Valproate intercalated in layered double hydroxides: Synthesis, characterization, release kinetics and biocompatibility studies

Abstract

Layered double hydroxides (LDHs) are biocompatible materials with excellent anion exchange properties, making them suitable for use as drug carriers by incorporating the drug in its anionic form within their layered structure. In this study, an LDH was synthetized through ion exchange with valproate (VAL), an anticonvulsant drug, using an LDH with nitrate as the parent material. The resulting LDH-VAL sample underwent a comprehensivemulti-technique characterization using XRD, TG-DSC, TEM, SEM, EDS, FTIR, XPS and zeta potential measurements. Dissolution kinetics and VAL release kinetics in an ample range of pH (3–9), along with biological assays to test biocompatibility, were also performed. All techniques confirmed the successful intercalation of the drug into the LDH structure, displacing all the nitrate ions of the parent material and increasing the basal spacing d003 from 8.8 Å to 18.3 Å. VAL release in NaCl and physiological buffer solutions was incongruent with LDH dissolution, clearly indicating that VAL release was controlled by an ion exchange process. In 0.9 % NaCl solutions, 90–100 % of VAL was released with only 15–20 % of LDH dissolution, and in buffer solutions 100 % of VAL was released with, at the most, 30 % of LDH dissolution. Biological assays, including lactate dehydrogenaseactivity, serum calcium concentration and histological analysis of blood samples, confirmed that the prepared LDH-VAL is a biocompatible material with a potential use as a nanodrug carrier.