Co‐delivery of Doxycycline, Florfenicol and Silver Nanoparticles using Alginate/Chitosan Nanocarriers

Abstract The overuse of antibiotics has led to the sharp increase of antibiotic‐resistant bacteria that can consequently transmit and cause hard‐to‐cure human diseases. To deal with this problem, nano drug delivery systems have been widely researched. This report focuses on developing an Alginate/Chitosan‐based nanosystem that carried simultaneously Doxycycline (DOX), Florfenicol (FLO), and silver nanoparticles (AgNPs). The optimal Alginate/Chitosan ratio of 3 : 2 (w/w) created the most stable nanocarrier system. The fabricated DOX‐FLO@AgNPs had a spherical shape with a small size of about 20 nm and could release slowly DOX and FLO at pH of 7.4 and 5.0. In vitro drug release kinetics of DOX and FLO from DOX‐FLO@AgNPs fitted best to the Weibull or Higuchi model by the mechanism of the Fickian or non‐Fickian diffusion. The nanosystem of DOX‐FLO@AgNPs had much lower IC 50 of 0.012±0.001 and 0.08±0.005 μg/mL against E. coli and B.subtilis , respectively, than the conventional form. The FIC 50 value of smaller than 0.5 μg/mL for 5 out of 6 tested bacteria also indicated the synergistic effect of each component in this antibiotic combination. Moreover, the cytotoxicity assay confirmed the viability of 96.4±2.3 % for vero cell line that exposured to the treatment dose. Therefore, these findings strongly suggest that the DOX‐FLO@AgNPs formulation is promising for combined antibiotic drug delivery and silver nanoparticles, and will be worth investigating for further in vivo potential.