Modifying and Integrating in vitro and ex vivo Respiratory Models for Inhalation Drug Screening

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

doi:10.3389/fbioe.2020.581995

Cited by 37 publications

(26 citation statements)

References 104 publications

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“…When used for DPI deposition assessments, FPF performance is comparative to that of full NGI, and the FPD is comparative or better when using the FSI, depending on the drug tested [277]. While these impactors are an excellent way to test aerodynamic particle size distribution in the lungs, other aspects of the drug uptake, such as dissolution rate, transport through the epithelium, and therapeutic efficacy of the drugs, cannot be determined using standard impaction methods [278,279]. To address this issue, novel hybrid approaches and modifications have been developed, which involve marrying the biological representation of the lung epithelium with the impaction instrumentation.…”

Section: Methods To Assess Lung Deliverymentioning

confidence: 99%

“…These modified inserts can be customized to be inserted at various stages of the ACI for studies in both the upper and the lower respiratory regions of the lungs. By integrating the ALI culture models within the ACI, the deposition and subsequent permeability of formulations delivered with pMDIs and DPIs can be assessed with physiological relevance [ 279 , 287 , 288 ].…”

Section: Methods To Assess Lung Deliverymentioning

confidence: 99%

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Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract

Zhang

Almazi

Ong

et al. 2022

IJMS

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Since December 2019, a pandemic of COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread across the globe. At present, the Food and Drug Administration (FDA) has issued emergency approval for the use of some antiviral drugs. However, these drugs still have limitations in the specific treatment of COVID-19, and as such, new treatment strategies urgently need to be developed. RNA-interference-based gene therapy provides a tractable target for antiviral treatment. Ensuring cell-specific targeted delivery is important to the success of gene therapy. The use of nanoparticles (NPs) as carriers for the delivery of small interfering RNA (siRNAs) to specific tissues or organs of the human body could play a crucial role in the specific therapy of severe respiratory infections, such as COVID-19. In this review, we describe a variety of novel nanocarriers, such as lipid NPs, star polymer NPs, and glycogen NPs, and summarize the pre-clinical/clinical progress of these nanoparticle platforms in siRNA delivery. We also discuss the application of various NP-capsulated siRNA as therapeutics for SARS-CoV-2 infection, the challenges with targeting these therapeutics to local delivery in the lung, and various inhalation devices used for therapeutic administration. We also discuss currently available animal models that are used for preclinical assessment of RNA-interference-based gene therapy. Advances in this field have the potential for antiviral treatments of COVID-19 disease and could be adapted to treat a range of respiratory diseases.

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Section: Methods To Assess Lung Deliverymentioning

confidence: 99%

Section: Methods To Assess Lung Deliverymentioning

confidence: 99%

Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract

Zhang

Almazi

Ong

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Different culture conditions (hypoxia, microfluidics, ALI, and scaffolds) can be used. If the organoids are embedded in ECM, they form a lumen, and drug candidates can be microinjected into the construct [77]. Organoids, either generated from induced pluripotent stem cells or from primary cells isolated from patients, are an important tool for drug screening.…”

Section: Cellular Models For Lung Diseasesmentioning

confidence: 99%

Replacement Strategies for Animal Studies in Inhalation Testing

Frőhlich

2021

Sci

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Animal testing is mandatory in drug testing and is the gold standard for toxicity and efficacy evaluations. This situation is expected to change in the future as the 3Rs principle, which stands for the replacement, reduction, and refinement of the use of animals in science, is reinforced by many countries. On the other hand, technologies for alternatives to animal testing have increased. The need to develop and use alternatives depends on the complexity of the research topic and also on the extent to which the currently used animal models can mimic human physiology and/or exposure. The lung morphology and physiology of commonly used animal species differs from that of human lungs, and the realistic inhalation exposure of animals is challenging. In vitro and in silico methods can assess important aspects of the in vivo effects, namely particle deposition, dissolution, action at, and permeation through, the respiratory barrier, and pharmacokinetics. This review discusses the limitations of animal models and exposure systems and proposes in vitro and in silico techniques that could, when used together, reduce or even replace animal testing in inhalation testing in the future.

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“…Different culture conditions (hypoxia, microfluidics, ALI, scaffolds) can be used. If the organoids are embedded in extracellular matrix, they form a lumen and drug candidates can be microinjected into the construct [44]. Organoids either generated from induced pluripotent stem cells or from primary cells isolated from patients are an important tool for drug screening.…”

Section: Cellular Models For Lung Diseasesmentioning

confidence: 99%

Replacement Strategies for Animal Studies in Inhalation Testing

Frőhlich¹

2021

Preprint

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Testing in animals is mandatory in drug testing and the gold standard for evaluation of toxicity. This situation is expected to change in the future because the 3Rs principle, which stands for replacement, reduction and refinement of the use of animals in science, is reinforced by many countries. On the other hand, technologies for alternatives to animals experiments have increased. The necessity to develop and use of alternatives is influenced by the complexity of the research topic and also by the fact, to which extent the currently used animal models can mimic human physiology and/or exposure. Rodent lung morphology and physiology differs markedly for that of humans and inhalation exposure of the animals are challenging. In vitro and in silico methods can assess important aspects of the in vivo action, namely particle deposition, dissolution, action at and permeation across the respiratory barrier and pharmacokinetics. Out of the numerous homemade in vitro and in silico models some are available commercially or open access. This review discusses limitations of animal models and exposure systems and proposes a panel of in vitro and in silico techniques that, in the future, may replace animal experimentation in inhalation testing.

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Modifying and Integrating in vitro and ex vivo Respiratory Models for Inhalation Drug Screening

Cited by 37 publications

References 104 publications

Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract

Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract

Replacement Strategies for Animal Studies in Inhalation Testing

Replacement Strategies for Animal Studies in Inhalation Testing

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