Replacement Strategies for Animal Studies in Inhalation Testing

Frőhlich, Eleonore

doi:10.3390/sci3040045

Cited by 8 publications

(7 citation statements)

References 106 publications

(134 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A main feature in modeling respiratory epithelium using cell culture is the necessity for the air-liquid interface at the apical side of the monolayer. Hence, cells are grown on a membrane with the medium on one side of the membrane, i.e., the basolateral side, and the apical side exposed to air, often with oxygen concentrations [ 40 ]. This setup will facilitate polarized differentiation of the cells, formation of intercellular junctions, and expression of native proteins, including metabolizing enzymes [ 41 ].…”

Section: In Vitro Dissolution and Permeability Testing Methodsmentioning

confidence: 99%

“…Examples of tissue models that, according to their suppliers, have the barrier function and potential phenotype for drug delivery experiments are those developed commercially by Epithelix (MucilAir™ and SmallAir™) and MatTek 3D (EpiAirway™, EpiAirway-FT™, and EpiAlveolar™). A wider application of these can be seen in the literature for toxicity studies, while the applicability for drug delivery research is being investigated [ 40 ]. Furthermore, the authors of the current review article recommend referring to a recent review article published by Eedara et al (2022) where more examples of the absorption of orally inhaled drugs can be found [ 55 ].…”

Section: In Vitro Dissolution and Permeability Testing Methodsmentioning

confidence: 99%

See 1 more Smart Citation

In Vitro Dissolution and Permeability Testing of Inhalation Products: Challenges and Advances

2023

View full text Add to dashboard Cite

In vitro dissolution and permeability testing aid the simulation of the in vivo behavior of inhalation drug products. Although the regulatory bodies have specific guidelines for the dissolution of orally administered dosage forms (e.g., tablets and capsules), this is not the case for orally inhaled formulations, as there is no commonly accepted test for assessing their dissolution pattern. Up until a few years ago, there was no consensus that assessing the dissolution of orally inhaled drugs is a key factor in the assessment of orally inhaled products. With the advancement of research in the field of dissolution methods for orally inhaled products and a focus on systemic delivery of new, poorly water-soluble drugs at higher therapeutic doses, an evaluation of dissolution kinetics is proving crucial. Dissolution and permeability testing can determine the differences between the developed formulations and the innovator’s formulations and serve as a useful tool in correlating in vitro and in vivo studies. The current review highlights recent advances in the dissolution and permeability testing of inhalation products and their limitations, including recent cell-based technology. Although a few new dissolution and permeability testing methods have been established that have varying degrees of complexity, none have emerged as the standard method of choice. The review discusses the challenges of establishing methods that can closely simulate the in vivo absorption of drugs. It provides practical insights into method development for various dissolution testing scenarios and challenges with dose collection and particle deposition from inhalation devices for dissolution tests. Furthermore, dissolution kinetic models and statistical tests to compare the dissolution profiles of test and reference products are discussed.

show abstract

Section: In Vitro Dissolution and Permeability Testing Methodsmentioning

confidence: 99%

Section: In Vitro Dissolution and Permeability Testing Methodsmentioning

confidence: 99%

In Vitro Dissolution and Permeability Testing of Inhalation Products: Challenges and Advances

2023

View full text Add to dashboard Cite

show abstract

“…Respiratory diseases are globally among the most common diseases, especially chronic obstructive pulmonary disease (COPD) and asthma ( 2 ). COPD and asthma together with cystic fibrosis (CF) have been identified as the third leading cause of death worldwide ( 4 , 5 ). Acute respiratory infections can induce pneumonia, either through community- or hospital-acquired pathogens or through inflammation induced by prolonged mechanical ventilation.…”

Section: Introductionmentioning

confidence: 99%

“…cystic fibrosis (CF) have been identified as the third leading cause of death worldwide (4,5). Acute respiratory infections can induce pneumonia, either through community-or hospital-acquired pathogens or through inflammation induced by prolonged mechanical ventilation.…”

mentioning

confidence: 99%

A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

Bohländer

2023

Front. Immunol.

View full text Add to dashboard Cite

Inflammatory lung diseases represent a persistent burden for patients and the global healthcare system. The combination of high morbidity, (partially) high mortality and limited innovations in the last decades, have resulted in a great demand for new therapeutics. Are therapeutic IgA antibodies possibly a new hope in the treatment of inflammatory lung diseases? Current research increasingly unravels the elementary functions of IgA as protector against infections and as modulator of overwhelming inflammation. With a focus on IgA, this review describes the pathological alterations in mucosal immunity and how they contribute to chronic inflammation in the most common inflammatory lung diseases. The current knowledge of IgA functions in the circulation, and particularly in the respiratory mucosa, are summarized. The interplay between neutrophils and IgA seems to be key in control of inflammation. In addition, the hurdles and benefits of therapeutic IgA antibodies, as well as the currently known clinically used IgA preparations are described. The data highlighted here, together with upcoming research strategies aiming at circumventing the current pitfalls in IgA research may pave the way for this promising antibody class in the application of inflammatory lung diseases.

show abstract

“…It is therefore crucial, in accordance with the reinforcement of the 3Rs (replace, refine, and reuse), rule, to favor alternative NHP aerosol models [ 16 ] before experimentation on living NHPs, such as macaques. One attractive possibility is to use an in vitro replica of the NHP respiratory system.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Aerosol Deposition Between a Cynomolgus Macaque and a 3D Printed Cast Model of the Animal

et al. 2023

View full text Add to dashboard Cite

Purpose Preclinical aerosol studies using animals are essential for evaluating toxic or therapeutic effects on human respiratory tract. Macaques are relevant animal models for respiratory studies, but they are sensitive, expensive and difficult-to-access. Methods In the context of preliminary studies before animal experiments, we set up an alternative in vitro anatomical model of macaque airways to reduce, refine and replace (3Rs) the animals. We printed an in vitro anatomical cast until the third bronchial division from X-ray computed tomography data of a healthy cynomolgus macaque. This in vitro model was then connected to a respiratory pump to mimic macaque’s breathing. We assessed the relevance of this in vitro model, by comparing aerosol deposition patterns obtained with the anatomical model and in three macaques using planar gamma camera imaging. DTPA- 99m Technetium aerosols were produced using three jet nebulizers, generating three different particle sizes: 13.1, 3.2 and 0.93 µm in terms of the mass median aerodynamic diameter (MMAD). Results The data showed no statistical differences between the animal and anatomical in vitro models in terms of total aerosol deposited in the airways. However, the distribution of the deposition in the airways showed a higher deposited fraction in the upper respiratory tract in the animals than the in vitro model for all particle sizes . Conclusions The anatomical printed model appears to be a relevant in vitro tool to predict total aerosol deposition in macaque airways.

show abstract

Replacement Strategies for Animal Studies in Inhalation Testing

Cited by 8 publications

References 106 publications

In Vitro Dissolution and Permeability Testing of Inhalation Products: Challenges and Advances

In Vitro Dissolution and Permeability Testing of Inhalation Products: Challenges and Advances

A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

Comparison of Aerosol Deposition Between a Cynomolgus Macaque and a 3D Printed Cast Model of the Animal

Contact Info

Product

Resources

About