title: A structurally diverse library of safe-by-design citrem-phospholipid lamellar and non-lamellar liquid crystalline nano-assemblies.
abstract: Non-lamellar liquid crystalline aqueous nanodispersions, known also as ISAsomes (internally self-assembled 'somes' or nanoparticles), are gaining increasing interest in drug solubilisation and bio-imaging, but they often exhibit poor hemocompatibility and induce cytotoxicity. This limits their applications in intravenous drug delivery and targeting. Using a binary mixture of citrem and soy phosphatidylcholine (SPC) at different weight ratios, we describe a library of colloidally stable aqueous and hemocompatible nanodispersions of diverse nanoarchitectures (internal self-assembled nanostructures). This engineered library is structurally stable in human plasma as well as being hemocompatible (non-hemolytic, and poor activator of the complement system). By varying citrem to lipid weight ratio, the nanodispersion susceptibility to macrophage uptake could also be modulated. Finally, the formation of nanodispersions comprising internally V2 (inverse bicontinuous cubic) and H2 (inverse hexagonal) nanoarchitectures was achieved without the use of an organic solvent, a secondary emulsifier, or high-energy input. The tunable binary citrem/SPC nanoplatform holds promise for future development of hemocompatible and immune-safe nanopharmaceuticals.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark; Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400, UPM, Serdang, Selangor Darul Ehsan, Malaysia.
authors.forename: Intan D M
authors.initials: ID
authors.lastname: Azmi
authors.affiliation: Nanomedicine Laboratory, Centre for Pharmaceutical Nanotechnology and Nanotoxicology, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Wibroe
authors.affiliation: Nanomedicine Laboratory, Centre for Pharmaceutical Nanotechnology and Nanotoxicology, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Lin-Ping
authors.initials: LP
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Ali I
authors.initials: AI
authors.lastname: Kazem
authors.affiliation: Elettra-Sincrotrone Trieste, Strada Statale 14, 34149 Basovizza, Trieste, Italy.
authors.forename: Heinz
authors.initials: H
authors.lastname: Amenitsch
authors.affiliation: Nanomedicine Laboratory, Centre for Pharmaceutical Nanotechnology and Nanotoxicology, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark; NanoScience Centre, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen Ø, Denmark; School of Medicine, Pharmacy and Health, Durham University, Queen's Campus, Stockton-on-Tees TS17 6BH, UK. Electronic address: moein.moghimi@gmail.com.
authors.forename: Seyed M
authors.initials: SM
authors.lastname: Moghimi
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark. Electronic address: anan.yaghmur@sund.ku.dk.
authors.forename: Anan
authors.initials: A
authors.lastname: Yaghmur
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D050866:Liquid Crystals / Q000737:chemistry*; D051379:Mice; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D000067996:RAW 264.7 Cells
chemical_list: D004337:Drug Carriers; D010743:Phospholipids
keywords: Complement system; Cubosomes; Hexosomes; Immune-safe nanopharmaceuticals; Lamellar and non-lamellar liquid crystalline phases; Macrophage