title: Distribution and deposition of respirable PLGA microspheres in lung alveoli.
abstract: 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 (AMφ) was determined by immunostaining for Mφ 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 AMφ cells up to 24h after insufflation. RFP in a form of PLGA MS was markedly transported into AMφ 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 6h after insufflation.
authors: Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
authors: Keiji
authors: K
authors: Hirota
authors: Tadafumi
authors: T
authors: Kawamoto
authors: Takehisa
authors: T
authors: Nakajima
authors: Kimiko
authors: K
authors: Makino
authors: Hiroshi
authors: H
authors: Terada
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000493:pharmacokinetics; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D003374:Coumarins / Q000008:administration & dosage / Q000493:pharmacokinetics; D005453:Fluorescence; D007124:Immunoenzyme Techniques; D019344:Lactic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008863:Microspheres; D010587:Phagocytosis / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics; D013844:Thiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014132:Trachea / Q000187:drug effects; D000097382:CD68 Molecule
chemical_list: D000904:Antibiotics, Antitubercular; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003374:Coumarins; D019344:Lactic Acid; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012293:Rifampin; D013844:Thiazoles; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C517282:coumarin 6