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1.
Chemistry ; : e202402634, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39078075

RESUMEN

BODIPYs have a well-established role in biological sciences as chemosensors and versatile biological markers due to their chemical reactivity, which allows for fine-tuning of their photophysical characteristics. In this work, we combined the unique reactivity of arylazo sulfones with the advantages of a "sunflow" reactor to develop a fast, efficient, and versatile method for the photochemical arylation of BODIPYs and other chromophores. This approach resulted in red-shifted emitting fluorophores due to extended electronic delocalization at the 3- and 5-positions of the BODIPY core. This method represents an advantageous approach for BODIPY functionalization compared to existing strategies.

2.
J Control Release ; 372: 417-432, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38908758

RESUMEN

This study introduces the nanobromhexine lipid particle (NBL) platform designed for effective pulmonary drug delivery. Inspired by respiratory virus transport mechanisms, NBL address challenges associated with mucus permeation and inflammation in pulmonary diseases. Composed of low molecular weight polyethylene glycol-coated lipid nanoparticles with bromhexine hydrochloride, NBL exhibit a size of 118 ± 24 nm, a neutral zeta potential, osmolarity of 358 ± 28 mOsmol/kg, and a pH of 6.5. Nebulizing without leakage and showing no toxicity to epithelial cells, NBL display mucoadhesive properties with a 60% mucin-binding efficiency. They effectively traverse the dense mucus layer of Calu-3 cultures in an air-liquid interface, as supported by a 55% decrease in MUC5AC density and a 29% increase in nanoparticles internalization compared to non-exposed cells. In assessing immunomodulatory effects, NBL treatment in SARS-CoV-2-infected lung cells leads to a 40-fold increase in anti-inflammatory MUC1 gene expression, a proportional reduction in pro-inflammatory IL-6 expression, and elevated anti-inflammatory IL-10 expression. These findings suggest a potential mechanism to regulate the excessive IL-6 expression triggered by virus infection. Therefore, the NBL platform demonstrates promising potential for efficient pulmonary drug delivery and immunomodulation, offering a novel approach to addressing mucus permeation and inflammation in pulmonary diseases.


Asunto(s)
Pulmón , Nanopartículas , SARS-CoV-2 , Nanopartículas/administración & dosificación , Humanos , Pulmón/metabolismo , SARS-CoV-2/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Inmunomodulación , Línea Celular , Mucina-1/metabolismo , COVID-19 , Lípidos/química , Lípidos/administración & dosificación , Moco/metabolismo , Polietilenglicoles/química , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Tratamiento Farmacológico de COVID-19 , Mucina 5AC/metabolismo , Liposomas
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