Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.1
4.9
Journals
IJMS
Special Issues
Modelling Biological Barriers to Study Molecular Trafficking In Vitro: Advances...
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Modelling Biological Barriers to Study Molecular Trafficking In Vitro: Advances and Applications

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 19343

Special Issue Editors

Dr. Manuela Malatesta

E-Mail Website
Guest Editor
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37124 Verona, Italy
Interests: nanomedicine; regenerative medicine; cell imaging; ageing; muscle atrophy/dystrophy; antioxidant processes
Special Issues, Collections and Topics in MDPI journals
Dr. Flavia Carton

E-Mail Website
Guest Editor
Department of Neurosciences, Biomedicine and Movement Sciences, Anatomy and Histology Section, University of Verona, 37134 Verona, Italy
Interests: nanomaterials; nanoparticles formulation and characterization; drug delivery; cell culture; tissue engineering; biomaterilas; molecular biology; biological barriers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Understanding molecular traffic thought biological barriers is crucial for basic and applied research in several fields such as pharmaceutics, nanotechnology, pathology, physiology, toxicology, cosmetics, and food science. In recent years, a variety of in vitro models of biological barriers have been developed: the conventional two-dimensional cell monocultures have been complemented by three-dimensional co-cultures and organoids; to better mimic the barrier structure, bioengineered materials have been used to build matrices and scaffolds as a support for the cultured cells; bioreactors and microfluidics have made it possible to simulate the complex physiological dynamics that occurs in vivo. These models have proved to be standardized, reliable, fast, cost effective and ethically preferable, and allowed investigating how molecules may move through several types of barriers, such as the skin, cornea, intestinal mucosa, airway epithelium, renal epithelium, blood–brain and blood–placental barrier, and others.

This Special Issue is aimed at illustrating the great contribution of in vitro biological barriers to the knowledge of the trans-barrier molecular trafficking in vivo, as well as at presenting novel biological barrier models designed for permeability studies. All related deep molecular research is welcome and in vivo verification experiments are highly encouraged.

We invite researchers of all the relevant fields—bioengineering, biology, biotechnology, chemistry, pharmacology, biophysics, etc.—to present their results and commentaries by contributing original research articles or review papers.  

Prof. Manuela Malatesta
Dr. Flavia Carton
Guest Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • barrier permeability
  • cell culture
  • biomaterials
  • bioreactor
  • microfluidics

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 (5 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

26 pages, 14853 KiB  
Article
An Innovative Fluid Dynamic System to Model Inflammation in Human Skin Explants
by Andrea Galvan, Enrica Cappellozza, Yann Pellequer, Anita Conti, Edoardo Dalla Pozza, Enrico Vigato, Manuela Malatesta and Laura Calderan
Int. J. Mol. Sci. 2023, 24(7), 6284; https://doi.org/10.3390/ijms24076284 - 27 Mar 2023
Cited by 2 | Viewed by 2170
Abstract
Skin is a major administration route for drugs, and all transdermal formulations must be tested for their capability to overcome the cutaneous barrier. Therefore, developing highly reliable skin models is crucial for preclinical studies. The current in vitro models are unable to replicate [...] Read more.
Skin is a major administration route for drugs, and all transdermal formulations must be tested for their capability to overcome the cutaneous barrier. Therefore, developing highly reliable skin models is crucial for preclinical studies. The current in vitro models are unable to replicate the living skin in all its complexity; thus, to date, excised human skin is considered the gold standard for in vitro permeation studies. However, skin explants have a limited life span. In an attempt to overcome this problem, we used an innovative bioreactor that allowed us to achieve good structural and functional preservation in vitro of explanted human skin for up to 72 h. This device was then used to set up an in vitro inflammatory model by applying two distinct agents mimicking either exogenous or endogenous stimuli: i.e., dithranol, inducing the contact dermatitis phenotype, and the substance P, mimicking neurogenic inflammation. Our in vitro system proved to reproduce inflammatory events observed in vivo, such as vasodilation, increased number of macrophages and mast cells, and increased cytokine secretion. This bioreactor-based system may therefore be suitably and reliably used to simulate in vitro human skin inflammation and may be foreseen as a promising tool to test the efficacy of drugs and cosmetics. Full article
(This article belongs to the Special Issue Modelling Biological Barriers to Study Molecular Trafficking In Vitro: Advances and Applications)
►▼ Show Figures

Graphical abstract

21 pages, 3729 KiB  
Article
The Cultivation Modality and Barrier Maturity Modulate the Toxicity of Industrial Zinc Oxide and Titanium Dioxide Nanoparticles on Nasal, Buccal, Bronchial, and Alveolar Mucosa Cell-Derived Barrier Models
by Helene Stuetz, Eva I. Reihs, Winfried Neuhaus, Maren Pflüger, Harald Hundsberger, Peter Ertl, Christian Resch, Gerald Bauer, Günter Povoden and Mario Rothbauer
Int. J. Mol. Sci. 2023, 24(6), 5634; https://doi.org/10.3390/ijms24065634 - 15 Mar 2023
Cited by 3 | Viewed by 2259
Abstract
As common industrial by-products, airborne engineered nanomaterials are considered important environmental toxins to monitor due to their potential health risks to humans and animals. The main uptake routes of airborne nanoparticles are nasal and/or oral inhalation, which are known to enable the transfer [...] Read more.
As common industrial by-products, airborne engineered nanomaterials are considered important environmental toxins to monitor due to their potential health risks to humans and animals. The main uptake routes of airborne nanoparticles are nasal and/or oral inhalation, which are known to enable the transfer of nanomaterials into the bloodstream resulting in the rapid distribution throughout the human body. Consequently, mucosal barriers present in the nose, buccal, and lung have been identified and intensively studied as the key tissue barrier to nanoparticle translocation. Despite decades of research, surprisingly little is known about the differences among various mucosa tissue types to tolerate nanoparticle exposures. One limitation in comparing nanotoxicological data sets can be linked to a lack of harmonization and standardization of cell-based assays, where (a) different cultivation conditions such as an air-liquid interface or submerged cultures, (b) varying barrier maturity, and (c) diverse media substitutes have been used. The current comparative nanotoxicological study, therefore, aims at analyzing the toxic effects of nanomaterials on four human mucosa barrier models including nasal (RPMI2650), buccal (TR146), alveolar (A549), and bronchial (Calu-3) mucosal cell lines to better understand the modulating effects of tissue maturity, cultivation conditions, and tissue type using standard transwell cultivations at liquid-liquid and air-liquid interfaces. Overall, cell size, confluency, tight junction localization, and cell viability as well as barrier formation using 50% and 100% confluency was monitored using trans-epithelial-electrical resistance (TEER) measurements and resazurin-based Presto Blue assays of immature (e.g., 5 days) and mature (e.g., 22 days) cultures in the presence and absence of corticosteroids such as hydrocortisone. Results of our study show that cellular viability in response to increasing nanoparticle exposure scenarios is highly compound and cell-type specific (TR146 6 ± 0.7% at 2 mM ZnO (ZnO) vs. ~90% at 2 mM TiO2 (TiO2) for 24 h; Calu3 93.9 ± 4.21% at 2 mM ZnO vs. ~100% at 2 mM TiO2). Nanoparticle-induced cytotoxic effects under air-liquid cultivation conditions declined in RPMI2650, A549, TR146, and Calu-3 cells (~0.7 to ~0.2-fold), with increasing 50 to 100% barrier maturity under the influence of ZnO (2 mM). Cell viability in early and late mucosa barriers where hardly influenced by TiO2 as well as most cell types did not fall below 77% viability when added to Individual ALI cultures. Fully maturated bronchial mucosal cell barrier models cultivated under ALI conditions showed less tolerance to acute ZnO nanoparticle exposures (~50% remaining viability at 2 mM ZnO for 24 h) than the similarly treated but more robust nasal (~74%), buccal (~73%), and alveolar (~82%) cell-based models. Full article
(This article belongs to the Special Issue Modelling Biological Barriers to Study Molecular Trafficking In Vitro: Advances and Applications)
►▼ Show Figures

Figure 1

21 pages, 4030 KiB  
Article
Ethosomal Gel for Topical Administration of Dimethyl Fumarate in the Treatment of HSV-1 Infections
by Mariaconcetta Sicurella, Walter Pula, Karolina Musiał, Katarzyna Cieślik-Boczula, Maddalena Sguizzato, Agnese Bondi, Markus Drechsler, Leda Montesi, Elisabetta Esposito and Peggy Marconi
Int. J. Mol. Sci. 2023, 24(4), 4133; https://doi.org/10.3390/ijms24044133 - 18 Feb 2023
Cited by 6 | Viewed by 3160
Abstract
The infections caused by the HSV-1 virus induce lesions on the lips, mouth, face, and eye. In this study, an ethosome gel loaded with dimethyl fumarate was investigated as a possible approach to treat HSV-1 infections. A formulative study was conducted, evaluating the [...] Read more.
The infections caused by the HSV-1 virus induce lesions on the lips, mouth, face, and eye. In this study, an ethosome gel loaded with dimethyl fumarate was investigated as a possible approach to treat HSV-1 infections. A formulative study was conducted, evaluating the effect of drug concentration on size distribution and dimensional stability of ethosomes by photon correlation spectroscopy. Ethosome morphology was investigated by cryogenic transmission electron microscopy, while the interaction between dimethyl fumarate and vesicles, and the drug entrapment capacity were respectively evaluated by FTIR and HPLC. To favor the topical application of ethosomes on mucosa and skin, different semisolid forms, based on xanthan gum or poloxamer 407, were designed and compared for spreadability and leakage. Dimethyl fumarate release and diffusion kinetics were evaluated in vitro by Franz cells. The antiviral activity against HSV-1 was tested by plaque reduction assay in Vero and HRPE monolayer cells, while skin irritation effect was evaluated by patch test on 20 healthy volunteers. The lower drug concentration was selected, resulting in smaller and longer stable vesicles, mainly characterized by a multilamellar organization. Dimethyl fumarate entrapment in ethosome was 91% w/w, suggesting an almost total recovery of the drug in the lipid phase. Xanthan gum 0.5%, selected to thicken the ethosome dispersion, allowed to control drug release and diffusion. The antiviral effect of dimethyl fumarate loaded in ethosome gel was demonstrated by a reduction in viral growth both 1 h and 4 h post-infection. Moreover, the patch test demonstrated the safety of the ethosomal gel applied on the skin. Full article
(This article belongs to the Special Issue Modelling Biological Barriers to Study Molecular Trafficking In Vitro: Advances and Applications)
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

33 pages, 752 KiB  
Review
Complexification of In Vitro Models of Intestinal Barriers, A True Challenge for a More Accurate Alternative Approach
by Michelle J. Haddad, Wendy Sztupecki, Carine Delayre-Orthez, Larbi Rhazi, Nicolas Barbezier, Flore Depeint and Pauline M. Anton
Int. J. Mol. Sci. 2023, 24(4), 3595; https://doi.org/10.3390/ijms24043595 - 10 Feb 2023
Cited by 16 | Viewed by 7472
Abstract
The use of cell models is common to mimic cellular and molecular events in interaction with their environment. In the case of the gut, the existing models are of particular interest to evaluate food, toxicants, or drug effects on the mucosa. To have [...] Read more.
The use of cell models is common to mimic cellular and molecular events in interaction with their environment. In the case of the gut, the existing models are of particular interest to evaluate food, toxicants, or drug effects on the mucosa. To have the most accurate model, cell diversity and the complexity of the interactions must be considered. Existing models range from single-cell cultures of absorptive cells to more complex combinations of two or more cell types. This work describes the existing solutions and the challenges that remain to be solved. Full article
(This article belongs to the Special Issue Modelling Biological Barriers to Study Molecular Trafficking In Vitro: Advances and Applications)
►▼ Show Figures

Figure 1

20 pages, 2595 KiB  
Review
In Vitro Models of Biological Barriers for Nanomedical Research
by Flavia Carton and Manuela Malatesta
Int. J. Mol. Sci. 2022, 23(16), 8910; https://doi.org/10.3390/ijms23168910 - 10 Aug 2022
Cited by 16 | Viewed by 2988
Abstract
Nanoconstructs developed for biomedical purposes must overcome diverse biological barriers before reaching the target where playing their therapeutic or diagnostic function. In vivo models are very complex and unsuitable to distinguish the roles plaid by the multiple biological barriers on nanoparticle biodistribution and [...] Read more.
Nanoconstructs developed for biomedical purposes must overcome diverse biological barriers before reaching the target where playing their therapeutic or diagnostic function. In vivo models are very complex and unsuitable to distinguish the roles plaid by the multiple biological barriers on nanoparticle biodistribution and effect; in addition, they are costly, time-consuming and subject to strict ethical regulation. For these reasons, simplified in vitro models are preferred, at least for the earlier phases of the nanoconstruct development. Many in vitro models have therefore been set up. Each model has its own pros and cons: conventional 2D cell cultures are simple and cost-effective, but the information remains limited to single cells; cell monolayers allow the formation of cell–cell junctions and the assessment of nanoparticle translocation across structured barriers but they lack three-dimensionality; 3D cell culture systems are more appropriate to test in vitro nanoparticle biodistribution but they are static; finally, bioreactors and microfluidic devices can mimicking the physiological flow occurring in vivo thus providing in vitro biological barrier models suitable to reliably assess nanoparticles relocation. In this evolving context, the present review provides an overview of the most representative and performing in vitro models of biological barriers set up for nanomedical research. Full article
(This article belongs to the Special Issue Modelling Biological Barriers to Study Molecular Trafficking In Vitro: Advances and Applications)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop