In Vitro Modeling of Idiopathic Pulmonary Fibrosis: Lung-on-a-Chip Systems and Other 3D Cultures

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(21), С. 11751 - 11751

Опубликована: Ноя. 1, 2024

Idiopathic pulmonary fibrosis (IPF) is a lethal disorder characterized by relentless progression of lung that causes respiratory failure and early death. Currently, no curative treatments are available, existing therapies include limited selection antifibrotic agents only slow disease progression. The development novel therapeutics has been hindered understanding the disease's etiology pathogenesis. A significant challenge in developing new IPF lack vitro models accurately replicate crucial microenvironments. In response, three-dimensional (3D) have emerged as powerful tools for replicating organ-level microenvironments seen vivo. This review summarizes state art advanced 3D mimic many physiological pathological processes observed IPF. We begin with brief overview conventional models, such 2D cell cultures animal then explore more focusing on lung-on-a-chip systems. discuss current challenges future research opportunities this field, aiming to advance devices assess effectiveness treatments.

Язык: Английский

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Targeting biophysical microenvironment for improved treatment of chronic obstructive pulmonary disease

Trends in Molecular Medicine, Год журнала: 2023, Номер 29(11), С. 926 - 938

Опубликована: Сен. 11, 2023

Язык: Английский

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Aerosol delivery and spatiotemporal tissue distribution of hydroxychloroquine in rat lung

European Journal of Pharmaceutical Sciences, Год журнала: 2024, Номер 194, С. 106693 - 106693

Опубликована: Янв. 4, 2024

Inhalation enables the delivery of drugs directly to lung, increasing retention for prolonged exposure and maximizing therapeutic index. However, differential regional lung kinetics systemic pharmacokinetics are not fully known, their estimation is critical pulmonary drug delivery. The study evaluates hydroxychloroquine in different regions respiratory tract multiple routes administration. We also evaluated influence inhaled formulations on by identifying suitable nebulizers followed early characterization emitted aerosol physicochemical properties. salt- freebase-based required generated with An administration resulted varied pharmacokinetics, oral resulting low tissue concentrations all tract. A nose-only inhalation higher sustained a parenchyma-to-blood ratio 386 after 1440 min post-exposure. (i.e., nasal epithelium, larynx, trachea, bronchi, parenchyma) over time, indicating kinetics. spatiotemporal distribution due heterogeneity cell types, varying blood perfusion clearance mechanisms, deposition along In addition highlighting physiology, these results demonstrate ability retain increased levels lysosomotropic drugs. Such findings development future inhalation-based therapeutics, aiming optimize target site exposure, enable precision medicine, ultimately enhance clinical outcomes.

Язык: Английский

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Revolutionizing respiratory health research: “commercially-available lung-on-a-chip and air-liquid interface systems”

Frontiers in Lab on a Chip Technologies, Год журнала: 2024, Номер 3

Опубликована: Июнь 11, 2024

Inhalation of ultrafine particles, aerosol contaminants, and cigarette smoke can induce respiratory diseases. As humans are constantly exposed to various exogenous substances, it is crucial study their impacts on diseases airway dysfunction. Recently, organ-on-a-chip technology has been applied in many research studies understand disease mechanisms, drug screening, testing. The combination the air-liquid interface (ALI) culture method emerging as a new platform for realistically mimicking microenvironment physiological motions human lungs. Breathing motion be simulated through cyclic stretching, while blood flow replicated using channel within chip. ALI system critical mucociliary differentiation, pseudostratified morphology, epithelial barrier function development. systems allows integration stretch breathing microfluidic channels circulatory systems. chip also integrate lung cells, extracellular matrix, microstructures, providing microenvironments such fibroblast, collagen, immune cells cells. This review discusses effective tools recapitulating environments how they biological against pulmonary infections or inflammation, fibrosis, malignancy.

Язык: Английский

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Exposure-on-a-chip as a model for inhalation toxicology and pharmacology research

Elsevier eBooks, Год журнала: 2024, Номер unknown, С. 365 - 379

Опубликована: Янв. 1, 2024

Язык: Английский

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A stretchable human lung‐on‐chip model of alveolar inflammation for evaluating anti‐inflammatory drug response

Bioengineering & Translational Medicine, Год журнала: 2024, Номер 10(1)

Опубликована: Сен. 5, 2024

Abstract This study describes a complex human in vitro model for evaluating anti‐inflammatory drug response the alveoli that may contribute to reduction of animal testing pre‐clinical stage development. The is based on alveolar epithelial cell line Arlo co‐cultured with macrophages differentiated from THP‐1 line, creating physiological biological microenvironment. To mimic three‐dimensional architecture and dynamic expansion relaxation air‐blood‐barrier, they are grown stretchable microphysiological lung‐on‐chip. For validating model, three different protocols have been developed demonstrate clinically established effect glucocorticoids reduce certain inflammatory markers after pro‐inflammatory stimuli: (1) an inflammation caused by bacterial LPS (lipopolysaccharides) simulate LPS‐induced acute lung injury measured best cytokine IL‐6 release; (2) at ALI (air‐liquid interface) investigate aerosolized treatment, chemokine IL‐8 (3) combination cytokines TNFα IFNγ critical storm leading barrier disruption, where eventual weakening or protection can be measured. In all cases, presence appeared crucial mediating changes epithelium. induction led independently stretch conditions. Dynamic stretch, emulating breathing‐like mechanics, was essential modeling relevant outcome disruption upon TNFα/IFNγ‐induced inflammation.

Язык: Английский

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A Dynamic Breathing Lung Chip for Precise Evaluation of Inhaled Drug Efficacy and Airway Epithelial Responses

ACS Biomaterials Science & Engineering, Год журнала: 2024, Номер 11(1), С. 682 - 691

Опубликована: Дек. 1, 2024

Inhaled therapy has become a crucial treatment option for respiratory diseases like asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD), delivering drugs directly to bronchial alveolar tissues. However, traditional static in vitro cell models, while valuable studying pharmacokinetics (PK) pharmacodynamics (PD), fall short replicating the dynamic nature of physiological breathing. In this study, we present breathing lung chip model that integrates mechanism with an air-liquid interface (ALI) culture environment overcome these limitations. The platform replicates key aspects physiology, including functional airway interface, cyclic motion, medium circulation. Using Calu-3 line epithelium, our experiments show incorporation motion significantly enhances efficacy inhaled drug delivery cellular uptake, resulting improved outcomes compared direct exposure drug. While further research is needed explore its full potential, holds promise advancing screening research.

Язык: Английский

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Strategies for overcoming the biological barriers associated with the administration of inhaled monoclonal antibodies for lung diseases

Expert Opinion on Drug Delivery, Год журнала: 2023, Номер 20(8), С. 1085 - 1095

Опубликована: Авг. 3, 2023

ABSTRACTIntroduction Monoclonal antibodies (mAbs) should be administered by inhalation rather than parenterally to improve their efficiency in lung diseases. However, the pulmonary administration of mAbs terms aerosol technology and formulation for is difficult.Areas covered The feasible or suitable strategies overcoming barriers associated with administering are described.Expert opinion Providing via individuals disorders still difficult. a desirable method mAb delivery. Inhaled production needs well thought out. illness, patient group(s), therapeutic molecule selected, its interaction biological lungs, formulation, excipients, systems must all thoroughly investigated. Therefore, create inhaled that stable efficacious, it will essential examine problems linked instability protein aggregation. More excipients also need manufactured, expanding range design choices. Another crucial requirement novel carriers topical delivery lungs since might significantly enhance proteins’ stability pharmacokinetic profile.KEYWORDS: antibodiesinhalation routebiological barriersinhalersformulation Article highlights In several experimental situations, achieve better response when given route supplied systemically.Direct high local doses offers advantage achieving equivalence considerably higher systemically parenteral methods.The complex because they macromolecules.Several anatomical, physiological, immunological influence effectiveness biologics delivery.Selecting appropriate other parameters deliver fundamental need.The absorption disposition each being considered use studied individually there insufficient knowledge make accurate predictions currently available data.Declaration interestThe authors have no relevant affiliations financial involvement any organization entity interest conflict subject matter materials discussed manuscript. This includes employment, consultancies, honoraria, stock ownership options, expert testimony, grants patents received pending, royalties.Reviewer disclosuresPeer reviewers on this manuscript relationships disclose.Additional informationFundingThis paper was not funded.

Язык: Английский

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Intermediate phase engineering towards efficient and stable perovskite solar cells: Principles and strategies

Materials Today Communications, Год журнала: 2023, Номер 37, С. 107147 - 107147

Опубликована: Сен. 19, 2023

Язык: Английский

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Advances in In Vitro Blood-Air Barrier Models and the Use of Nanoparticles in COVID-19 Research

Tissue Engineering Part B Reviews, Год журнала: 2023, Номер 30(1), С. 82 - 96

Опубликована: Авг. 19, 2023

Respiratory infections caused by coronaviruses (CoVs) have become a major public health concern in the past two decades as revealed emergence of SARS-CoV 2002, MERS-CoV 2012, and SARS-CoV-2 2019. The most severe clinical phenotypes commonly arise from exacerbation immune response following infection alveolar epithelial cells localized at pulmonary blood-air barrier. Preclinical rodent models do not adequately represent essential genetic properties barrier, thus necessitating use humanized transgenic models. However, existing monolayer cell culture so far been unable to mimic complex lung microenvironment. In this respect, air–liquid interface models, tissue engineered organ-on-a-chip systems, which aim better imitate site microenvironment microphysiology, are being developed replace used their is becoming more widespread every day. On contrary, studies on development nanoparticles (NPs) that respiratory viruses, those NPs therapy progressing rapidly. first part review describes vitro plays central role COVID-19 progression. second review, mimicking virus and/or designed carry therapeutic agents explained exemplified. pandemic highlighted urgent need gain deeper understanding viral pathogenesis develop approaches for rapid translation research findings vaccines or therapeutics will protect future pandemics. Numerous progress worldwide but advanced accurately natural still under development. This aims introduce brief summary features currently be improved, especially researchers working field regenerative medicine nanotechnology.

Язык: Английский

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