/g, P < 0.001).Conclusions: HI profoundly modified the gut microbiota homeostasis and thus could contribute to infection in head trauma patients. These preliminary results open a new field of research in the management of patients with HI
Evidence for impairment of hepatic energy homeostasis in head-injured rat
International audienceTraumatic brain injury (TBI) is known to induce a metabolic adaptation characterized by a nitrogen transfer from the periphery to the liver. However, the consequences of TBI on liver energy status are poorly documented. We evaluated the consequences of TBI on liver energy homeostasis in rats. In a first set of experiments, rats were randomized into two groups: a TBI group traumatized by fluid percussion, and an ad libitum fed group (AL) of healthy rats. The rats were sacrificed at 2, 3, or 4 days (D2, D3, and D4, respectively to determine the kinetic of hepatic energy changes). Since TBI leads to a profound anorexia, in a second set of experiments TBI rats received enteral nutrition (TBI-EN group) for 4 days to specifically assess the role of anorexia in the hepatic disturbances. TBI led to a decrease in hepatic glycogen (D2: TBI 3.9 +/- 1.9 vs. AL 18.9 +/- 2.6 mg/g, p < 0.05) and ATP (D2: TBI 540 +/- 57 vs. AL 850 +/- 44 nmol/g, p < 0.05) contents. These effects were not linked to anorexia, since they were observed when rats were fed using continuous enteral nutrition. Interestingly, there was no adaptation of the mitochondrial oxidative capacity to compensate for the increase in energy requirements (cytochrome C oxidase activity: AL, 82 +/- 5; TBI, 82 +/- 4; and TBI-EN, 87 +/- 3 micromol/min/g, NS). These findings demonstrate that TBI is responsible for an impairment of liver energy homeostasis. Moreover, these alterations are related neither to anorexia nor to decreased mitochondrial oxidative capacity