Novel controlled-release polylactic-co-glycolic acid (PLGA) nanoparticles for sodium thiosulphate, a hydrogen sulphide donor, retains pro-angiogenic potential of hydrogen sulphide

Abstract

Hydrogen sulphide (H2S) is an endogenous gaseous signalling molecule observing cardioprotective qualities in various experimental models. However, its therapeutic application is limited due to rapid release in vivo and potential toxicity. Controlled-release nanoparticles (NPs), such as polylactic-co-glycolic acid (PLGA) NPs entrapping H2S compounds may address these issues. PLGA NPs’ encapsulating sodium thiosulphate (STS), a H2S donor, were prepared by emulsification and sonication-solvent evaporation in polyvinyl alcohol (PVA). Sonication time was varied between 15 and 45 s and PVA concentration varied between 0.3 and 0.7% w/v. NPs were characterised, cellular uptake, H2S generation and encapsulated STS angiogenic potential was explored. An increase in sonication time as well as PVA concentration decreased NPs size resulting in an increase in STS release kinetics and cellular uptake over 24 h. Encapsulated STS gave a controlled release of H2S over 24 h whereas non-encapsulated STS peaked at 2 h. Finally, we observed entrapped STS maintained pro-angiogenic potential. PLGA NPs are a promising controlled-release delivery system with potential to offer sustained H2S levels. Results of this study demonstrate formulation of STS-loaded PLGA NPs provides a controlled-release of STS and therefore H2S. NPs are internalised into cells and critically, PLGA NPs are able to maintain the pro-angiogenic potential of H2S.