Sydnone, imidazolium salt and their gold(I) complex loaded in oil-in-water microemulsions: Physicochemical characterization and in vivo toxicity toward biological applications

Abstract

Gold complexes containing sydnone ligands have attracted increasing interest in medicinal chemistry; however, their limited stability in biological environments and the scarce information on their toxicity hinder further application. Encapsulation in nanostructured liquid systems offers a promising strategy to enhance stability and prevent degradation. In this work, oil-in-water microemulsions were developed as nanostructured carriers for a 3-mesityl sydnone, an imidazolium salt, their combined system, and a gold (I) N-heterocyclic carbene complex. Formulations based on oleic acid, decaethylene glycol mono-dodecyl ether, and ethanol were prepared by titration, yielding transparent, isotropic, and physically stable systems. Dynamic light scattering showed droplet sizes below 200 nm with low polydispersity, while conductivity measurements confirmed the formation of oil-in- water microemulsions. No phase separation was observed after heating–cooling cycles. Photodegradation studies under UVA and UVB irradiation revealed a slight improvement in the photostability of the encapsulated complex. In-vivo toxicity was assessed in zebrafish (Danio rerio) as a preliminary evaluation of the biological effects of the formulations. Additionally, antioxidant activity, evaluated by the DPPH assay, showed moderate radical scavenging capacity (SC₅₀ = 114.5 μg mL-1). Overall, these results highlight the potential of microemulsions as nanostructured liquid carriers for stabilizing sydnone-based compounds and gold complexes, providing a basis for further studies aimed at evaluating their stability and biological behavior under more controlled conditions.