ABSTRACT
Oral anticoagulant therapy could be advanced using lipid-based nanoparticulate systems. This study examined lipid nanocapsules for their oral absorption potential as the first step in developing oral fondaparinux (Fp) novel carriers. Using phase inversion method and cationic surfactants such as hexadecyltrimethyl ammonium bromide (CTAB) or stearylamine (SA), cationic lipid nanocapsules (cLNCs), loaded with Fp on their surface, were prepared and characterized (zeta potential, size and Fp association efficiency and content). In vivo studies were conducted after single oral increasing doses of Fp-loaded cLNCs (0.5 to 5 mg/kg of Fp) in rats and the concentration of Fp in the plasma was measured by anti-factor Xa activity assay. The monodisperse, (~50 nm), positively charged Fp-cLNCs with high drug loadings demonstrated linear pharmacokinetic profiles of the drug with an increased oral absolute bioavailability (up to ~21%) compatible with therapeutic anticoagulant effect (>0.2 µg/mL).
Subject(s)
Anticoagulants/pharmacokinetics , Lipids/pharmacokinetics , Nanocapsules/chemistry , Polysaccharides/pharmacokinetics , Administration, Oral , Amines/chemistry , Analysis of Variance , Animals , Anticoagulants/administration & dosage , Anticoagulants/chemistry , Area Under Curve , Biological Availability , Cetrimonium , Cetrimonium Compounds/chemistry , Fondaparinux , Lipids/administration & dosage , Lipids/chemistry , Male , Particle Size , Polysaccharides/administration & dosage , Polysaccharides/chemistry , Rats , Rats, WistarABSTRACT
Hematology analysers provide now quick, accurate, and reproducible cell blood counts. However, depending on detection methods, spurious counts may occur. If undetected, such spurious counts may lead to inappropriate medical care and to unneeded explorations. Focusing first on platelet counts, situations leading to spurious decrease include several preanalytical considerations, the major one corresponding to EDTA-induced platelet aggregation and to platelet satellitism around polymorphs. In other instances, related to the presence of small particles mimicking platelets, including fragmented red blood cells, lipids, cryoglobulins, fibrin strands, or cytoplasmic fragments of leukocytes, spurious elevation of platelet count may occur. According to the analyser and to the methods used for the determination of the cell blood count, flags or messages related to these spurious changes differ. For each spurious change, the authors describe the mechanism leading to the anomaly, the way the analysers generate flags, and what should be done to provide accurate results.
