Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.9
4.9
Journals
Pharmaceutics
Special Issues
Fate of Drugs and Delivery Systems in the Lungs
share announcement

Fate of Drugs and Delivery Systems in the Lungs

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 13989

Special Issue Editor

Dr. Cynthia Bosquillon

E-Mail Website
Guest Editor
School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK
Interests: pulmonary drug delivery; biopharmaceutics; in vitro models; drug transport mechanisms; drug transporters; pro-drugs

Special Issue Information

Dear Colleagues,

Delivering drugs directly to the lungs remains a major therapeutic intervention in the management of respiratory diseases. In addition, thanks to the advantageous characteristics of the pulmonary tissue, drug inhalation has more recently been explored as a non-invasive route to the systemic circulation, particularly for drugs with a poor oral bioavailability.

The primary focus in inhalation research has been on improving drug formulations and inhaler technologies in order to enhance drug deposition in the lungs. Recent years have seen the development of advanced delivery systems to enable the administration of biotherapeutics to the respiratory tract, target specific cells of the pulmonary tissue, or prolong drug retention in the lungs. The fate of drugs and drug formulations once deposited in the lungs has, in comparison, received little attention. This can partly be explained by the anatomical complexity of the lungs, and, consequently, the need for simplified tools to investigate drug disposition post-inhalation.

This Special Issue will highlight current research exploring the events that follow the deposition of drugs and delivery systems at the surface of the lungs, including, but not limited to, particle dissolution, interactions with cellular and non-cellular pulmonary barriers, epithelial transport, intracellular trafficking, and the development of in vitro systems to study those events.

Dr. Cynthia Bosquillon
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pulmonary delivery
  • transport mechanisms
  • intracellular uptake
  • cellular and sub-cellular trafficking
  • particle dissolution
  • nanocarriers
  • biotherapeutics
  • mucus as a barrier
  • in vitro models

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (4 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

15 pages, 4691 KiB  
Article
Investigating the Suitability of High Content Image Analysis as a Tool to Assess the Reversibility of Foamy Alveolar Macrophage Phenotypes In Vitro
by Ewelina Hoffman, Darragh Murnane and Victoria Hutter
Pharmaceutics 2020, 12(3), 262; https://doi.org/10.3390/pharmaceutics12030262 - 13 Mar 2020
Cited by 4 | Viewed by 3085
Abstract
Many potential inhaled medicines fail during development due to the induction of a highly vacuolated or “foamy” alveolar macrophage phenotype response in pre-clinical studies. There is limited understanding if this response to an inhaled stimulus is adverse or adaptive, and additionally if it [...] Read more.
Many potential inhaled medicines fail during development due to the induction of a highly vacuolated or “foamy” alveolar macrophage phenotype response in pre-clinical studies. There is limited understanding if this response to an inhaled stimulus is adverse or adaptive, and additionally if it is a transient or irreversible process. The aim of this study was to evaluate whether high content image analysis could distinguish between different drug-induced foamy macrophage phenotypes and to determine the extent of the reversibility of the foamy phenotypes by assessing morphological changes over time. Alveolar-like macrophages derived from the human monocyte cell line U937 were exposed for 24 h to compounds known to induce a foamy macrophage phenotype (amiodarone, staurosporine) and control compounds that are not known to cause a foamy macrophage phenotype in vitro (fluticasone and salbutamol). Following drug stimulation, the cells were rested in drug-free media for the subsequent 24 or 48 h. Cell morphometric parameters (cellular and nuclear area, vacuoles numbers and size) and phospholipid content were determined using high content image analysis. The foamy macrophage recovery was dependent on the mechanism of action of the inducer compound. Amiodarone toxicity was associated with phospholipid accumulation and morphometric changes were reversed when the stimulus was removed from culture environment. Conversely cells were unable to recover from exposure to staurosporine which initiates the apoptosis pathway. This study shows that high content analysis can discriminate between different phenotypes of foamy macrophages and may contribute to better decision making in the process of new drug development. Full article
(This article belongs to the Special Issue Fate of Drugs and Delivery Systems in the Lungs)
►▼ Show Figures

Figure 1

15 pages, 2461 KiB  
Article
Development of an In Vitro System to Study the Interactions of Aerosolized Drugs with Pulmonary Mucus
by Safar Alqahtani, Clive J. Roberts, Snjezana Stolnik and Cynthia Bosquillon
Pharmaceutics 2020, 12(2), 145; https://doi.org/10.3390/pharmaceutics12020145 - 11 Feb 2020
Cited by 9 | Viewed by 3506
Abstract
Mucus is the first biological component inhaled drugs encounter on their journey towards their pharmacological target in the upper airways. Yet, how mucus may influence drug disposition and efficacy in the lungs has been essentially overlooked. In this study, a simple in vitro [...] Read more.
Mucus is the first biological component inhaled drugs encounter on their journey towards their pharmacological target in the upper airways. Yet, how mucus may influence drug disposition and efficacy in the lungs has been essentially overlooked. In this study, a simple in vitro system was developed to investigate the factors promoting drug interactions with airway mucus in physiologically relevant conditions. Thin layers of porcine tracheal mucus were prepared in Transwell® inserts and initially, the diffusion of various fluorescent dyes across those layers was monitored over time. A deposition system featuring a MicroSprayer® aerosolizer was optimized to reproducibly deliver liquid aerosols to multiple air-facing layers and then exploited to compare the impact of airway mucus on the transport of inhaled bronchodilators. Both the dyes and drugs tested were distinctly hindered by mucus with high logP compounds being the most affected. The diffusion rate of the bronchodilators across the layers was in the order: ipratropium ≈ glycopyronnium > formoterol > salbutamol > indacaterol, suggesting hydrophobicity plays an important role in their binding to mucus but is not the unique parameter involved. Testing of larger series of compounds would nevertheless be necessary to better understand the interactions of inhaled drugs with airway mucus. Full article
(This article belongs to the Special Issue Fate of Drugs and Delivery Systems in the Lungs)
►▼ Show Figures

Figure 1

12 pages, 767 KiB  
Article
Pulmonary Metabolism of Substrates for Key Drug-Metabolizing Enzymes by Human Alveolar Type II Cells, Human and Rat Lung Microsomes, and the Isolated Perfused Rat Lung Model
by Katarina Rubin, Pär Ewing, Erica Bäckström, Anna Abrahamsson, Britta Bonn, Satoshi Kamata and Ken Grime
Pharmaceutics 2020, 12(2), 117; https://doi.org/10.3390/pharmaceutics12020117 - 1 Feb 2020
Cited by 13 | Viewed by 3291
Abstract
Significant pulmonary metabolism of inhaled drugs could have drug safety implications or influence pharmacological effectiveness. To study this in vitro, lung microsomes or S9 are often employed. Here, we have determined if rat and human lung microsomes are fit for purpose or whether [...] Read more.
Significant pulmonary metabolism of inhaled drugs could have drug safety implications or influence pharmacological effectiveness. To study this in vitro, lung microsomes or S9 are often employed. Here, we have determined if rat and human lung microsomes are fit for purpose or whether it is better to use specific cells where drug-metabolizing enzymes are concentrated, such as alveolar type II (ATII) cells. Activities for major hepatic and pulmonary human drug-metabolizing enzymes are assessed and the data contextualized towards an in vivo setting using an ex vivo isolated perfused rat lung model. Very low rates of metabolism are observed in incubations with human ATII cells when compared to isolated hepatocytes and fewer of the substrates are found to be metabolized when compared to human lung microsomal incubations. Reactions selective for flavin-containing monooxygenases (FMOs), CYP1B1, CYP2C9, CYP2J2, and CYP3A4 all show significant rates in human lung microsomal incubations, but all activities are higher when rat lung microsomes are used. The work also demonstrates that a lung microsomal intrinsic clearance value towards the lower limit of detection for this parameter (3 µL/min/mg protein) results in a very low level of pulmonary metabolic clearance during the absorption period, for a drug dosed into the lung in vivo. Full article
(This article belongs to the Special Issue Fate of Drugs and Delivery Systems in the Lungs)
►▼ Show Figures

Figure 1

Review

Jump to: Research

24 pages, 945 KiB  
Review
Control of the Lung Residence Time of Highly Permeable Molecules after Nebulization: Example of the Fluoroquinolones
by Julien Brillault and Frédéric Tewes
Pharmaceutics 2020, 12(4), 387; https://doi.org/10.3390/pharmaceutics12040387 - 23 Apr 2020
Cited by 18 | Viewed by 3571
Abstract
Pulmonary drug delivery is a promising strategy to treat lung infectious disease as it allows for a high local drug concentration and low systemic side effects. This is particularly true for low-permeability drugs, such as tobramycin or colistin, that penetrate the lung at [...] Read more.
Pulmonary drug delivery is a promising strategy to treat lung infectious disease as it allows for a high local drug concentration and low systemic side effects. This is particularly true for low-permeability drugs, such as tobramycin or colistin, that penetrate the lung at a low rate after systemic administration and greatly benefit from lung administration in terms of the local drug concentration. However, for relatively high-permeable drugs, such as fluoroquinolones (FQs), the rate of absorption is so high that the pulmonary administration has no therapeutic advantage compared to systemic or oral administration. Formulation strategies have thus been developed to decrease the absorption rate and increase FQs’ residence time in the lung after inhalation. In the present review, some of these strategies, which generally consist of either decreasing the lung epithelium permeability or decreasing the release rate of FQs into the epithelial lining fluid after lung deposition, are presented in regards to their clinical aspects. Full article
(This article belongs to the Special Issue Fate of Drugs and Delivery Systems in the Lungs)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-4
Back to TopTop