RESUMO
Nanotechnology is a very promising technological tool to combat health problems associated with the loss of effectiveness of currently used antibiotics. Previously, we developed a formulation consisting of a chitosan and tween 80-decorated alginate nanocarrier that encapsulates rifampicin and the antioxidant ascorbic acid (RIF/ASC), intended for the treatment of respiratory intracellular infections. Here, we investigated the effects of RIF/ASC-loaded NPs on the respiratory mucus and the pulmonary surfactant. In addition, we evaluated their cytotoxicity for lung cells in vitro, and their biodistribution on rat lungs in vivo after their intratracheal administration. Findings herein demonstrated that RIF/ASC-loaded NPs display a favorable lung biocompatibility profile and a uniform distribution throughout lung lobules. RIF/ASC-loaded NPs were mainly uptaken by lung macrophages, their primary target. In summary, findings show that our novel designed RIF/ASC NPs could be a suitable system for antibiotic lung administration with promising perspectives for the treatment of pulmonary intracellular infections.
Assuntos
Alginatos/química , Ácido Ascórbico/química , Pneumopatias/tratamento farmacológico , Pneumopatias/metabolismo , Nanopartículas/química , Rifampina/metabolismo , Rifampina/toxicidade , Células A549 , Alginatos/metabolismo , Alginatos/toxicidade , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/toxicidade , Ácido Ascórbico/metabolismo , Ácido Ascórbico/toxicidade , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/fisiologia , Linhagem Celular , Linhagem Celular Tumoral , Quitosana/metabolismo , Quitosana/toxicidade , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/toxicidade , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/metabolismo , Masculino , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/toxicidade , Polímeros/metabolismo , Polímeros/toxicidade , Ratos , Ratos Wistar , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Rifampina/farmacologia , Suínos , Distribuição TecidualRESUMO
c-Fos, a transcription factor, associates to endoplasmic reticulum and modulates phospholipid biosynthesis. Its surface thermodynamic properties allow it to differentially interact with phospholipid monolayers with a selective dependence on the lipid polar head group and the lateral surface pressure. We explored the c-Fos ability to modulate phospholipid degradation by phospholipases (ppPLA2, Bacillus cereus PLC, and sphingomyelinase) using the monolayer technique. Experiments conducted under constant packing conditions show that c-Fos modulates phospholipase activity in a finely tuned way, depending on the membrane intermolecular packing. Surface lateral pressures above 12-16 mN/m induce c-Fos to activate phospholipase A2 and sphingomyelinase, and abolish phospholipase C activity. The effects of c-Fos on other steps of the catalytic process, lag-time and extent, are synergic with those on activity. We show for the first time that c-Fos participates in modulating phospholipid degradation and that it can affect the formation of lipid second messenger products by PLA2, PLC, and sphingomyelinase.