Transport of Drugs through Biological Barriers—an Asset or Risk

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biopharmaceutics".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 3746

Special Issue Editors


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Guest Editor
Department of Analytical Chemistry, Faculty of Pharmacy, Medical University of Lodz, Łódź, Poland
Interests: QSAR; liquid chromatography; ADMET studies in silico and in vitro; environmental toxicology; spectroscopy
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Drug Research Program, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, 00790 Helsinki, Finland
Interests: transporters; permeability; blood-brain barrier; pharmacokinetics

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Guest Editor
Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Práter u. 50A, H-1083 Budapest, Hungary
Interests: drug-delivery; nose-to-brain delivery; transporters; dermal barrier; blood-brain barrier; lab-on-a-chip technology; Franz diffusion cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Drug transport across biological barriers in humans and animals plays a key role in drug delivery to a biological target. Insufficient drug transport is a serious obstacle to a drug’s intended activity.  In some cases, however, undesired compounds are absorbed through biological barriers (e.g., the skin, placenta or blood–brain barrier), posing a danger to humans and animals alike. 

This Special Issue primarily focuses on (but it is not limited to) the following:

  • In vivo, in vitro or in silico studies of drug transport through biological membranes;
  • Compound absorption from the gastro-intestinal tract, through skin or mucous membranes;
  • Pulmonary or ophthalmic absorption;
  • Transport of unwanted chemicals through the placenta or to mothers' milk;
  • Blood–brain barrier transport of xenobiotics;
  • Human and animal absorption of environmental contaminants via different routes;
  • Studies of compounds’ drug-likeness;
  • QSAR permeability studies;
  • Alternative drug delivery routes—novel methods or formulations.

Dr. Anna Sobańska
Dr. Heidi Kidron
Dr. Franciska Erdő
Guest Editors

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Keywords

  • ADMET studies
  • blood–brain barrier
  • gastro-intestinal absorption
  • placenta permeability
  • drug-likeness
  • skin/dermal absorption
  • drug delivery routes
  • compound transport across biological membranes
  • absorption of environmental contaminants
  • QSAR permeability studies

Published Papers (3 papers)

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Research

12 pages, 1025 KiB  
Article
ABCG2 Transports the Flukicide Nitroxynil and Affects Its Biodistribution and Secretion into Milk
by Laura Álvarez-Fernández, Esther Blanco-Paniagua and Gracia Merino
Pharmaceutics 2024, 16(4), 558; https://doi.org/10.3390/pharmaceutics16040558 - 19 Apr 2024
Viewed by 584
Abstract
The ABCG2 transporter plays a key role in pharmacological and toxicological processes, affecting bioavailability, tissue accumulation and milk secretion of its substrates. This protein is expressed in several biological barriers acting as a protective mechanism against xenobiotic exposure by pumping out a broad [...] Read more.
The ABCG2 transporter plays a key role in pharmacological and toxicological processes, affecting bioavailability, tissue accumulation and milk secretion of its substrates. This protein is expressed in several biological barriers acting as a protective mechanism against xenobiotic exposure by pumping out a broad range of compounds. However, its induced expression during lactation in alveolar cells of mammary gland represents a relevant route for active transport of unwanted chemicals into milk. This work aimed to characterize the involvement of ABCG2 in systemic exposure and milk secretion of the flukicide nitroxynil. Using MDCK–II cells overexpressing the transporter, we showed that nitroxynil is an in vitro substrate of different species variants of ABCG2. Moreover, using wild-type and Abcg2−/− mice, we showed that murine Abcg2 clearly affects plasma levels of nitroxynil. We also reported differences in nitroxynil accumulation in several tissues, with almost 2-fold higher concentration in kidney, small intestine and testis of Abcg2−/− mice. Finally, we proved that nitroxynil secretion into milk was also affected by Abcg2, with a 1.9-fold higher milk concentration in wild-type compared with Abcg2−/− mice. We conclude that ABCG2 significantly impacts nitroxynil biodistribution by regulating its passage across biological barriers. Full article
(This article belongs to the Special Issue Transport of Drugs through Biological Barriers—an Asset or Risk)
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19 pages, 1407 KiB  
Article
Transport of Non-Steroidal Anti-Inflammatory Drugs across an Oral Mucosa Epithelium In Vitro Model
by Grace C. Lin, Heinz-Peter Friedl, Sarah Grabner, Anna Gerhartl and Winfried Neuhaus
Pharmaceutics 2024, 16(4), 543; https://doi.org/10.3390/pharmaceutics16040543 - 15 Apr 2024
Viewed by 819
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most prescribed drugs to treat pain or fever. However, oral administration of NSAIDs is frequently associated with adverse effects due to their inhibitory effect on the constitutively expressed cyclooxygenase enzyme 1 (COX-1) in, for instance, [...] Read more.
Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most prescribed drugs to treat pain or fever. However, oral administration of NSAIDs is frequently associated with adverse effects due to their inhibitory effect on the constitutively expressed cyclooxygenase enzyme 1 (COX-1) in, for instance, the gastrointestinal tract. A systemic delivery, such as a buccal delivery, of NSAIDs would be beneficial and additionally has the advantage of a non-invasive administration route, especially favourable for children or the elderly. To investigate the transport of NSAIDs across the buccal mucosa and determine their potential for buccal therapeutic usage, celecoxib, diclofenac, ibuprofen and piroxicam were tested using an established oral mucosa Transwell® model based on human cell line TR146. Carboxyfluorescein and diazepam were applied as internal paracellular and transcellular marker molecule, respectively. Calculated permeability coefficients revealed a transport ranking of ibuprofen > piroxicam > diclofenac > celecoxib. Transporter protein inhibitor verapamil increased the permeability for ibuprofen, piroxicam and celecoxib, whereas probenecid increased the permeability for all tested NSAIDs. Furthermore, influence of local inflammation of the buccal mucosa on the transport of NSAIDs was mimicked by treating cells with a cytokine mixture of TNF-α, IL-1ß and IFN-γ followed by transport studies with ibuprofen (+ probenecid). Cellular response to pro-inflammatory stimuli was confirmed by upregulation of cytokine targets at the mRNA level, increased secreted cytokine levels and a significant decrease in the paracellular barrier. Permeability of ibuprofen was increased across cell layers treated with cytokines, while addition of probenecid increased permeability of ibuprofen in controls, but not across cell layers treated with cytokines. In summary, the suitability of the in vitro oral mucosa model to measure NSAID transport rankings was demonstrated, and the involvement of transporter proteins was confirmed; an inflammation model was established, and increased NSAID transport upon inflammation was measured. Full article
(This article belongs to the Special Issue Transport of Drugs through Biological Barriers—an Asset or Risk)
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15 pages, 5905 KiB  
Article
An Improved In Vitro Blood-Brain Barrier Model for the Evaluation of Drug Permeability Using Transwell with Shear Stress
by Junhyeong Kim, Seong-Ah Shin, Chang Sup Lee and Hye Jin Chung
Pharmaceutics 2024, 16(1), 48; https://doi.org/10.3390/pharmaceutics16010048 - 28 Dec 2023
Cited by 1 | Viewed by 1492
Abstract
The development of drugs targeting the central nervous system (CNS) is challenging because of the presence of the Blood-Brain barrier (BBB). Developing physiologically relevant in vitro BBB models for evaluating drug permeability and predicting the activity of drug candidates is crucial. The transwell [...] Read more.
The development of drugs targeting the central nervous system (CNS) is challenging because of the presence of the Blood-Brain barrier (BBB). Developing physiologically relevant in vitro BBB models for evaluating drug permeability and predicting the activity of drug candidates is crucial. The transwell model is one of the most widely used in vitro BBB models. However, this model has limitations in mimicking in vivo conditions, particularly in the absence of shear stress. This study aimed to overcome the limitations of the transwell model using immortalized human endothelial cells (hCMEC/D3) by developing a novel dish design for an orbital shaker, providing shear stress. During optimization, we assessed cell layer integrity using trans-endothelial electrical resistance measurements and the % diffusion of lucifer yellow. The efflux transporter activity and mRNA expression of junctional proteins (claudin-5, occludin, and VE-cadherin) in the newly optimized model were verified. Additionally, the permeability of 14 compounds was evaluated and compared with published in vivo data. The cell-layer integrity was substantially increased using the newly designed annular shaking-dish model. The results demonstrate that our model provided robust conditions for evaluating the permeability of CNS drug candidates, potentially improving the reliability of in vitro BBB models in drug development. Full article
(This article belongs to the Special Issue Transport of Drugs through Biological Barriers—an Asset or Risk)
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