Site Model

santé agro matière

Projet financé par l'IBSAM


Antibacterial effect and DNA delivery using a combination of an arsonium-containing lipophosphoramide with an N-heterocyclic carbene-silver complex – Potential benefits for cystic fibrosis lung gene therapy

AUTEURS : A. Mottais⁠, M. Berchel⁠, Y. Sibiril⁠, V. Laurent⁠, D. Gill⁠, S.Hyde⁠, P.A. Jaffrès⁠b, T. Montier⁠, T. Le Gall

Laboratoires de l’IBSAM :

  • Univ. Brest, INSERM UMR 1078, CHRU Brest
  • Univ. Brest, CEMCA UMR CNRS 6521

CITATION: Inter. J. Pharm., 2018, 536, 29-41
DOI: 10.1016/j.ijpharm.2017.11.022

Dans ce travail nous décrivons l’association de composés amphiphiles cationiques ayant des propriétés bactéricides avec des carbènes de l’argent également connus pour leurs propriétés bactéricides. L’association des deux, déposée sur des cultures bactériennes par aérosolisation conduit à un effet synergique. Ce mode d’administration par aérosolisation est des plus appropriés pour une administration dans les poumons et permet simultanément la délivrance d’acides nucléiques au niveau des cellules eucaryotes.

Cystic Fibrosis (CF), the most common chronic genetic disorder among the Caucasian population, is a life-threatening disease mainly due to respiratory failures resulting from chronic infections and inflammation. Although research in the pharmacological field has recently made significant progress, gene therapy still remains a promising strategy to cure CF, especially because it should be applicable to any patient whatever the mutation profile.
Until now, little attention has been paid to bacterial lung infections with regard to gene delivery to the airways; yet, this could greatly impact on the success of gene therapy. Previously, we have reported arsonium-containing lipophosphoramides as poly-functional nanocarriers capable of simultaneous antibacterial action against Gram-positive bacteria and gene transfer into eukaryotic cells. In the present work, we show that such nanoparticles can also be combined with an N-Heterocyclic carbene-silver complex in order to extend the spectrum of antibacterial activity, including towards the Gram-negative Pseudomonas aeruginosa. Importantly, this is demonstrated not only using standard in vitro protocols but also a clinically-relevant aerosol delivery method. Furthermore, antibacterial effects are compatible with efficient and safe gene delivery into human bronchial epithelial cells. The poly-functionality of combinations of such chemical compounds may thus show benefits for CF lung gene therapy