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

Lissette Sanchez-Aranguren*, Milda Grubliauskiene, Hala Shokr, Pavanjeeth Balakrishnan, Keqing Wang, Shakil Ahmad, Mandeep Kaur Marwah*, Eizo Marutani (Editor)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Article number2092
Number of pages20
Issue number11
Early online date24 Oct 2022
Publication statusPublished - Nov 2022

Bibliographical note

© 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.


  • Article
  • liposomes
  • controlled-release
  • drug delivery systems
  • hydrogen sulphide
  • angiogenesis
  • mitochondrial metabolism


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