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Bicontinuous Cubic Liquid Crystals as Potential Matrices for Non-Invasive Topical Sampling of Low-Molecular-Weight Biomarkers
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.ORCID iD: 0000-0001-8720-3705
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.ORCID iD: 0000-0001-6254-8539
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.ORCID iD: 0000-0001-5654-4339
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
2023 (English)In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 15, no 8, article id 2031Article in journal (Refereed) Published
Abstract [en]

Many skin disorders, including cancer, have inflammatory components. The non-invasive detection of related biomarkers could therefore be highly valuable for both diagnosis and follow up on the effect of treatment. This study targets the extraction of tryptophan (Trp) and its metabolite kynurenine (Kyn), two compounds associated with several inflammatory skin disorders. We furthermore hypothesize that lipid-based bicontinuous cubic liquid crystals could be efficient extraction matrices. They comprise a large interfacial area separating interconnected polar and apolar domains, allowing them to accommodate solutes with various properties. We concluded, using the extensively studied GMO-water system as test-platform, that the hydrophilic Kyn and Trp favored the cubic phase over water and revealed a preference for locating at the lipid-water interface. The interfacial area per unit volume of the matrix, as well as the incorporation of ionic molecules at the lipid-water interface, can be used to optimize the extraction of solutes with specific physicochemical characteristics. We also observed that the cubic phases formed at rather extreme water activities (>0.9) and that wearing them resulted in efficient hydration and increased permeability of the skin. Evidently, bicontinuous cubic liquid crystals constitute a promising and versatile platform for non-invasive extraction of biomarkers through skin, as well as for transdermal drug delivery.

Place, publisher, year, edition, pages
MDPI, 2023. Vol. 15, no 8, article id 2031
Keywords [en]
tryptophan, kynurenine, tryptophan-to-kynurenine ratio, cancer-related biomarkers, non-invasive extraction, bicontinuous cubic liquid crystal, bilayer partitioning, glycerol monooleate, DOTAP, X-ray diffraction, humidity scanning (HS) QCM-D
National Category
Pharmaceutical Chemistry
Identifiers
URN: urn:nbn:se:mau:diva-62643DOI: 10.3390/pharmaceutics15082031ISI: 001055274500001PubMedID: 37631245Scopus ID: 2-s2.0-85168893889OAI: oai:DiVA.org:mau-62643DiVA, id: diva2:1798020
Available from: 2023-09-18 Created: 2023-09-18 Last updated: 2023-10-19Bibliographically approved
In thesis
1. Biophysical aspects of the skin barrier: towards increased non-invasive extraction and optimized biomarker sampling
Open this publication in new window or tab >>Biophysical aspects of the skin barrier: towards increased non-invasive extraction and optimized biomarker sampling
2021 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The skin provides a link to the body’s health via its rich variety of high and low molecular weight biomarkers, reflecting both systemic diseases (e.g., cancer, diabetes) and local skin disorders (e.g., atopic dermatitis, psoriasis). Non-invasive monitoring of disease-specific biomarkers on the skin surface provides a highly attractive diagnostic procedure as alternative to current practices that normally are biopsy-based and invasive. In order to succeed with non-invasive topical diagnostics, the sampling of biomarkers should proceed in a highly accurate and reproducible manner. Further, a major challenge to achieve this goal is to overcome the outermost skin layer (the stratum corneum, SC) that acts as a remarkable permeability barrier, restricting molecular diffusion in and out of our body, including diffusion of potential biomarkers.

The primary aim of this thesis is to achieve an optimized and reproducible noninvasive sampling of endogenous biomarkers from the skin surface. Here, water plays a crucial role as the hydration degree of the SC has a strong influence on the diffusion of molecules across the skin barrier. In particular, fully hydrated skin is expected to be optimal for increased diffusion of biomarkers in the skin tissue, favoring efficient extraction.

Considering this, to develop a suitable sampling matrix for non-invasive extraction, it is very important to optimize the matrix so that it has a good ability to hydrate the skin as well as a high capacity to absorb the biomarker and finally allow for analytic quantification. The main questions in this thesis are as follows. (i) How long time does it take to reach a stable level of skin hydration? (ii) How do the intrinsic properties of sampling matrices influence the extraction of biomarkers? (iii) What are the effects of the sampling matrices on the biophysical properties of the skin barrier?(iv) Are hydrogels and bicontinuous cubic liquid crystals suitable matrices for noninvasive sampling of endogenous biomarkers? (v) Is reverse iontophoresis a suitable technique to further enhance the extraction endogenous biomarkers?

The hydration of the skin is investigated in vivo and in vitro in order to estimate the time to reach stable hydration level. We show that skin hydration proceeds in two distinct stages with different rates of change of the electrical impedance response and conclude that stable conditions are obtained approximately after 60 min of hydration. We explore the novel approach of using lipid-based bicontinuous cubic liquid crystalline phases as matrices for non-invasive sampling of biomarkers in vivo and invitro and compare them with hydrogel-based materials.

From these investigations, we conclude that both kind of materials show promising capacity of hydrating the skin and collect skin-derived biomarkers. However, the cubic phases are shown to havea bout twice as high extraction capacity, as compared to hydrogels. Further, we show that reverse iontophoresis enhances extraction of a potential cancer biomarker in vitro by at least an order of magnitude, as compared to passive diffusion. Taken together, the results obtained in this thesis can serve as a point-of-departure for future applications based on non-invasive sampling of disease-related biomarkers from skinin clinical diagnostics.

Place, publisher, year, edition, pages
Malmö: Malmö universitet, 2021. p. 70
Series
Malmö University Health and Society Dissertations, ISSN 1653-5383 ; 2021:10
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:mau:diva-48311 (URN)10.24834/isbn.9789178772254 (DOI)9789178772247 (ISBN)9789178772254 (ISBN)
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Note

Paper II published in dissertation as manuscript.

Paper IV published in dissertation as manuscript with title Non-invasive, Topical Sampling of Potential Skin Cancer Biomarkers,Kynurenine and Tryptophan: Study on Healthy Volunteer

Available from: 2021-12-21 Created: 2021-12-21 Last updated: 2023-10-19Bibliographically approved

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Morin, MaximBjörklund, SebastianNilsson, Emelie J.Engblom, Johan

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