title: Modulatory effect of human plasma on the internal nanostructure and size characteristics of liquid-crystalline nanocarriers.
abstract: The inverted-type liquid-crystalline dispersions comprising cubosomes and hexosomes hold much potential for drug solubilization and site-specific targeting on intravenous administration. Limited information, however, is available on the influence of plasma components on nanostructural and morphological features of cubosome and hexosome dispersions, which may modulate their stability in the blood and their overall biological performance. Through an integrated approach involving SAXS, cryo-TEM, and nanoparticle tracking analysis (NTA) we have studied the time-dependent effect of human plasma (and the plasma complement system) on the integrity of the internal nanostructure, morphology, and fluctuation in size distribution of phytantriol (PHYT)-based nonlamellar crystalline dispersions. The results indicate that in the presence of plasma the internal nanostructure undergoes a transition from the biphasic phase (a bicontinuous cubic phase with symmetry Pn3m coexisting with an inverted-type hexagonal (H2) phase) to a neat hexagonal (H2) phase, which decreases the median particle size. These observations were independent of a direct effect by serum albumin and dispersion-mediated complement activation. The implication of these observations in relation to soft nanocarrier design for intravenous drug delivery is discussed.
authors.forename: Intan Diana Mat
authors.initials: ID
authors.lastname: Azmi
authors.forename: Linping
authors.initials: L
authors.lastname: Wu
authors.forename: Peter Popp
authors.initials: PP
authors.lastname: Wibroe
authors.forename: Christa
authors.initials: C
authors.lastname: Nilsson
authors.forename: Jesper
authors.initials: J
authors.lastname: Østergaard
authors.forename: Stefan
authors.initials: S
authors.lastname: Stürup
authors.forename: Bente
authors.initials: B
authors.lastname: Gammelgaard
authors.affiliation: §Centre for Drug Research, University of Helsinki, FIN-00014 Helsinki, Finland.|∥School of Pharmacy, University of Eastern Finland, FIN-70211 Kuopio, Finland.
authors.forename: Arto
authors.initials: A
authors.lastname: Urtti
authors.forename: Seyed Moein
authors.initials: SM
authors.lastname: Moghimi
authors.forename: Anan
authors.initials: A
authors.lastname: Yaghmur
mesh_terms: D020285:Cryoelectron Microscopy; D004337:Drug Carriers / Q000737:chemistry; D005233:Fatty Alcohols / Q000737:chemistry; D006801:Humans; D050866:Liquid Crystals / Q000737:chemistry* / Q000648:ultrastructure; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D004337:Drug Carriers; D005233:Fatty Alcohols; C508873:3,7,11,15-tetramethyl-1,2,3-hexadecanetriol