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1.
Environ Int ; 167: 107397, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35933843

RESUMO

Polychlorinated biphenyls (PCBs) were used in a number of industrial products from 1950 to 80s, including building materials. As a result, some buildings exhibit high levels of PCBs in the indoor environment. The aim of this study was to test silicone wristbands as a method for estimating personal exposure to PCBs in buildings both in controlled experiments and field settings. In the controlled study, the sampling kinetics of silicone wristbands were investigated in a 31-day uptake study. The field study focused on the application of wristbands as a personal exposure measure. It included 71 persons in a contaminated housing estate and 23 persons in a reference group. The linear uptake of PCBs ranged from 2 to 24 days for PCB-8, 18, 28, 31, 40, 44, 49, 52, 66, 99, and 101 under controlled conditions. A generic sampling rate (Rk) of 2.3 m3 d-1 corresponding to a mass transfer coefficient of 17 m h-1 was found in the controlled kinetic study. Partitioning coefficients were also determined for the nine congeners. In the field study, an apparent generic field sampling rate (Rf) of 2.6 m3 d-1 was found; when adjusted to reported hours exposed, it increased to 3.5 m3 d-1. The wristbands were shown to be a good tool for predicting airborne exposure, as there was a highly significant difference between the exposed and reference group as well as a clear trend when used for ranking of exposure. In correlation analyses, highly significant correlations were observed between air and wristband levels, though adjusting by self-reported exposure time only increased the correlation marginally in the field study. The obtained kinetic data can be used for estimating the magnitude of external exposure. The advantages provided by the wristbands in the form of easy use and handling are significant, though the limitations should also be acknowledged.


Assuntos
Poluição do Ar em Ambientes Fechados , Bifenilos Policlorados , Poluição do Ar em Ambientes Fechados/análise , Materiais de Construção , Monitoramento Ambiental/métodos , Humanos , Bifenilos Policlorados/análise , Silicones
2.
Mol Pharm ; 16(11): 4725-4737, 2019 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-31539263

RESUMO

Designing effective and safe tuberculosis (TB) subunit vaccines for inhalation requires identification of appropriate antigens and adjuvants and definition of the specific areas to target in the lungs. Magnetic resonance imaging (MRI) enables high spatial resolution, but real-time anatomical and functional MRI of lungs is challenging. Here, we describe the design of a novel gadoteridol-loaded cationic adjuvant formulation 01 (CAF01) for MRI-guided vaccine delivery of the clinically tested TB subunit vaccine candidate H56/CAF01. Gadoteridol-loaded CAF01 liposomes were engineered by using a quality-by-design approach to (i) increase the mechanistic understanding of formulation factors governing the loading of gadoteridol and (ii) maximize the loading of gadoteridol in CAF01, which was confirmed by cryotransmission electron microscopy. The encapsulation efficiency and loading of gadoteridol were highly dependent on the buffer pH due to strong attractive electrostatic interactions between gadoteridol and the cationic lipid component. Optimal gadoteridol loading of CAF01 liposomes showed good in vivo stability and safety upon intrapulmonary administration into mice while generating 1.5-fold MRI signal enhancement associated with approximately 30% T1 relaxation change. This formulation principle and imaging approach can potentially be used for other mucosal nanoparticle-based formulations, species, and lung pathologies, which can readily be translated for clinical use.


Assuntos
Cátions/química , Compostos Heterocíclicos/administração & dosagem , Compostos Heterocíclicos/química , Lipossomos/química , Pulmão/efeitos dos fármacos , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/química , Adjuvantes Imunológicos/química , Adjuvantes Farmacêuticos , Animais , Química Farmacêutica/métodos , Feminino , Gadolínio/administração & dosagem , Gadolínio/química , Lipídeos/química , Imageamento por Ressonância Magnética/métodos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Tuberculose/tratamento farmacológico , Vacinas contra a Tuberculose/química , Vacinas de Subunidades Antigênicas/química
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