Stilbenes in food and medicinal plants have been described as potent antiphlogistic and antioxidant compounds, and therefore, they present an interesting potential for the development of dietary supplements. Among them, macasiamenene F (MF) has recently been shown to be an effective anti-inflammatory and cytoprotective agent that dampens peripheral and CNS inflammation in vitro. Nevertheless, this promising molecule, like other stilbenes and a large percentage of drugs under development, faces poor water solubility, which results in trickier in vivo administration and low bioavailability. With the aim of improving MF solubility and developing a form optimized for in vivo administration, eight types of conventional liposomal nanocarriers and one type of PEGylated liposomes were formulated and characterized. In order to select the appropriate form of MF encapsulation, the safety of MF liposomal formulations was evaluated on THP-1 and THP-1-XBlue-MD2-CD14 monocytes, BV-2 microglia, and primary cortical neurons in culture. Furthermore, the cellular uptake of liposomes and the effect of encapsulation on MF anti-inflammatory effectiveness were evaluated on THP-1-XBlue-MD2-CD14 monocytes and BV-2 microglia. MF (5 mol %) encapsulated in PEGylated liposomes with an average size of 160 nm and polydispersity index of 0.122 was stable, safe, and the most promising form of MF encapsulation keeping its cytoprotective and anti-inflammatory properties.

Chulabhorn Research Institute Kamphaeng Phet 6 Road Laksi TH 10210 Bangkok Thailand

Department of Molecular Pharmacy Faculty of Pharmacy Masaryk University Palackého tř 1946 1 CZ 612 00 Brno Czech Republic

Department of Natural Drugs Faculty of Pharmacy Masaryk University Palackého tř 1946 1 CZ 612 00 Brno Czech Republic

Department of Pharmacology and Toxicology Veterinary Research Institute Hudcova 296 70 CZ 621 00 Brno Czech Republic

Department of Pharmacology Faculty of Medicine Masaryk University Kamenice 753 5 CZ 625 00 Brno Czech Republic

IPMC UMR 7275 Université Côte d'Azur CNRS 660 Route des Lucioles Sophia Antipolis F 06560 Valbonne France

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