PMID- 33195144 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201117 IS - 2296-4185 (Print) IS - 2296-4185 (Electronic) IS - 2296-4185 (Linking) VI - 8 DP - 2020 TI - Modifying and Integrating in vitro and ex vivo Respiratory Models for Inhalation Drug Screening. PG - 581995 LID - 10.3389/fbioe.2020.581995 [doi] LID - 581995 AB - For the past 50 years, the route of inhalation has been utilized to administer therapies to treat a variety of respiratory and pulmonary diseases. When compared with other drug administration routes, inhalation offers a targeted, non-invasive approach to deliver rapid onset of drug action to the lung, minimizing systemic drug exposure and subsequent side effects. However, despite advances in inhaled therapies, there is still a need to improve the preclinical screening and the efficacy of inhaled therapeutics. Innovative in vitro models of respiratory physiology to determine therapeutic efficacy of inhaled compounds have included the use of organoids, micro-engineered lung-on-chip systems and sophisticated bench-top platforms to enable a better understanding of pulmonary mechanisms at the molecular level, rapidly progressing inhaled therapeutic candidates to the clinic. Furthermore, the integration of complementary ex vivo models, such as precision-cut lung slices (PCLS) and isolated perfused lung platforms have further advanced preclinical drug screening approaches by providing in vivo relevance. In this review, we address the challenges and advances of in vitro models and discuss the implementation of ex vivo inhaled drug screening models. Specifically, we address the importance of understanding human in vivo pulmonary mechanisms in assessing strategies of the preclinical screening of drug efficacy, toxicity and delivery of inhaled therapeutics. CI - Copyright (c) 2020 Cidem, Bradbury, Traini and Ong. FAU - Cidem, Aylin AU - Cidem A AD - Respiratory Technology, Woolcock Institute of Medical Research, Sydney, NSW, Australia. FAU - Bradbury, Peta AU - Bradbury P AD - Respiratory Technology, Woolcock Institute of Medical Research, Sydney, NSW, Australia. AD - Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia. FAU - Traini, Daniela AU - Traini D AD - Respiratory Technology, Woolcock Institute of Medical Research, Sydney, NSW, Australia. AD - Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia. FAU - Ong, Hui Xin AU - Ong HX AD - Respiratory Technology, Woolcock Institute of Medical Research, Sydney, NSW, Australia. AD - Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia. LA - eng PT - Journal Article PT - Review DEP - 20201023 PL - Switzerland TA - Front Bioeng Biotechnol JT - Frontiers in bioengineering and biotechnology JID - 101632513 PMC - PMC7644812 OTO - NOTNLM OT - drug delivery OT - drug efficacy OT - drug toxicity OT - inhalation therapy OT - isolated perfused lung OT - lung-on-chip OT - organoid OT - precision-cut lung slices EDAT- 2020/11/17 06:00 MHDA- 2020/11/17 06:01 PMCR- 2020/01/01 CRDT- 2020/11/16 08:54 PHST- 2020/07/10 00:00 [received] PHST- 2020/10/06 00:00 [accepted] PHST- 2020/11/16 08:54 [entrez] PHST- 2020/11/17 06:00 [pubmed] PHST- 2020/11/17 06:01 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fbioe.2020.581995 [doi] PST - epublish SO - Front Bioeng Biotechnol. 2020 Oct 23;8:581995. doi: 10.3389/fbioe.2020.581995. eCollection 2020.