NGUYEN, Phuoc Vinh; AUBRY, Clémentine; BOUDAOUD, Narimane; GAUBERT, Alexandra; LANGLOIS, Marie-Hélène; MARCHIVIE, Mathieu; GAUDIN, Karen; ARPIN, Corinne; BARTHÉLÉMY, Philippe; KAUSS, Tina

doi:10.3390/pharmaceutics14020299

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NGUYEN, Phuoc Vinh
Acides Nucléiques : Régulations Naturelle et Artificielle [ARNA]

AUBRY, Clémentine
Acides Nucléiques : Régulations Naturelle et Artificielle [ARNA]

BOUDAOUD, Narimane
Acides Nucléiques : Régulations Naturelle et Artificielle [ARNA]

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Article de revue

Ce document a été publié dans

Pharmaceutics. 2022, vol. 14, n° 2, p. 299

MDPI

Résumé en anglais

Antibiotic resistance has become a major issue in the global healthcare system, notably in the case of Gram-negative bacteria. Recent advances in technology with oligonucleotides have an enormous potential for tackling this problem, providing their efficient intrabacterial delivery. The current work aimed to apply this strategy by using a novel nanoformulation consisting of DOTAU, a nucleolipid carrier, in an attempt to simultaneously deliver antibiotic and anti-resistance oligonucleotides. Ceftriaxone, a third-generation cephalosporin, was formulated with DOTAU to form an ion pair, and was then nanoprecipitated. The obtained solid nanocapsules were characterized using FT-IR, XRD, HPLC, TEM and DLS techniques and further functionalized by the anti-resistance ONα sequence. To obtain an optimal anti-resistance activity and encapsulation yield, both the formulation protocol and the concentration of ONα were optimized. As a result, monodispersed negatively charged nanoparticles of CFX–DOTAU-ONα with a molar ratio of 10:24:1 were obtained. The minimum inhibitory concentration of these nanoparticles on the resistant Escherichia coli strain was significantly reduced (by 75%) in comparison with that of non-vectorized ONα. All aforementioned results reveal that our nanoformulation can be considered as an efficient and relevant strategy for oligonucleotide intrabacterial delivery in the fight against antibiotic resistance< Réduire

Mots clés en anglais

oligonucleotides

antibiotic resistance

solid nanoparticles

nanocapsules

ESBL-producing E. coli

nucleolipid

nucleic acids

CTX-M15 ß-lactamase

DOI

http://dx.doi.org/10.3390/pharmaceutics14020299

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