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

Publication date: 30 January 2018 Source:International Journal of Pharmaceutics, Volume 536, Issue 1 Author(s): Angélique Mottais, Mathieu Berchel, Yann Sibiril, Véronique Laurent, Deborah Gill, Stephen Hyde, Paul-Alain Jaffrès, Tristan Montier, Tony Le Gall 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...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research