A systematic approach to the synthesis of LDH nanoparticles by response surface methodology

Abstract

The customization of the properties of layered double hydroxides nanoparticles (LDH-NPs) is essential to optimize their design innovative systems for biomedical applications. Response surface methodologies (RSMs), a collection of mathematical and statistical techniques that allows multivariate optimization of processes, are a useful tool for LDH-NPs customization. In this work, RSMs were used to study the synthesis parameters governing the size and composition of Mg[sbnd]Al LDH-NPs (Mg/Al = 3) labeled with fluorescein isothiocyanate (FITC2 −) and prepare customized samples for biological assays. The influence of [Al3 +], [OH−]/[Mg2 ++ Al3 +], 2[FITC2 −]/[Al3 +] and time of the hydrothermal treatment (tHT) was determined by a Box-Behnken experimental design (BBD). The experimental responses were hydrodynamic diameter (dH), polidispersity index (PI) and FITC2 − content (%FITC), and their dependence with the synthesis variables was described by polynomial model. The model correlated high [Al3 +] with large dH values due to aggregation processes, while tHT was the main variable governing the size of the disaggregated units. These results were explained based on the precipitation and recrystallization mechanisms of LDH-NPs. The mathematical model derived from the BBD accurately predicted the synthesis conditions to obtain LDH-NPs with controlled dH values between 50 and 200 nm, minimum PI and tunable %FITC. The convenience of the synthesized LDH-NPs for biological assays were tested in experiments with giant unilamellar vesicles and cell cultures monitored by confocal microscopy.