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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 (kH = 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.