Pulmonary delivery and tissue distribution of aerosolized antisense 2'-O-Methyl RNA containing nanoplexes in the isolated perfused and ventilated rat lung

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
M DongSusanne Ammon-Treiber

Abstract

Pulmonary delivery of drugs, particularly in the treatment of lung cancer, is an attractive strategy for future targeted therapy. In this context, inhalation of nanoplexes might offer a new mode for drug delivery in gene therapy. However, limited data are currently available demonstrating pulmonary delivery, cellular uptake as well as local tolerability in lung tissue. The aim of this study was to elucidate the pulmonary delivery, tissue distribution and local tolerability of aerosolized chitosan-coated poly(lactide-co-glycolide) based nanoplexes containing antisense 2'-O-Methyl RNA (OMR). Therefore, an aerosol of OMR-nanoplexes or OMR alone was administered intra-tracheally using the model of the isolated perfused and ventilated rat lung. Localization of OMR in rat lung tissue was examined by immunohistochemistry. Administration of the OMR-nanoplex formulation resulted in significantly higher cellular OMR uptake of the respiratory epithelium in contrast to the administration of OMR alone, indicating that drug administration via aerosolized nanoplexes is able to target lung tissue. No prominent changes in lung physiology parameters were observed following inhalation, suggesting good local tolerability of OMR-nanoplex formulation.

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Citations

Feb 9, 2013·The Journal of Clinical Investigation·Lauren E MaysMichael S D Kormann
Jan 18, 2013·Therapeutic Delivery·Joanne M RamseySally-Ann Cryan
Mar 19, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Lisa M KaminskasChristopher J H Porter
Jan 25, 2020·Nanomaterials·Jorge F Pontes, Ana Grenha
Jun 21, 2013·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Ai-Zheng ChenDong-Liang Lin
Jul 21, 2016·Nanoscale·Nazrul Islam, Vito Ferro
Jul 4, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Zhengwei HuangChuanbin Wu

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