title: Investigation of the interaction between modified ISCOMs and stratum corneum lipid model systems.
abstract: The modified ISCOMs, so-called Posintro nanoparticles, provide an opportunity for altering the surface charge of the particles, which influences their affinity for the negatively charged antigen sites, cell membranes and lipids in the skin. Hypothetically, this increases the passage of the ISCOMs (or their components) and their load through the stratum corneum. The subsequent increase in the uptake by the antigen-presenting cells results in enhanced transcutaneous immunization. To understand the nature of penetration of Posintro nanoparticles into the intercorneocyte space of the stratum corneum, the interaction between the nanoparticles and lipid model systems in form of liposomes and/or supported lipid bilayer was studied. As a lipid model we used Stratum Corneum Lipid (SCL), a mixture similar in composition to the lipids of the intercorneocyte space. By Förster Resonance Energy Transfer (FRET), Atomic Force Microscopy (AFM), Electrochemical Impedance Spectroscopy (EIS) and cryo-Transmission Electron Microscopy (cryo-TEM) it was shown that application of nanoparticles to the SCL bilayers results in lipid disturbance. Investigation of this interaction by means of Isothermal Titration Calorimetry (ITC) confirmed existence of an enthalpically unfavorable reaction. All these methods demonstrated that the strength of electrostatic repulsion between the negatively charged SCL and the nanoparticles affected their interaction, as decreasing the negative charge of the Posintro nanoparticles leads to enhanced disruption of lipid organization.
authors.affiliation: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Henriette Baun
authors.initials: HB
authors.lastname: Madsen
authors.forename: Helle M
authors.initials: HM
authors.lastname: Arboe-Andersen
authors.forename: Noemi
authors.initials: N
authors.lastname: Rozlosnik
authors.forename: Flemming
authors.initials: F
authors.lastname: Madsen
authors.forename: Peter
authors.initials: P
authors.lastname: Ifversen
authors.forename: Marina R
authors.initials: MR
authors.lastname: Kasimova
authors.forename: Hanne Mørck
authors.initials: HM
authors.lastname: Nielsen
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D017097:Electric Impedance; D004563:Electrochemistry; D031541:Fluorescence Resonance Energy Transfer; D016882:ISCOMs / Q000494:pharmacology*; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D018625:Microscopy, Atomic Force; D053758:Nanoparticles; D012867:Skin / Q000737:chemistry*; D012869:Skin Absorption; D013816:Thermodynamics
chemical_list: D000276:Adjuvants, Immunologic; D016882:ISCOMs; D008055:Lipids; D008081:Liposomes