Mycobacterium abscessus infections in people with cystic fibrosis (CF) are particularly difficult to treat. They require prolonged antibiotic therapies, often with limited success and serious side effects. This is why new treatment strategies are urgently needed.

In previous studies (FFC#17/2013, FFC#14/2017, FFC#21/2019, and FFC#13/2022), researchers developed bioactive liposomes which were capable to strongly enhance macrophages’ antimicrobial response, leading to intracellular killing of MDR (myco)bacteria, while limiting the potentially pathogenetic inflammatory response.

Liposomes are also a well-known efficient drug delivery system and have the ability to reduce drug systemic toxicity concentrating them into the target organ.

In this new project, researchers will use Microfluidic technique to optimize the production, stability, and homogeneity of the liposomes while maintaining the same bioactive properties. Liposomes will be further developed by encapsulating Amikacin, Clarithromycin or Azithromycin to combine the host-directed action with the pathogen-directed action in a single, more active, and clinically exploitable therapeutic formulation.

The therapeutic value of the antibiotic-loaded liposomes will be assessed on human macrophages from both healthy donors and people with CF, infected in vitro with M. abscessus. The most promising formulation will then be tested in vivo in animal models, with the support of the CFaCore facility of FFC Ricerca.

The results of this project will pave the way for future preclinical and clinical development of these formulations. Liposomal therapies could provide an effective alternative to current, often ineffective, antibiotic treatments and may also potentially shorten the duration of therapy.