TY - JOUR

T1 - Investigation of the interaction between modified ISCOMs and stratum corneum lipid model systems

AU - Madsen, Henriette Baun

AU - Arboe-Andersen, Helle M

AU - Rozlosnik, Noemi

AU - Madsen, Flemming

AU - Ifversen, Peter

AU - Kasimova, Marina R

AU - Nielsen, Hanne Mørck

N1 - 2010. Published by Elsevier B.V.

PY - 2010/9

Y1 - 2010/9

N2 - 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.

AB - 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.

KW - Adjuvants, Immunologic

KW - Electric Impedance

KW - Electrochemistry

KW - Fluorescence Resonance Energy Transfer

KW - ISCOMs

KW - Lipids

KW - Liposomes

KW - Microscopy, Atomic Force

KW - Nanoparticles

KW - Skin

KW - Skin Absorption

KW - Thermodynamics

U2 - 10.1016/j.bbamem.2010.06.006

DO - 10.1016/j.bbamem.2010.06.006

M3 - Journal article

C2 - 20542013

VL - 1798

SP - 1779

EP - 1789

JO - B B A - General Subjects

JF - B B A - General Subjects

SN - 0304-4165

IS - 9

ER -