title: Toxicological perspectives of inhaled therapeutics and nanoparticles.
abstract: BACKGROUND
  The human respiratory system is an important route for the entry of inhaled therapeutics into the body to treat diseases. Inhaled materials may consist of gases, vapours, aerosols and particulates. In all cases, assessing the toxicological effect of inhaled therapeutics has many challenges.
  
  
  METHODS
  This article provides an overview of in vivo and in vitro models for testing the toxicity of inhaled therapeutics and nanoparticles implemented in drug delivery. Traditionally, inhalation toxicity has been performed on test animals to identify the median lethal concentration of airborne materials. Later maximum tolerable concentration denoted by LC0 has been introduced as a more ethically acceptable end point. More recently, in vitro methods have been developed, allowing the direct exposure of airborne material to cultured human target cells on permeable porous membranes at the air-liquid interface.
  
  
  CONCLUSIONS
  Modifications of current inhalation therapies, new pulmonary medications for respiratory diseases and implementation of the respiratory tract for systemic drug delivery are providing new challenges when conducting well-designed inhalation toxicology studies. In particular, the area of nanoparticles and nanocarriers is of critical toxicological concern. There is a need to develop toxicological test models, which characterise the toxic response and cellular interaction between inhaled particles and the respiratory system.
authors.affiliation: The University of New South Wales, School of Chemistry , UNSW Sydney, 2052 , Australia +61 403 028747 ; +61 2 9385 6141 ; a.hayes@unsw.edu.au.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Hayes
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Bakand
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D007928:Lethal Dose 50; D020714:Maximum Tolerated Dose; D008954:Models, Biological; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects*; D012137:Respiratory System / Q000187:drug effects / Q000503:physiopathology; D012140:Respiratory Tract Diseases / Q000188:drug therapy; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D000336:Aerosols
keywords: direct exposure methods; in vitro toxicity; inhalation therapy; inhalation toxicology; nanocarriers; nanomaterials; nanotoxicology; pulmonary drug delivery; therapeutics