title: Preclinical safety and efficacy models for pulmonary drug delivery of antimicrobials with focus on in vitro models.
abstract: New pharmaceutical formulations must be proven as safe and effective before entering clinical trials. Also in the context of pulmonary drug delivery, preclinical models allow testing of novel antimicrobials, reducing risks and costs during their development. Such models allow reducing the complexity of the human lung, but still need to reflect relevant (patho-) physiological features. This review focuses on preclinical pulmonary models, mainly in vitro models, to assess drug safety and efficacy of antimicrobials. Furthermore, approaches to investigate common infectious diseases of the respiratory tract, are emphasized. Pneumonia, tuberculosis and infections occurring due to cystic fibrosis are in focus of this review. We conclude that especially in vitro models offer the chance of an efficient and detailed analysis of new antimicrobials, but also draw attention to the advantages and limitations of such currently available models and critically discuss the necessary steps for their future development.
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarbruecken/Helmholtz-Institute for Infection Research (HZI), Braunschweig, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Hittinger
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarbruecken/Helmholtz-Institute for Infection Research (HZI), Braunschweig, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Juntke
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarbruecken/Helmholtz-Institute for Infection Research (HZI), Braunschweig, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kletting
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarbruecken/Helmholtz-Institute for Infection Research (HZI), Braunschweig, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schneider-Daum
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarbruecken/Helmholtz-Institute for Infection Research (HZI), Braunschweig, Germany.
authors.forename: Cristiane
authors.initials: C
authors.lastname: de Souza Carvalho
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarbruecken/Helmholtz-Institute for Infection Research (HZI), Braunschweig, Germany; Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Campus, Building A4.1, Saarbruecken, Germany. Electronic address: Claus-Michael.Lehr@helmholtz-hzi.de.
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D023401:Animal Use Alternatives; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000382:microbiology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000009:adverse effects / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D066298:In Vitro Techniques; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents
keywords: 3R principle; A549; Alternatives to animal testing; Anti-infectives; Calu-3; Cell culture models; Cystic fibrosis; Disease-relevant models; Pneumonia; Tuberculosis