Applicability of RPMI 2650 and Calu-3 Cell Models for Evaluation of Nasal Formulations

Sibinovska, Nadica; Žakelj, Simon; Trontelj, Jurij; Kristan, Katja

doi:10.3390/pharmaceutics14020369

Cited by 20 publications

(20 citation statements)

References 46 publications

(80 reference statements)

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“…FL treatment on-chip was able to reduce expression of inflammation and epithelial damage-associated genes, however it could not recover barrier damage induced by PHMG. One reason could be the small treatment window of 24 h which was not sufficient to recover major loss of barrier integrity by PHMG or booster doses of inhaled FL might be required to overcome such major damage ( Kortekaas Krohn et al, 2019 ; Sibinovska et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

A multiplex inhalation platform to model in situ like aerosol delivery in a breathing lung-on-chip

et al. 2023

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Prolonged exposure to environmental respirable toxicants can lead to the development and worsening of severe respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD) and fibrosis. The limited number of FDA-approved inhaled drugs for these serious lung conditions has led to a shift from in vivo towards the use of alternative in vitro human-relevant models to better predict the toxicity of inhaled particles in preclinical research. While there are several inhalation exposure models for the upper airways, the fragile and dynamic nature of the alveolar microenvironment has limited the development of reproducible exposure models for the distal lung. Here, we present a mechanistic approach using a new generation of exposure systems, the Cloud α AX12. This novel in vitro inhalation tool consists of a cloud-based exposure chamber (VITROCELL) that integrates the breathing AXLung-on-chip system (AlveoliX). The ultrathin and porous membrane of the AX12 plate was used to create a complex multicellular model that enables key physiological culture conditions: the air-liquid interface (ALI) and the three-dimensional cyclic stretch (CS). Human-relevant cellular models were established for a) the distal alveolar-capillary interface using primary cell-derived immortalized alveolar epithelial cells (AXiAECs), macrophages (THP-1) and endothelial (HLMVEC) cells, and b) the upper-airways using Calu3 cells. Primary human alveolar epithelial cells (AXhAEpCs) were used to validate the toxicity results obtained from the immortalized cell lines. To mimic in vivo relevant aerosol exposures with the Cloud α AX12, three different models were established using: a) titanium dioxide (TiO2) and zinc oxide nanoparticles b) polyhexamethylene guanidine a toxic chemical and c) an anti-inflammatory inhaled corticosteroid, fluticasone propionate (FL). Our results suggest an important synergistic effect on the air-blood barrier sensitivity, cytotoxicity and inflammation, when air-liquid interface and cyclic stretch culture conditions are combined. To the best of our knowledge, this is the first time that an in vitro inhalation exposure system for the distal lung has been described with a breathing lung-on-chip technology. The Cloud α AX12 model thus represents a state-of-the-art pre-clinical tool to study inhalation toxicity risks, drug safety and efficacy.

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Section: Discussionmentioning

confidence: 99%

A multiplex inhalation platform to model in situ like aerosol delivery in a breathing lung-on-chip

et al. 2023

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“…However, they can be co-cultured with fibroblasts or endothelial cells, which can form a confluent monolayer and develop tight junctions as well. Thus, RPMI 2650 in a co-culture can be a reliable in vitro method for nasal drug absorption [92][93][94].…”

Section: Cell Culturementioning

confidence: 99%

Recent Options and Techniques to Assess Improved Bioavailability: In Vitro and Ex Vivo Methods

et al. 2023

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Bioavailability assessment in the development phase of a drug product is vital to reveal the disadvantageous properties of the substance and the possible technological interventions. However, in vivo pharmacokinetic studies provide strong evidence for drug approval applications. Human and animal studies must be designed on the basis of preliminary biorelevant experiments in vitro and ex vivo. In this article, the authors have reviewed the recent methods and techniques from the last decade that are in use for assessing the bioavailability of drug molecules and the effects of technological modifications and drug delivery systems. Four main administration routes were selected: oral, transdermal, ocular, and nasal or inhalation. Three levels of methodologies were screened for each category: in vitro techniques with artificial membranes; cell culture, including monocultures and co-cultures; and finally, experiments where tissue or organ samples were used. Reproducibility, predictability, and level of acceptance by the regulatory organizations are summarized for the readers.

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“…Sibinovska et al. (2022) concluded that these cell lines can be applied to investigate the permeation of drugs that is administered IN, for both local and systemic effects, and from solution‐ or suspension‐based formulations.…”

Section: Models To Determine Intranasal Systemic and Nose‐to‐brain Dr...mentioning

confidence: 99%

“…The Calu-3 and RPMI 2650 cells were cultured under ALI to determine if these cell models have the ability to detect differences in drug absorption from different types of formulations such as solution-and suspension-based formulations. Both these cell models demonstrated a sufficient ability to distinguish and to show the effect of formulation composition on the permeability of various drugs Sibinovska et al (2022). concluded that these cell lines can be applied to investigate the permeation of drugs that is administered IN, for both local and systemic effects, and from solution-or suspension-based formulations.The MDCK cell line can be transfected with human ABCG2, in order for the cell line to express breast cancer resistance protein (BCRP) to investigate the influence of the BCRP transporter on the permeation of different drugs Gonçalves et al (2021).…”

mentioning

confidence: 98%

In vitro and ex vivo experimental models for evaluation of intranasal systemic drug delivery as well as direct nose‐to‐brain drug delivery

Haasbroek‐Pheiffer

Niekerk

Kooy

et al. 2023

Biopharm & Drug Disp

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The intranasal route of administration provides a noninvasive method to deliver drugs into the systemic circulation and/or directly into the brain. Direct nose‐to‐brain drug delivery offers the possibility to treat central nervous system diseases more effectively, as it can evade the blood–brain barrier. In vitro and ex vivo intranasal models provide a means to investigate physiological and pharmaceutical factors that could play a role in drug delivery across the nasal epithelium as well as to determine the mechanisms involved in drug absorption from the nose. The development and implementation of cost‐effective pharmacokinetic models for intranasal drug delivery with good in vitro‐in vivo correlation can accelerate pharmaceutical drug product development and improve economic and ecological aspects by reducing the time and costs spent on animal studies. Special considerations should be made with regard to the purpose of the in vitro/ex vivo study, namely, whether it is intended to predict systemic or brain delivery, source and site of tissue or cell sampling, viability window of selected model, and the experimental setup of diffusion chambers. The type of model implemented should suit the relevant needs and requirements of the project, researcher, and interlaboratory. This review aims to provide an overview of in vitro and ex vivo models that have been developed to study intranasal and direct nose‐to‐brain drug delivery.

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Applicability of RPMI 2650 and Calu-3 Cell Models for Evaluation of Nasal Formulations

Cited by 20 publications

References 46 publications

A multiplex inhalation platform to model in situ like aerosol delivery in a breathing lung-on-chip

A multiplex inhalation platform to model in situ like aerosol delivery in a breathing lung-on-chip

Recent Options and Techniques to Assess Improved Bioavailability: In Vitro and Ex Vivo Methods

In vitro and ex vivo experimental models for evaluation of intranasal systemic drug delivery as well as direct nose‐to‐brain drug delivery

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