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

People involved

Dr. Simona Sennato (Postdoc fellow sponsored by the PRC) – CNR-ISC, UOS University of Rome “La Sapienza”, Rome, Italy (simona.sennato@cnr.it, simona.sennato@roma1.infn.it)

Assoc.Prof. Dr. Maria Carafa (Main partner) – Chemistry and Drug Technology Department, La Sapienza

Abstract

In this project, a new liposome-based multi-drug delivery system will be developed, loading simultaneously two anti-Mycobacterium tuberculosis-drugs, formed by different liposomes glued together in “multi-compartment” clusters. The innovation 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 anti-tuberculosis (TB)-therapy. Multicompartment liposomal clusters, with size larger than a single vesicle, have been demonstrated to possess an intrinsic selectivity towards macrophages, thus representing an emerging platform for the intracellular delivery of anti-TB 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 physical-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.

Benefit for the community

The use of a nanocarrier for simultaneous delivery of IS and RIF could increase the efficacy of anti-TB treatment, due to a synergic administration of the two drugs using a drug delivery vector with specific target capability to macrophages, allowing the use a lower drug concentration linked to a reduced time of therapy regimen and, consequently, to a greater patient compliance. It is expected that multi-compartment liposomal nanovector will be more effective in the therapeutic because they allow the simultaneous delivery of the anti-tubercolar drugs, according to multi-drug treatment, fundamental for tuberculosis care. The drug-entrapped liposomes could fulfill the dual purpose of pulmonary drug delivery and alveolar stabilization due to anti-atelectatic effect of the phospholipids, which can improve the reach of antitubercular drugs to the alveoli.

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