In recent years, polymerization-induced self-assembly (PISA) has emerged as a powerful method for the straightforward synthesis of polymer nanoparticles at high concentration. In this study, we describe for the first time the synthesis of poly(2-oxazoline) nanoparticles by dispersion cationic ring-opening polymerization-induced self-assembly (CROPISA) in n-dodecane. Specifically, a n-dodecane-soluble aliphatic poly(2-(3-ethylheptyl)-2-oxazoline) (PEHOx) block was chain-extended with poly(2-phenyl-2-oxazoline) (PPhOx). While the PhOx monomer is soluble in n-dodecane, its polymerization leads to n-dodecane-insoluble PPhOx, which leads to in situ self-assembly of the formed PEHOx-b-PPhOx copolymers. The polymerization kinetics and micellization upon second block formation were studied, and diverse nanoparticle dispersions were prepared, featuring varying block lengths and polymer concentrations, leading to dispersions with distinctive morphologies and physical properties. Finally, we developed a single-step protocol for the synthesis of polymer nanoparticles directly from monomers via gradient copolymerization CROPISA, which exploits the significantly greater reactivity of EHOx compared to that of PhOx during the statistical copolymerization of both monomers. Notably, this approach provides access to formulations with monomer compositions otherwise unattainable through the block copolymerization method. Given the synthetic versatility and application potential of poly(2-oxazolines), the developed CROPISA method can pave the way for advanced nanomaterials with favorable properties as demonstrated by using the obtained nanoparticles for stabilization of Pickering emulsions.

• Keywords
• CROP, Copolymerization, Nanoparticles, PISA, Poly(2-oxazoline)s,
• Publication type
• Journal Article MeSH

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.

• Publication type
• Journal Article MeSH