Cochleates bridged by drug molecules

Abstract

A new type of cochleate, able to microencapsulate water-soluble cationic drugs or peptides into its inter-lipid bi-layer space, was formed through interaction between negatively charged lipids and drugs or peptides acting as the inter-bi-layer bridges instead of multi-cationic metal ions. This new type of cochleate opened up to form large liposomes when treated with EDTA, suggesting that cationic organic molecules can be extracted from these cochleates in a way similar to multivalent metal ions from metal ion-bridged cochleates. Cochleates can be produced in sub-micron size using a method known as “hydrogel isolated cochleation” or simply by increasing the ratio of multivalent cationic peptides over negatively charged liposomes. When nanometer-sized cochleates and liposomes containing the same fluorescent labeled lipid component were incubated with human fibroblasts cells under identical conditions, cells exposed to cochleates showed bright fluorescent cell surfaces, whereas those incubated with liposomes did not. This result suggests that cochleates’ edges made them fuse with the cell surfaces as compared to edge free liposomes. This mechanism of cochleates’ fusion with cell membrane was supported by a bactericidal activity assay using tobramycin cochleates, which act by inhibiting intracellular ribosomes. Tobramycin bridged cochleates in nanometer size showed improved antibacterial activity than the drug's solution.