title: Histological examination of PLGA nanospheres for intratracheal drug administration.
abstract: Polylactide-glycolide (PLGA) nanospheres were reported as useful pulmonary drug delivery carriers for improving the pharmacological effect of drug. This paper describes the pathological and histological examinations of tissues after intratracheal instillation of drug encapsulated PLGA nanospheres. After intratracheally introducing FITC encapsulated PLGA nanospheres (dispersed in the 0.5 ml saline followed by mixing with an equal volume of air) to a rat, FITC was found existing in the rat's lungs, liver, kidney, brain, spleen and pancreas as demonstrated by immuno-histo-chemical staining with the dye. In this study, FITC stayed in alveoli at least for 1.5h after the intratracheal administration of the PLGA nanospheres, but the FITC almost disappeared 24h later. In addition, it was found that the PLGA nanospheres were absorbed in the blood immediately (within 0.25 h after the intratracheal administration) through the type 1 alveolar epithelium cell. Furthermore, the PLGA nanospheres were found resistant to uptake by macrophages such as alveolus macrophages and kupffer cells. The results showed that the possibility to induce tissue damage caused by the excessive immune response from the deposition of PLGA nanospheres was very low, because the nanospheres were not treated as foreign substances.
authors.affiliation: Hosokawa Powder Technology Research Institute, 1-9, Shoudai, Tajika, Hirakata, Osaka 573-1132, Japan. khara@hmc.hosokawa.com
authors.forename: Kaori
authors.initials: K
authors.lastname: Hara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsujimoto
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tsukada
authors.forename: C C
authors.initials: CC
authors.lastname: Huang
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsutsumi
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007150:Immunohistochemistry; D007728:Kupffer Cells / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D054118:Nanospheres; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011650:Pulmonary Alveoli / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016650:Fluorescein-5-isothiocyanate