Enhancement of lung gene delivery after aerosol: a new strategy using non-viral complexes with antibacterial properties

Author:

Mottais Angélique1,Le Gall Tony1,Sibiril Yann1,Ravel Julian1,Laurent Véronique1,d’Arbonneau Frédérique1,Montier Tristan1

Affiliation:

1. “Gene Transfer and Gene Therapy” Team, INSERM UMR 1078; IBSAM; Laboratoire de Génétique Moléculaire et Histocompatibilité, CHRU Brest; UFR Médecine et Sciences de la Santé, 22 avenue Camille Desmoulins, Brest 29238, France

Abstract

The pathophysiology of obstructive pulmonary diseases, such as cystic fibrosis (CF), leads to the development of chronic infections in the respiratory tract. Thus, the symptomatic management of the disease requires, in particular, repetitive antibiotherapy. Besides these antibacterial treatments, certain pathologies, such as CF or chronic obstructive pulmonary disease (COPD), require the intake of many drugs. This simultaneous absorption may lead to undesirable drug interactions. For example, Orkambi® (lumacaftor/Ivacaftor, Vertex), a pharmacological drug employed to treat F508del patients, cannot be used with antibiotics such as rifampicin or rifabutin (rifamycin family) which are necessary to treat Mycobacteriaceae. As far as gene therapy is concerned, bacteria and/or biofilm in the airways present an additional barrier for gene transfer. Thus, aerosol administration of nanoparticles have to overcome many obstacles before allowing cellular penetration of therapeutic compounds. This review focusses on the development of aerosol formulations adapted to the respiratory tract and its multiple barriers. Then, formulations that are currently used in clinical applications are summarized depending on the active molecule delivered. Finally, we focus on new therapeutic approaches to reduce possible drug interactions by transferring the antibacterial activity to the nanocarrier while ensuring the transfection efficiency.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry,Biophysics

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