Hemocompatible and immune-safe library of citrem-phospholipid liquid crystalline nanoplatforms.

Liposomes have been used as efficient drug carriers for more than several decades. Recently, lyotropic non-lamellar liquid crystalline (LC) nanodispersions consisting of internally self-assembled nanoparticles (e.g., cubosomes and hexosomes) have received attention as an alternative platform for drug delivery, imaging, and design of diagnostic modalities [1]. In particular, they are attractive for development of injectable carriers for accommodating poorly water soluble drugs, hydrophilic peptides, and diagnostic agents. Some LC nanodispersions, however, are known to have poor hemocompatibility including hemolysis and complement activation [2], and potential toxicity of certain lipid/amphiphile constituents [1,2]. This limits their use as drug delivery vehicles for intravenous (I.V.) administration. The development of non-lamellar LC aqueous nanodispersions as safe and efficient I.V. drug carriers requires amechanistic and interdisciplinary approach focusing on the formation of nanoparticles composed of naturally occurring lipids that are structurally stable in human plasma, fully hemocompatible, and capable of solubilizing various drugs. Accordingly, the use of a naturally occurring biodegradable lipid such as phosphatidylcholine (PC) remains a viable option as a promising safer amphiphile. Overcoming the strong tendency of PC to form lamellar phases, however, is challenging and requires the addition of other biologically relevant lipids or an apolar non-toxic solvent modifier [3]. A paper in this Issue by complimentary research teams of Dr. Yaghmur and Professor Moghimi [4] addresses the raised concepts and limitations in the LC field. They introduce a versatile library of self-assembled lamellar and non-lamellar LC nanoparticles composed from two biologically compatible components: soy phosphatidylcholine and citrem. Citrem is an anionic citric acid ester of monoglycerides, and it has been approved by the United States Food and Drug Administration as an emulsifying agent in food products. It also has anti-oxidative properties. The nanoparticles’ self-assembled interior is sensitive to lipid composition and increasing the citrem concentration induces the formation of lamellar/nonlamellar LC and micellar nano-assemblies. The structural diversity was spanned into four distinct phases: Lα, V2, H2, and L2 leading to colloidal transformation from vesicles via cubosomes and hexosomes to an emulsified L2 phase (ELP), respectively. Themorphological and structural features of the citrem-phospholipid library were thoroughly characterized through an integrated approach involving synchrotron small-angle X-ray scattering (SAXS), cryogenic transmission electron microscopy (cryo-TEM), and nanoparticle tracking analysis (NTA). There are five unique features with this initiative. First, this strategy has overcome the need for a secondary emulsifier, which is necessary to achieve colloidal stability for non-lamellar LC aqueous dispersions. Second, thedescribedbinary systemcould also beproducedwith low energy input, andwithout the use of an organic hydrotropic solvent. This is highly advantageous for encapsulation of temperature-sensitive and/or