Hara Kaori, Tsujimoto Hiroyuki, Tsukada Yusuke, Huang C C, Kawashima Yoshiaki, Tsutsumi Masahiro
Hosokawa Powder Technology Research Institute, 1-9, Shoudai, Tajika, Hirakata, Osaka 573-1132, Japan.
Int J Pharm. 2008 May 22;356(1-2):267-73. doi: 10.1016/j.ijpharm.2007.12.041. Epub 2008 Jan 8.
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.
聚乳酸-乙醇酸共聚物（PLGA）纳米球被报道为用于改善药物药理作用的有用肺部给药载体。本文描述了气管内滴注包裹药物的PLGA纳米球后组织的病理和组织学检查。将包裹异硫氰酸荧光素（FITC）的PLGA纳米球（分散在0.5 ml盐水中，然后与等体积空气混合）经气管内引入大鼠后，通过用该染料进行免疫组织化学染色证明，在大鼠的肺、肝、肾、脑、脾和胰腺中发现了FITC。在本研究中，气管内给予PLGA纳米球后，FITC在肺泡中至少停留1.5小时，但24小时后FITC几乎消失。此外，发现PLGA纳米球通过Ⅰ型肺泡上皮细胞立即（气管内给药后0.25小时内）被吸收进入血液。此外，发现PLGA纳米球对肺泡巨噬细胞和库普弗细胞等巨噬细胞的摄取具有抗性。结果表明，由于纳米球不被视为外来物质，因此由PLGA纳米球沉积引起的过度免疫反应导致组织损伤的可能性非常低。
