Reversible Masking Using Low-Molecular-Weight Neutral Lipids to Achieve Optimal-Targeted Delivery

Figure 2

Proposed model showing cross-sections of extruded DOTAP: Chol liposomes (BIVs) interacting with nucleic acids. Nucleic acids adsorb onto a BIV via electrostatic interactions. Attraction of a second BIV to this complex results in further charge neutralization. Expanding electrostatic interactions with nucleic acids causes inversion of the larger BIV and total encapsulation of the nucleic acids. Inversion can occur in these liposomes because of their excess surface area, which allows them to accommodate the stress created by the nucleic acid-lipid interactions. Nucleic acid binding reduces the surface area of the outer leaflet of the bilayer and induces the negative curvature due to lipid ordering and reduction of charge repulsion between cationic lipid headgroups. Condensation of the internalized nucleic acid-lipid sandwich expands the space between the bilayers and may induce membrane fusion to generate the apparently closed structures. The enlarged area shows the arrangement of nucleic acids condensed between two 4 nm bilayers of extruded DOTAP:Chol.