Preclinical safety and efficacy models for pulmonary drug delivery of antimicrobials with focus on in vitro models

Hittinger, Marius; Juntke, Jenny; Kletting, Stephanie; Schneider-Daum, Nicole; Carvalho, Cristiane de Souza; Lehr, Claus‐Michael

doi:10.1016/j.addr.2014.10.011

Cited by 50 publications

(33 citation statements)

References 165 publications

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“…An overview of the available single-and multi-cell models of the lung is given elsewhere. (94,100,101) Recently, these cell culture models have matured into biomimetic models of the lung by incorporating previously neglected but crucial physiological aspects of the lung such as: 1) cultivation at the air-liquid interface with air on the apical side and liquid on the basal side of the epithelial barrier; (102,103) 2) growing the cells on biocompatible 3D (or 2D) matrices mimicking the elasticity of the pulmonary extracellular matrix; 3) exerting cyclic stretch on the cell layer simulating the mechanical strain profile experienced by the alveolar tissue during breathing activity; (104) and 4) combinations thereof. (105) FIG.…”

Section: Biological Models Of the Lungmentioning

confidence: 99%

“…(92) As an alternative a whole suite of ex vivo and cell-based in vitro models of the human and animal lung are available for medical science studies such as whole lung explants, lung tissue slices, cell cultures, or reconstructed lung tissue from primary lung cells as graphically summarized in Figure 3. (93,94) As all of these models (in vivo, ex vivo, in vitro) have their strengths and weaknesses, (95) scientists have to select the most suitable models depending on numerous aspects including relevance for the scientific issue to be addressed as well as model availability and cost of the study. (96) Reduced biological complexity of a model is typically associated with mitigated physiologic relevance, easier handling, and reduced economic burden.…”

Section: Biological Models Of the Lungmentioning

confidence: 99%

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Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung

Darquenne

Fleming

Katz

et al. 2016

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Development of a new drug for the treatment of lung disease is a complex and time consuming process involving numerous disciplines of basic and applied sciences. During the 2015 Congress of the International Society for Aerosols in Medicine, a group of experts including aerosol scientists, physiologists, modelers, imagers, and clinicians participated in a workshop aiming at bridging the gap between basic research and clinical efficacy of inhaled drugs. This publication summarizes the current consensus on the topic. It begins with a short description of basic concepts of aerosol transport and a discussion on targeting strategies of inhaled aerosols to the lungs. It is followed by a description of both computational and biological lung models, and the use of imaging techniques to determine aerosol deposition distribution (ADD) in the lung. Finally, the importance of ADD to clinical efficacy is discussed. Several gaps were identified between basic science and clinical efficacy. One gap between scientific research aimed at predicting, controlling, and measuring ADD and the clinical use of inhaled aerosols is the considerable challenge of obtaining, in a single study, accurate information describing the optimal lung regions to be targeted, the effectiveness of targeting determined from ADD, and some measure of the drug's effectiveness. Other identified gaps were the language and methodology barriers that exist among disciplines, along with the significant regulatory hurdles that need to be overcome for novel drugs and/or therapies to reach the marketplace and benefit the patient. Despite these gaps, much progress has been made in recent years to improve clinical efficacy of inhaled drugs. Also, the recent efforts by many funding agencies and industry to support multidisciplinary networks including basic science researchers, R&D scientists, and clinicians will go a long way to further reduce the gap between science and clinical efficacy.

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Section: Biological Models Of the Lungmentioning

confidence: 99%

Section: Biological Models Of the Lungmentioning

confidence: 99%

Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung

Darquenne

Fleming

Katz

et al. 2016

Journal of Aerosol Medicine and Pulmonary Drug Delivery

View full text Add to dashboard Cite

show abstract

“…In contrast to CF, there is currently no animal model of NCFB for the purpose of preliminary trials, despite its importance in characterising the fate of inhaled drugs [60]. In the case of NCFB, mimicking the lung is a challenge since the model has to address inflamed airways, mucus plugs, infection and bacterial biofilm [79]. An accurate preclinical model for NCFB will be valuable in proof-of-concept and preclinical testing of inhaled antibiotics, as well as preliminary PK/PD evaluation.…”

Section: Generalisability Of Study Resultsmentioning

confidence: 96%

Inhaled antibiotics in the treatment of non-cystic fibrosis bronchiectasis: clinical and drug delivery perspectives

Sugianto

Chan

2015

Expert Opinion on Drug Delivery

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The evidence base of the clinical efficacy of inhaled antibiotics in NCFB is limited and the degrees of reported clinical benefits have been modest and conflicting. Challenges surrounding inhaled antibiotics application and development include the lack of knowledge of disease factors and optimum management strategies, unreceptive lung pathophysiology and the lack of factors that support compliance and tolerability. Nonetheless, research continues to give birth to new clinical findings and novel formulations such as combination antibiotics and sustained-release formulations, which add great value to the development of efficacious, safe and convenient inhalable antibiotics of the future.

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“…The respiratory tract, being the most sensitive entry port of nanomaterials, has been the focus of several hundred in vitro and in vivo studies [for reviews see (28)(29)(30)]. Therefore, it is not surprising that human advanced in vitro models have been developed in order to gain more insight into the mode of action of inhalable aerosols/(nano)particles ( Figure 1A, B).…”

Section: Cell-based In Vitro Models: the Bottom Up Approachmentioning

confidence: 99%

In vitro-ex vivo model systems for nanosafety assessment

Wick

Chortarea

Guénat³

et al. 2015

European Journal of Nanomedicine

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Engineered nanomaterials have unique and novel properties enabling wide-ranging new applications in nearly all fields of research. As these new properties have raised concerns about potential adverse effects for the environment and human health, extensive efforts are underway to define reliable, cost-and time-effective, as well as mechanistic-based testing strategies to replace the current method of animal testing, which is still the most prevalent model used for the risk assessment of chemicals. Current approaches for nanomaterials follow this line. The aim of this review is to explore and qualify the relevance of new in vitro and ex vivo models in (nano) material safety assessment, a crucial prerequisite for translation into applications.

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Preclinical safety and efficacy models for pulmonary drug delivery of antimicrobials with focus on in vitro models

Cited by 50 publications

References 165 publications

Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung

Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung

Inhaled antibiotics in the treatment of non-cystic fibrosis bronchiectasis: clinical and drug delivery perspectives

In vitro-ex vivo model systems for nanosafety assessment

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