Liposomes - bio-inspired nano-containers for physically triggered targeted drug delivery

For natural scientists and engineers, learning from nature has tradition and is often driven by bio-inspired processes and materials. For example, engineers have designed multifunctional materials with hierarchical structures. Lipid bilayers, the principal components of cell membranes, can form vesicles, termed liposomes. Such liposomes are usually recognized as foreign by the immune system of a patient, which makes it challenging to use liposomes as containers for targeted drug delivery. There are, however, promising non-spherical, mechano-sensitive, artificial liposomes about 100 nm in diameter, which were recently identified. These bio-inspired containers offer a wide range of applications. In particular, the targeted release at critically stenosed arteries formed as a result of atherosclerosis significantly reduces the undesired side effects such as a drop of blood pressure. It is well known that FDA-approved liposomal drugs, currently on the market, often induce adverse immune responses. Therefore, to exclude the hypersensitivity of the recently discovered mechano-sensitive liposomes, we have performed in vitro complement activation experiments and related animal studies with pigs. Recently, it has been shown that the drug-free Pad-PC-Pad liposomes surprisingly lack any complement activation. In this study, we demonstrate that nitroglycerin-loaded liposomes with relevant human therapeutic dosage exhibit low complement activation compared to the FDA-approved phospholipid drugs, including Abelcet. Furthermore, the liposomal suspensions applied are stable for a period of more than two months. Consequently, the non-spherical liposomes of nanometer size we have developed are promising containers for physically triggered, targeted drug delivery.