ABSTRACT
The determination of the nanocarrier fate in preclinical models is required before any translation from laboratory to clinical trials. Modern fluorescent imaging techniques have gained considerable advances becoming a powerful technology for non-invasive visualization in living subjects. Among them, Forster (fluorescence) resonance energy transfer (FRET) is a particular fluorescence imaging which involves energy transfer between 2 fluorophores in a distance-dependent manner. Considering this feature, the encapsulation of an acceptor/donor pair in lipid nanoparticles (LNEs: lipid nanoemulsions, LNCs: lipid nanocapsules) allowed the carrier integrity to be tracked. Accordingly, we used this FRET technique to evaluate the behavior of LNEs, conventional LNCs and newly designed stealth LNCs. After the development through a one-step (OS) PEGylation process of these stealth LNCs (OS LNCs), in vitro guest exchange dynamics and release kinetics were evaluated for both LNC formulations. We thereafter assessed in vivo biodistribution of all types of lipid nanoparticles. Results showed enhanced stability of encapsulation in OS LNCs in comparison to conventional LNCs. Additionally, the presence of the long PEG chains on the lipid nanoparticle surface altered the biodistribution pattern. Despite different release kinetic profiles, OS LNCs and LNEs showed extended blood circulation time associated with a good structure stability over several hours after intravenous injection.
Subject(s)
Fluorescence Resonance Energy Transfer/methods , Fluorescent Dyes/administration & dosage , Lipids/chemistry , Nanocapsules/chemistry , Optical Imaging/methods , Animals , Drug Carriers/chemistry , Female , Fluorescent Dyes/pharmacokinetics , Mice, Nude , Polyethylene Glycols/chemistry , Tissue DistributionABSTRACT
The authors, by performing in vitro perfusion on six human placentas, have studied the passage of chloroquine sulphate into the placenta. The drug levels were recorded by high performance liquid chromatography (HPLC). The placental perfusions lasted one hour and drug passage into placental tissue was low (14.21%) which seems to be due to the high degree of fixation of chloroquine on placental tissue.
Subject(s)
Chloroquine/metabolism , Placenta/metabolism , Female , Humans , In Vitro Techniques , Maternal-Fetal Exchange , Pregnancy , Time FactorsABSTRACT
Two cases of multiple coronary aneurysms are reported in patients aged 15 and 25 years. The clinical presentation in both cases was myocardial infarction. The diagnosis was confirmed by the demonstration of rounded calcification at the border of the aneurysms on chest X-Ray, and multiple aneurysmal dilatations on selective coronary angiography. These two cases and the other 16 found in the medical litterature allow analysis of the clinical signs of idiopathic coronary aneurysms, generally these of acute coronary insufficiency. Two-dimensional echocardiography seems to be the most effective means of detecting this type of pathology. The incidence of coronary aneurysms during infantile periarteritis nodosa, and in Kawasaki's syndrome, very similar conditions affecting infants and children, suggest that these two diseases may play a role in the formation of coronary aneurysms in adolescents and young adults, which would therefore be sequellae of an inflammatory arteritis of childhood.
