Transdermal Delivery of a Hydrogen Sulphide Donor, ADT-OH Using Aqueous Gel Formulations for the Treatment of Impaired Vascular Function:an Ex Vivo Study

Abstract

Purpose Hydrogen sulphide (H2S) is an important signalling molecule involved in the regulation of several physiological and pathophysiological processes. The objective of this study was to investigate the feasibility of transdermal delivery of ADT-OH, a H2S donor, by investigating the transdermal flux of aqueous gels loaded with penetration enhancers or liposomes. Furthermore, we explored the ability of permeated ADT-OH to promote angiogenesis and mitochondrial bioenergetics in HUVEC cells. Methods Aqueous hypromellose gels (5% w/v) were prepared with up to 10% v/v propylene glycol (PG) or deformable liposomes with 0.025% w/w ADT-OH. ADT-OH permeation from formulations across excised murine skin into PBS was quantified over 24 h using HPLC-UV detection. Media was collected and applied to HUVEC cells to evidence ADT-OH functionality following permeation. Tube formation assays were performed as indicative of angiogenesis and mitochondrial oxygen consumption was evaluated using a Seahorse XF24. Results Increasing the loading of PG caused an increase in ADT-OH permeation rate across skin and a decrease in dermal drug retention whereas liposomal gels produced a slow-release profile. Treatment of HUVEC’s using conditioned media collected from the ADT-OH loaded permeation studies enhanced tube formation and the basal oxygen consumption rates after 30 min of treatment. Conclusions These findings demonstrate that transdermal delivery of ADT-OH may provide a promising approach in the treatment of impaired vascular function. Gels prepared with 10% v/v PG have the potential for use in conditions requiring rapid H2S release whereas liposomal loaded gels for treatment requiring sustained H2S release.

Publication DOI: https://doi.org/10.1007/s11095-021-03164-z
Divisions: College of Health & Life Sciences > Aston Medical School > Translational Medicine Research Group (TMRG)
College of Health & Life Sciences > Aston Medical School
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
College of Health & Life Sciences > School of Optometry > Optometry
College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Uncontrolled Keywords: controlled release,hydrogen sulphide donors,release kinetics,skin penetration enhancer,transdermal drug delivery,Biotechnology,Molecular Medicine,Pharmacology,Pharmaceutical Science,Organic Chemistry,Pharmacology (medical)
Publication ISSN: 1573-904X
Full Text Link:
Related URLs: https://link.sp ... 095-021-03164-z (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2022-02
Published Online Date: 2022-01-27
Accepted Date: 2022-01-21
Authors: Marwah, Mandeep (ORCID Profile 0000-0003-4881-003X)
Shokr, Hala
Sanchez Aranguren, Lissette (ORCID Profile 0000-0002-4663-5752)
Badhan, Raj K.S. (ORCID Profile 0000-0002-0904-9324)
Wang, Keqing (ORCID Profile 0000-0001-6239-6344)
Ahmad, Shakil (ORCID Profile 0000-0002-9294-0475)

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