At present, conventional microdialysis (MD) techniques cannot efficiently sample lipids in vivo, possibly due to the high mass transfer resistance and/or the serious adsorption of lipids onto the semi-permeable membrane of a MD probe. The in vivo monitoring of lipids could be of great significance for the study of disease development and mechanisms. In this work, an open-flow microperfusion (OFM) probe was fabricated, and the conditions for sampling lipids via OFM were optimized. Using OFM, the recovery of lipid standards was improved to more than 34.7%. OFM is used for the in vivo sampling of lipids in mouse liver tissue with fibrosis, and it is then combined with mass spectrometry (MS) to perform lipidomic analysis. 156 kinds of lipids were identified in the dialysate collected via OFM, and it was found that the phospholipid levels, including PC, PE, and SM, were significantly higher in a liver suffering from fibrosis. For the first time, OFM combined with MS to sample and analyze lipids has provided a promising platform for in vivo lipidomic studies.
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http://dx.doi.org/10.1039/d0an02189j | DOI Listing |
Despite the prevalence and the impact on quality of life of dermatological indications, drug products to treat such conditions have rarely been blockbusters. The prevailing perception of a limited commercial potential of dermatological drug products has restricted innovation and encouraged a more conservative development approach. For example, the focus was on repurposing/reformulation of existing active pharmaceutical ingredients (APIs) specifically for the topical delivery route.
View Article and Find Full Text PDFAnalyst
September 2024
Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry Chinese Academy of Sciences, Beijing Mass Spectrum Center, Beijing 100190, China.
Correction for 'Open-flow microperfusion combined with mass spectrometry for liver lipidomic analysis' by Tuo Li , , 2021, , 1915-1923, https://doi.org/10.1039/D0AN02189J.
View Article and Find Full Text PDFJ Proteome Res
August 2024
HEALTH - Institute for Biomedical Research and Technologies, Joanneum Research Forschungsgesellschaft mbH, Neue Stiftingtalstraße 2, Graz 8010, Austria.
Dupilumab is a monoclonal antibody approved for the treatment of atopic dermatitis (AD); however, its effects on molecular, cellular, and immunological levels remain to be elucidated. In this study, blood and dermal interstitial fluid (ISF) from nonlesional (NL) and lesional (L) skin were collected from eight patients with moderate to severe AD, before (visit 2-v2) and at the end of a 16-week treatment with dupilumab (visit 10-v10). Clinical treatment effect was demonstrated by significantly decreased AD severity scores at the end of treatment.
View Article and Find Full Text PDFEur J Pharm Sci
September 2024
Institute for Biomedical Research and Technologies (HEALTH), Joanneum Research Forschungsgesellschaft m.b.H, Neue Stiftingtalstrasse 2, 8010, Graz, Austria; Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
Background: Using accurate, sensitive, reproducible and efficient in vivo cutaneous pharmacokinetics (PK)-based bioequivalence (BE) approaches can promote the development of topical generic drug products. A clinical dermal open flow microperfusion (dOFM) study has previously demonstrated the BE of topical drug products containing a hydrophilic drug. However, the utility of dOFM to evaluate the topical BE of drug products containing moderately lipophilic drugs, more representative of most topical drugs, has not yet been established.
View Article and Find Full Text PDFAAPS PharmSciTech
February 2024
Simulations Plus, Incorporated, 42505 10th Street West, Lancaster, California, 93534, USA.
Quantitative in silico tools may be leveraged to mechanistically predict the dermato-pharmacokinetics of compounds delivered from topical and transdermal formulations by integrating systems of rate equations that describe permeation through the formulation and layers of skin and pilo-sebaceous unit, and exchange with systemic circulation via local blood flow. Delivery of clobetasol-17 propionate (CP) from Dermovate cream was simulated using the Transdermal Compartmental Absorption & Transit (TCAT) Model in GastroPlus. The cream was treated as an oil-in-water emulsion, with model input parameters estimated from publicly available information and quantitative structure-permeation relationships.
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