Modifying and integrating in vitro and ex vivo respiratory models for inhalation drug screening

Aylin Cidem, Peta Bradbury, Daniela Traini, Hui Xin Ong

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Article number581995
Pages (from-to)1-15
Number of pages15
JournalFrontiers in Bioengineering and Biotechnology
Volume8
DOIs
Publication statusPublished - 23 Oct 2020
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • drug efficacy
  • drug delivery
  • drug toxicity
  • inhalation therapy
  • isolated perfused lung
  • lung-on-chip
  • organoid
  • precision-cut lung slices

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