Structural and morphological aspects of (fluoro)quinolone delivery by layered double hydroxide nanoparticles

Abstract

Layered double hydroxides (LDHs) have been proposed as delivery systems (DSs) of (fluoro)quinolones (QLNs) to overcome their low bioavailability and to prevent the emergence of resistant bacteria. Both LDH-DS synthesis as nanoparticles (NPs) and QLN interactions with the metal ions that constitute the layers are essential to improve their physicochemical, biopharmaceutical and antimicrobial properties. Here, LDH-DSs containing the basic form of nalidixic acid (Nal), used as a probe, were obtained by coprecipitation at variable and constant pH (LDH-Nal-pHvar and LDH-Nal-pHcte, respectively). For both syntheses, LDH NPs containing Nal anions (LDH-Nal-NPs), with sizes between 30 and 40 nm, were obtained. A coordination compound (Mg(Nal)₂·4H₂O, Mg(Nal)₂) was also concurrent for LDH-Nal-pHcte, which modulated the drug release profile and antimicrobial properties of the LDH-Nal-NPs. Thus, Nal release from LDH-Nal-pHvar was produced mainly by anion exchange. The best fits, obtained for the Higuchi model, showed rate constants dependent on the exchanging anions (k_H = 0.88 and 1.53 for NaCl 0.9% and buffer phosphate 0.05 M, pH = 7.4, respectively). The nanometric size of LDH-Nal-pHvar as well as its faster release rate allowed a minimum inhibitory concentration decrease (MIC = 32 μg mL⁻¹) compared to the pure drug (MIC = 128 μg mL⁻¹). Instead, the presence of Mg(Nal)₂ in LDH-Nal-pHcte led to a more sustained and media independent Nal release, but a lower MIC (64 μg mL⁻¹) than LDH-Nal-pHvar.