Synthesis, Characterization, and in Vitro Drug Delivery Capabilities of (Zn, Al)-Based Layered Double Hydroxide Nanoparticles

There is an urgent need for the development of alternative strategies for effective drug delivery to improve the outcome of patients suffering from deadly diseases such as cancer. Nanoparticles, in particular layered double hydroxide (LDH) nanoparticles, have great potential as nanocarriers of chemotherapeutic molecules. In this study, we synthesized (Zn, Al)-LDH nanoparticles and report their enhanced pH-dependent stability in comparison to the commonly used (Mg, Al)-LDH nanoparticles. Fluorescein isothiocyanate (FITC) and valproate (VP) were intercalated into (Zn, Al)-LDH nanoparticles to study cellular uptake, biocompatibility, and drug delivery capabilities using cultured pancreatic adenocarcinoma BxPC3 cells. Fluorescence measurements indicated that FITC-intercalated LDH nanoparticles showed a greater degree of energy-dependent uptake rather than passive uptake by BxPC3 cells, especially at high concentrations of nanoparticles. Tetrazolium-based colorimetric assays indicated that BxPC3 cells treated with VP-intercalated LDH nanoparticles showed a significant reduction in cell viability along with about 30-fold reduction in IC₅₀ compared to the drug alone. In contrast, the non-drug-intercalated LDH nanoparticles did not affect the cell viability indicating very low innate cytotoxicity. Our research indicates that the superior properties of (Zn, Al)-LDH nanoparticles make them ideal candidates for further development as in vivo chemotherapy drug delivery agents.