Flumequine-loaded titanate nanotubes as antibacterial agents for aquaculture farms

Tarek Baati; Mounir Ben Brahim; Abir Salek; Mouna Selmi; Leila Njim; Polona Umek; Aicha Aouane; Mohamed Hammami; Karim Hosni

doi:10.1039/d1ra08533f

Flumequine-loaded titanate nanotubes as antibacterial agents for aquaculture farms

RSC Adv. 2022 Feb 17;12(10):5953-5963. doi: 10.1039/d1ra08533f. eCollection 2022 Feb 16.

Authors

Tarek Baati¹, Mounir Ben Brahim¹, Abir Salek¹, Mouna Selmi¹, Leila Njim², Polona Umek³, Aicha Aouane⁴, Mohamed Hammami¹, Karim Hosni¹

Affiliations

¹ Laboratoire des Substances Naturelles, Institut National de Recherche et d'Analyse Physico-chimique, Biotechpôle Sidi Thabet 2020 Tunisia tarek.baati@gmail.com +216 71 537 666.
² Service d'Anatomie Pathologique, CHU de Monastir, Université de Monastir Tunisia.
³ Jožef Stefan Institute Jamova cesta 39 SI-1000 Ljubljana Slovenia.
⁴ Centre de Microscopie Electronique, IBDML campus Luminy Marseille 13000 France.

Abstract

Flumequine (FLUM), a quinolone-derived antibiotic is one of the most prescribed drugs in aquaculture farms. However, its intensive use becomes worrisome because of its environmental risks and the emergence of FLUM-resistant bacteria. To overcome these problems we propose in this study the encapsulation and the delivery of FLUM by titanate nanotubes (TiNTs). Optimal FLUM loading was reached by suspending the dehydrated powder nanomaterials (FLUM : TiNTs ratio = 1 : 5) in ethanol. The drug entrapment efficiency was calculated to be 80% approximately with a sustained release in PBS at 37 °C up to 5 days. Then FLUM@TiNTs was evaluated for both its in vitro drug release and antimicrobial activity against Escherichia coli (E. coli). Spectacularly high antibacterial activity compared to those of free FLUM antibiotic was obtained confirming the efficiency of TiNTs to protect FLUM from rapid degradation and transformation within bacteria improving thereby its antibacterial effect. Indeed FLUM@TiNTs was efficient to decrease gradually the bacterial viability to reach ≈5% after 5 days versus ≈75% with free FLUM. Finally, the ex vivo permeation experiments on sea bass (Dicentrachus labrax) intestine shows that TiNTs act to increase the intestinal permeation of FLUM during the experiment. Indeed the encapsulated FLUM flux increased 12 fold (1.46 μg cm² h^-1) compared to the free antibiotic (0.18 μg cm² h^-1). Thanks to its physical properties (diameter 10 nm, tubular shape…) and its high stability in the simulated intestinal medium, TiNTs are easy internalized by enterocytes, thus involving an endocytosis mechanism, and then improve intestinal permeation of FLUM. Taken together, FLUM@TiNTs hold potential as an effective approach for enhancing the antimicrobial activity of FLUM and pave the way not only for future pharmacokinetic studies in the treatment and targeting of fish infections but also for instating of novel strategies that overcome the challenges associated with the abusive use of antibiotics in fish farming.