RESUMO
Mesoporous silica nanoparticles (MSNs) exhibit unique drug delivery properties and are thus considered as promising candidates for next generation nano-medicines. In particular, inhalation into the lungs represents a direct, non-invasive delivery route for treating lung disease. To assess MSN biocompatibility in the lung, we investigated the bioresponse of avidin-coated MSNs (MSN-AVI), as well as aminated (uncoated) MSNs, after direct application into the lungs of mice. We quantified MSN distribution, clearance rate, cell-specific uptake, and inflammatory responses to MSNs within one week after instillation. We show that amine-functionalized (MSN-NH2) particles are not taken up by lung epithelial cells, but induced a prolonged inflammatory response in the lung and macrophage cell death. In contrast, MSN-AVI co-localized with alveolar epithelial type 1 and type 2 cells in the lung in the absence of sustained inflammatory responses or cell death, and showed preferential epithelial cell uptake in in vitro co-cultures. Further, MSN-AVI particles demonstrated uniform particle distribution in mouse lungs and slow clearance rates. Thus, we provide evidence that avidin functionalized MSNs (MSN-AVI) have the potential to serve as versatile biocompatible drug carriers for lung-specific drug delivery.
Assuntos
Portadores de Fármacos/química , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Nanopartículas , Animais , Avidina , Linhagem Celular , Técnicas de Cocultura , Citocinas/metabolismo , Sistemas de Liberação de Medicamentos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Mediadores da Inflamação/metabolismo , Pulmão/citologia , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Nanomedicina , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanopartículas/toxicidade , Dióxido de SilícioRESUMO
The results from this double-blind, multi-investigator study showed that a combination of 50 mg triamterene plus 25 mg hydrochlorothiazide and a combination of 25 mg spironolactone plus 25 mg hydrochlorothiazide were equally efficacious in lowering blood pressure in hypertensive outpatients, and that they produced the same type and incidence of adverse effects. Likewise, the two drug combinations produced similar effects on blood chemistry and hematology. There were no significant differences between the two combination drugs in efficacy laboratory studies, or adverse effects.
