Manganese in Diagnostics: A Preformulatory Study.

Maddalena Sguizzato,Lorenza Marvelli,Markus Drechsler,Walter Pula,Antonella Pagnoni,Anna Bordin,Rita Cortesi

doi:10.3390/pharmaceutics14010108

Maddalena Sguizzato, Lorenza Marvelli + Show 5 more

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https://doi.org/10.3390/pharmaceutics14010108

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Abstract

This investigation aims to find lipid-based nanosystems to be used as tools to deliver manganese for diagnostic purposes in multimodal imaging techniques. In particular, the study describes the production and characterization of aqueous dispersions of anionic liposomes as delivery systems for two model manganese-based compounds, namely manganese chloride and manganese acetylacetonate. Negatively charged liposomes were obtained using four different anionic surfactants, namely sodium docusate (SD), N-lauroylsarcosine (NLS), Protelan AG8 (PAG) and sodium lauroyl lactylate (SLL). Liposomes were produced by the direct hydration method followed by extrusion and characterized in terms of size, polydispersity, surface charge and stability over time. After extrusion, liposomes are homogeneous and monodispersed with an average diameter not exceeding 200 nm and a negative surface charge as confirmed by ζ potential measurement. Moreover, as indicated by atomic absorption spectroscopy analyses, the loading of manganese-based compounds was almost quantitative. Liposomes containing NLS or SLL were the most stable over time and the presence of manganese-based compounds did not affect their size distribution. Liposomes containing PAG and SD were instable and therefore discarded. The in vitro cytotoxicity of the selected anionic liposomes was evaluated by MTT assay on human keratinocyte. The obtained results highlighted that the toxicity of the formulations is dose dependent.

Highlights

Diagnostic imaging research has led to the development of multimodal imaging techniques such as positron emission tomography (PET)/magnetic resonance imaging (MRI), which allows for metabolic information provided by PET and morphological information provided by MRI to be obtained at the same time [1,2,3]
The attention was focused on the development of anionic liposomal systems able to carry the manganese ion (i.e., Mn2+ or Mn3+), characterized by high toxicity, with the aim to avoid its release into biological fluids before reaching the site of interest
Systems able to carry the manganese ion (i.e., Mn or Mn ), characterized by high lipid bilayer theaim liposomes: hydrophilic heads are fluids arranged in such a way assite to be toxicity, withofthe to avoid the its release into biological before reaching the of in contact with the aqueous medium, while the lipophilic tails remain in close proximity interest [38,39]

Summary

Introduction

Diagnostic imaging research has led to the development of multimodal imaging techniques such as positron emission tomography (PET)/magnetic resonance imaging (MRI), which allows for metabolic information provided by PET and morphological information provided by MRI to be obtained at the same time [1,2,3]. The optimization of this technique has highlighted the need to design and develop specific contrast agents capable of carrying out this double and simultaneous detection [4]. A fundamental prerequisite for achieving integration between the two mentioned imaging modalities is the use of a chemically identical radioactive and paramagnetic contrast agent. In this regard, manganese (Mn) appears to be the ideal candidate as a potential bimodal contrast agent [5]. Its oxidation state ranges from −3 to +7, but the most common forms found in living tissues are Mn2+ and Mn3+ [6], which, being endowed with paramagnetic properties, allow their

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