Sodium Thiosulphate-Loaded Liposomes Control Hydrogen Sulphide Release and Retain Its Biological Properties in Hypoxia-like Environment


Hypoxia, or insufficient oxygen availability is a common feature in the development of a myriad of cardiovascular-related conditions including ischemic disease. Hydrogen sulphide (H2S) donors, such as sodium thiosulphate (STS), are known for their cardioprotective properties. However, H2S due to its gaseous nature, is released and cleared rapidly, limiting its potential translation to clinical settings. For the first time, we developed and characterised liposome formulations encapsulating STS and explored their potential for modulating STS uptake, H2S release and the ability to retain pro-angiogenic and biological signals in a hypoxia-like environment mirroring oxygen insufficiency in vitro. Liposomes were prepared by varying lipid ratios and characterised for size, polydispersity and charge. STS liposomal encapsulation was confirmed by HPLC-UV detection and STS uptake and H2S release was assessed in vitro. To mimic hypoxia, cobalt chloride (CoCl2) was administered in conjunction with formulated and non-formulated STS, to explore pro-angiogenic and metabolic signals. Optimised liposomal formulation observed a liposome diameter of 146.42 ± 7.34 nm, a polydispersity of 0.22 ± 0.19, and charge of 3.02 ± 1.44 mV, resulting in 25% STS encapsulation. Maximum STS uptake (76.96 ± 3.08%) from liposome encapsulated STS was determined at 24 h. Co-exposure with CoCl2 and liposome encapsulated STS resulted in increased vascular endothelial growth factor mRNA as well as protein expression, enhanced wound closure and increased capillary-like formation. Finally, liposomal STS reversed metabolic switch induced by hypoxia by enhancing mitochondrial bioenergetics. These novel findings provide evidence of a feasible controlled-delivery system for STS, thus H2S, using liposome-based nanoparticles. Likewise, data suggests that in scenarios of hypoxia, liposomal STS is a good therapeutic candidate to sustain pro-angiogenic signals and retain metabolic functions that might be impaired by limited oxygen and nutrient availability.

Publication DOI:
Divisions: College of Health & Life Sciences > Aston Medical School > Translational Medicine Research Group (TMRG)
College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > School of Optometry > Optometry
College of Health & Life Sciences > Aston Medical School
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// 4.0/). Funding Information: This research was funded the Royal Society Grant-Round 1 2021 (RGS\R1\221169) awarded to LSA. Additionally, this study was partially funded by the Joint Research Group Fund 2020–2021 Internal grant awarded to LSA and MKM from the College of Health and Life Sciences, Aston University, Birmingham, UK.
Uncontrolled Keywords: Article,liposomes,controlled-release,drug delivery systems,hydrogen sulphide,angiogenesis,mitochondrial metabolism
Publication ISSN: 2076-3921
Last Modified: 03 Apr 2024 07:34
Date Deposited: 07 Nov 2022 15:32
Full Text Link:
Related URLs: https://www.mdp ... 3921/11/11/2092 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2022-11
Published Online Date: 2022-10-24
Accepted Date: 2022-10-18
Submitted Date: 2022-09-08
Authors: Sanchez-Aranguren, Lissette (ORCID Profile 0000-0002-4663-5752)
Grubliauskiene, Milda
Shokr, Hala
Balakrishnan, Pavanjeeth
Wang, Keqing (ORCID Profile 0000-0001-6239-6344)
Ahmad, Shakil (ORCID Profile 0000-0002-9294-0475)
Marwah, Mandeep Kaur (ORCID Profile 0000-0003-4881-003X)



Version: Published Version

License: Creative Commons Attribution

| Preview

Export / Share Citation


Additional statistics for this record