期刊
COLLOIDS AND SURFACES B-BIOINTERFACES
卷 105, 期 -, 页码 92-97出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.colsurfb.2012.12.027
关键词
Pulmonary inhalation; Alveolar macrophage; PLGA microspheres; Tuberculosis; Lung distribution; Lung deposition
资金
- Program for Development of Strategic Research Center in Private Universities
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
Although treatment of pulmonary tuberculosis with respirable microspheres (MS) with an incorporated antituberculosis drug is expected to be highly effective, this treatment seems to achieve a much lesser effect than expected in the case of killing Mycobacterium tuberculosis residing in the lungs. To elucidate the reason for this weaker effect, we examined the distribution and accumulation of respirable MS consisting of poly(lactic-co-glycolic) acid (PLGA) in rat lungs. For this, we delivered the PLGA MS containing fluorescent coumarin 6 or an antituberculosis agent, rifampicin (RFP), by insufflation via the trachea and then determined the pulmonary distribution by counting the number of the MS in lung cryosections observed under a microscope. In addition, the uptake of MS by alveolar macrophage (AM phi) was determined by immunostaining for M phi cell marker CD68 and RFP content in the cells. Approximately half of the fluorescent PLGA MS reached the alveoli without entrapment by trachea and primary bronchi and were then ingested by the AM phi cells up to 24 h after insufflation. RFP in a form of PLGA MS was markedly transported into AM phi at an amount 10 times greater than that for the free RFP powder. However, a large proportion of RFP was eliminated from the lungs by 6 h after insufflation. (C) 2013 Elsevier B.V. All rights reserved.
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