Abstract
In this study we develop a new biodegradable and biocompatible nanocarrier to improve the lung biodistribution and minimize systemic side effects of pulmonary administered drugs.
To obtain cationic NCs (Cy5/PLGA+), the formulation was done by mixing PLGA-Cy5 with PLGA-NH2 in a 1:1 ratio. For anionic NCs (Cy5/PLGA-), PLGA-NH2 was substituted with pristine PLGA. The colloidal stability of NCs was determined by analyzing their mean size dispersed in different culture and biological media. NCs cytotoxicity was evaluated on ATII cells by a MTT assay and their cellular uptake kinetics was monitored on THP-1 cell line by confocal microscopy. The in vivo biodistribution was studied by instilling male rats intratracheally with Cy5/PLGA- NCs. 5-μm sections of all lung lobes and liver were analyzed by confocal microscopy.
Cy5/PLGA+ and Cy5/PLGA- NCs were both colloidally stable in tested media and demonstrated to be biocompatible since viability tests did not show signs of cell toxicity. In addition, anionic and cationic NCs showed that at 4 hours of treatment almost the 90% of cells had internalized NCs. However, while the Cy5/PLGA- NCs increased their concentration in the cells over time, the Cy5/PLGA+ NCs' area within the cell remained stable up to 4h of treatment. In addition, we observed that the intratracheal administration of NCs allowed a homogeneous dispersion of the NCs throughout the lung, arriving to each lobe, without reaching the liver.
Footnotes
Cite this article as Eur Respir J 2022; 60: Suppl. 66, 2160.
This article was presented at the 2022 ERS International Congress, in session “-”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
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