RESUMO
BACKGROUND: For many years, researchers have been interested in investigating airflow and aerosol deposition in the nasal cavities. The nasal airways appear to be a complex geometrical system. Thus, in vitro experimental studies are frequently conducted with a more or less biomimetic nasal replica. AIM: This study is devoted to the development of an anatomically realistic nose model with bilateral nasal cavities, i.e. nasal anatomy, airway geometry and aerodynamic properties as close as possible to in vivo behaviour. METHODS: A specific plastination technique of cephalic extremities was developed by the Anatomy Laboratory at the Saint-Etienne University in the last 10 years. The plastinated models obtained were anatomically, geometrically and aerodynamically validated using several techniques (endoscopy, CT scans, acoustic rhinometry and rhinomanometry). RESULTS: Our plastination model exhibited a high level of anatomic quality, including a very good mucosa preservation. Aerodynamical and geometrical investigations highlighted a global behaviour of plastinated models perfectly in accordance with a nasal decongested healthy subject. CONCLUSIONS: The present plastination model provides a realistic cast of nasal airways, and may be a useful tool for nasal flow, drug delivery and aerosol deposition studies.
Assuntos
Modelos Anatômicos , Materiais Biomiméticos , Feminino , Humanos , Masculino , Polímeros , Rinomanometria , VácuoRESUMO
Nanoparticles (NP) physico-chemical features greatly influence NP/cell interactions. NP surface functionalization is often used to improve NP biocompatibility or to enhance cellular uptake. But in biological media, the formation of a protein corona adds a level of complexity. The aim of this study was to investigate in vitro the influence of NP surface functionalization on their cellular uptake and the biological response induced. 50nm fluorescent silica NP were functionalized either with amine or carboxylic groups, in presence or in absence of polyethylene glycol (PEG). NP were incubated with macrophages, cellular uptake and cellular response were assessed in terms of cytotoxicity, pro-inflammatory response and oxidative stress. The NP protein corona was also characterized by protein mass spectroscopy. Results showed that NP uptake was enhanced in absence of PEG, while NP adsorption at the cell membrane was fostered by an initial positively charged NP surface. NP toxicity was not correlated with NP uptake. NP surface functionalization also influenced the formation of the protein corona as the profile of protein binding differed among the NP types.
Assuntos
Macrófagos/metabolismo , Nanopartículas/química , Proteínas/química , Dióxido de Silício , Animais , Macrófagos/citologia , Camundongos , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Proteínas/metabolismo , Células RAW 264.7 , Dióxido de Silício/química , Dióxido de Silício/farmacologiaRESUMO
We previously reported the synthesis of gadolinium-based nanoparticles (NPs) denoted AGuIX (activation and guiding of irradiation by X-ray) NPs and demonstrated their potential as an MRI contrast agent and their efficacy as radiosensitizing particles during X-ray cancer treatment. Here we focus on the elimination kinetics of AGuIX NPs from the subcellular to whole-organ scale using original and complementary methods such as laser-induced breakdown spectroscopy (LIBS), intravital two-photon microscopy, inductively coupled plasma optical emission spectrometry (ICP-OES), transmission electron microscopy (TEM), and electrospray ionization mass spectrometry (ESI-MS). This combination of techniques allows the exact mechanism of AGuIX NPs elimination to be elucidated, including their retention in proximal tubules and their excretion as degraded or native NPs. Finally, we demonstrated that systemic AGuIX NP administration induced moderate and transient effects on renal function. These results provide useful and promising preclinical information concerning the safety of theranostic AGuIX NPs.