Antitubercular drug-loaded multi-liposomes vectors as innovative combinatorial therapy for pulmonary tuberculosis

Funding Body: Phospholipid Research Center, Heidelberg
Simona Sennato
In this project we will develop a new liposome-based multi-drug delivery system loading simultaneously two anti Mycobacterium tuberculosis-drugs, formed by different liposomes glued together in “multi-compartment” clusters. The innovation is connected both with the modular structure of the carrier and with the possibility to transport and deliver different drugs simultaneously towards the same target, encapsulating them in the different liposomes forming the aggregates. It is recognized that inhalation of drug-loaded liposomes offers a potential value in antituberculosis-therapy. Multicompartment liposomal clusters, with size larger than a single vesicles, have been demonstrated to possess an intrinsic selectivity towards macrophages, thus representing an emerging platform for the intracellular delivery of antitubercolar drugs to the primary site of infection. The opportunity of combining an increased efficacy of intracellular delivery with the ability of carrying several different active molecules, simultaneously and with a controlled stoichiometry, to the same target could represent a significant breakthrough. Nowadays, the increasing spread of biocompatible liposome-based drug nanocarriers is a result of the unique properties of lipids and of the vesicular structure. Here we will tackle advantage of the large variety of phospholipids to optimize the formulation of liposomes in terms of physico-chemical properties of the lipid bilayer, stability of the vesicles and drug encapsulation efficiency, with the aim to improve their biocompatibility and ability to entrap drugs, optimizing also their pharmacokinetics and therapeutic index