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 1.5 h after the intratracheal administration of the PLGA nanospheres, but the FITC almost disappeared 24 h 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.