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Toxicity of orally inhaled drug formulations at the alveolar barrier: parameters for initial biological screening
Oral delivery is the most common mode of systemic drug application. Inhalation is mainly used for local therapy of lung diseases but may also be a promising route for systemic delivery of drugs that have poor oral bioavailability. The thin alveolar barrier enables fast and efficient uptake of many m...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Taylor & Francis
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241192/ https://www.ncbi.nlm.nih.gov/pubmed/28574335 http://dx.doi.org/10.1080/10717544.2017.1333172 |
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author | Fröhlich, Eleonore |
author_facet | Fröhlich, Eleonore |
author_sort | Fröhlich, Eleonore |
collection | PubMed |
description | Oral delivery is the most common mode of systemic drug application. Inhalation is mainly used for local therapy of lung diseases but may also be a promising route for systemic delivery of drugs that have poor oral bioavailability. The thin alveolar barrier enables fast and efficient uptake of many molecules and could deliver small molecules and proteins, which are susceptible to degradation and show poor absorption by oral application. The low rate of biotransformation and proteolytic degradation increases bioavailability of drugs but accumulation of not absorbed material may impair normal lung function. This limitation is more relevant for compounds that should be systematically active because higher doses have to be applied to the lung. The review describes processes that determine absorption of orally inhaled formulations, namely dissolution in the lung lining fluid and uptake and degradation by alveolar epithelial cells and macrophages. Dissolution testing in simulated lung fluid, screening for cytotoxicity and pro-inflammatory action in respiratory cells and study of macrophage morphology, and phagocytosis can help to identify adverse effects of pulmonary formulations. |
format | Online Article Text |
id | pubmed-8241192 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-82411922021-07-08 Toxicity of orally inhaled drug formulations at the alveolar barrier: parameters for initial biological screening Fröhlich, Eleonore Drug Deliv Review Article Oral delivery is the most common mode of systemic drug application. Inhalation is mainly used for local therapy of lung diseases but may also be a promising route for systemic delivery of drugs that have poor oral bioavailability. The thin alveolar barrier enables fast and efficient uptake of many molecules and could deliver small molecules and proteins, which are susceptible to degradation and show poor absorption by oral application. The low rate of biotransformation and proteolytic degradation increases bioavailability of drugs but accumulation of not absorbed material may impair normal lung function. This limitation is more relevant for compounds that should be systematically active because higher doses have to be applied to the lung. The review describes processes that determine absorption of orally inhaled formulations, namely dissolution in the lung lining fluid and uptake and degradation by alveolar epithelial cells and macrophages. Dissolution testing in simulated lung fluid, screening for cytotoxicity and pro-inflammatory action in respiratory cells and study of macrophage morphology, and phagocytosis can help to identify adverse effects of pulmonary formulations. Taylor & Francis 2017-06-02 /pmc/articles/PMC8241192/ /pubmed/28574335 http://dx.doi.org/10.1080/10717544.2017.1333172 Text en © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Fröhlich, Eleonore Toxicity of orally inhaled drug formulations at the alveolar barrier: parameters for initial biological screening |
title | Toxicity of orally inhaled drug formulations at the alveolar barrier: parameters for initial biological screening |
title_full | Toxicity of orally inhaled drug formulations at the alveolar barrier: parameters for initial biological screening |
title_fullStr | Toxicity of orally inhaled drug formulations at the alveolar barrier: parameters for initial biological screening |
title_full_unstemmed | Toxicity of orally inhaled drug formulations at the alveolar barrier: parameters for initial biological screening |
title_short | Toxicity of orally inhaled drug formulations at the alveolar barrier: parameters for initial biological screening |
title_sort | toxicity of orally inhaled drug formulations at the alveolar barrier: parameters for initial biological screening |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241192/ https://www.ncbi.nlm.nih.gov/pubmed/28574335 http://dx.doi.org/10.1080/10717544.2017.1333172 |
work_keys_str_mv | AT frohlicheleonore toxicityoforallyinhaleddrugformulationsatthealveolarbarrierparametersforinitialbiologicalscreening |