Citrem modulates internal nanostructure of glyceryl monooleate dispersions and bypasses complement activation: Towards development of safe tunable intravenous lipid nanocarriers.

Lyotropic non-lamellar liquid crystalline (LLC) aqueous nanodispersions hold a great promise in drug solubilization and delivery, but these nanosystems often induce severe hemolysis and complement activation, which limit their applications for safe intravenous administration. Here, we engineer and characterize LLC aqueous nanodispersions from a binary lipid mixture consisting of 2,3-dihydroxypropyl oleate (glyceryl monooleate) and medium-chain triglycerides with tunable internal nanostructures and improved hemocompatibility controlled by citrem as stabilizer. Citrem, in a concentration-dependent manner, modulates the internal nanostructure of LLC dispersions from a biphasic H2/L2 feature to a neat L2 phase, where the latter resembles "thread-like" swollen micelles. Citrem stabilization totally overcomes hemolysis and complement activation, thus realizing the potential of the engineered LLC aqueous nanodispersions for exploitation in intravenous delivery of drugs and contrast agents. FROM THE CLINICAL EDITOR: The complement system often gets activated after intravenous injection of nano drug-carriers. This may result in detrimental systemic effects. The authors described in this article the use of citrem as a stabilizing agent and showed the ability of this agent to abolish complement activation. Hence, citrem may prove to be an important component of tunable LLC nanocarriers that may be useful in future clinical setting.