Biomedical subjects

M Marlard

Publications and source records attributed to M Marlard.

5 recordsLinked to original sources

PubMed1995

Stealth Me.PEG-PLA nanoparticles avoid uptake by the mononuclear phagocytes system.

Nanoparticles were prepared from methoxy poly(ethylene glycol)poly(d,l-lactic acid) block copolymers (Me.PEG-PLA) or blends of Me.PEG-PLA and PLA by the precipitation-solvent diffusion method. These nanoparticles, labeled by introducing [14C]PLA in the formulation, were shown to be more slowly captured by cultured THP-1 monocytes than F68-coated PLA nanoparticles, in a PEG chain-length-dependent manner. In vivo, the half-life in plasma of the Me.PEG-PLA nanoparticles that were intravenously administered to rats is increased by a factor 180 compared with the F68-coated PLA nanoparticles. This mononuclear phagocytes system avoidance was explained according to a conformation model in which the PEG density at the surface of the particles is a key parameter.

Animals↗

PubMed1992

Body distribution of fully biodegradable [14C]-poly(lactic acid) nanoparticles coated with albumin after parenteral administration to rats.

Fully biodegradable polylactic acid (PLA) nanoparticles (90-250 nm) coated with human serum albumin (HSA) were prepared by high-pressure emulsification and solvent evaporation, using the protein as surfactant. A new analytical tool was developed, based on Mie's law and size exclusion chromatography, to establish that, after evaporation of the solvent, the protein saturates the surface of the nanoparticles, masking the PLA core. According to this technique, no HSA is encapsulated in the polymer matrix. A radiolabelled [14C]-PLA50 was synthesized to follow the fate of this new drug carrier after i.v. administration to rats. The time necessary to clear the albumin-coated nanoparticles from the plasma was significantly longer than for the uncoated ones but not extended enough to target cells other than mononuclear phagocytes. As deduced from whole-body autoradiography and quantitative distribution experiments, the 14C-labelled polymer is rapidly captured by liver, bone marrow, lymph nodes, spleen and peritoneal macrophages. Nanoparticle degradation was addressed following 14C excretion. The elimination of the 14C was quick on the first day (30% of the administered dose) but then slowed down. In fact, if the metabolism of the PLA proceeds to lactic acid which is rapidly converted into CO2 via the Krebs cycle (80% of the total excretion was fulfilled by the lungs), anabolism from the lactic acid may also have taken place leading to long-lasting radioactive remnants, by incorporation of 14C into endogenous compounds.

Animals↗

PubMed1985

Autoradiography of tissue distribution of the IIA constituent of the pristinamycins.

The tissue distribution of a radioactive analogue of the IIA constituent of the pristinamycins was studied in female mice by autoradiography. Examination of slides and photographs discloses the presence of the antibiotic on the skin and in the bone marrow only a short time after injection. Elimination of the antibiotic is quick and is mainly through the digestive tract.

Animals↗

PubMed1985

Disposition of 14C-oltipraz in animals. Pharmacokinetics in mice, rats and monkeys. Comparison of the biotransformation in the infected mouse and in the schistosomes.

14C-labelled 4-methyl-5(2-pyrazinyl)-1,2-dithiole-3-thione (14C-oltipraz, 35 972 R.P.) was orally administered to rhesus monkeys (20 mg/kg), rats (50 mg/kg) and female mice infected with Schistosoma mansoni (100 and 250 mg/kg). The absorption of oltipraz varied with the animal species and the dose administered. In each species, the pharmacokinetics of oltipraz in the plasma and red blood cells were generally similar. 40 to 57% of the radioactive dose was excreted in urine, depending on the animal species and dose levels. In the mouse, there was negligible elimination of radioactivity as 14CO2. Whole-body autoradiographic studies in mice showed that, during the first 24 h, radioactivity was present mainly in the gastro-intestinal tract, bile, urine, liver and kidneys. In the male and female worms, the nature and amounts of radioactive products present differed.

Animals↗

PubMed1980

Experimental and clinical activity of a new anthracycline derivative: detorubicin (14-diethoxyacetoxydaunorubicin).

This report concerns the experimental activity and the preliminary clinical results obtained with detorubicin, an anthracycline. Experimentally, in comparison with doxorubicin, detorubicin is less toxic, less immunodepressive, and less mutagenic, its experimental antitumor activity is equal or superior, and differences are found in pharmacokinetics. Its most interesting activities in clinical cancer therapy are found in non-Hodgkin lymphomas, in carcinomas, and in soft-tissue sarcomas.

Animals↗