Risedronate functionalized layered double hydroxides nanoparticles with bone targeting capabilities

Layered double hydroxides nanoparticles (LDH-NPs) are increasingly studied as drug nanocarriers for cellular delivery. Nevertheless, stable functionalizations providing targeting capabilities without disrupting the size of the carriers are necessary to achieve optimized performance. Here, LDH-NPs were functionalized with risedronate (Ris) to improve the osteotropicity of the nanocarriers without altering the nanosized-distribution. Ris is a nitrogen containing bisphosphonate with rich acid-base reactivity that can lead Ris functionalized LDH-NPs also as pH-responsive drug nanocarriers. The current work is focused on the strategy to synthesize functionalized LDH-NPs with a maximum adsorption and a minimum intercalation of Ris while maintaining their nanosize. The speciation and interactions of Ris at the surface of LDH-NPs were analyzed using Raman microscopy whereas the functionalization stability and size distribution were checked in simulated biological media. Finally, pH sensitivity and hydroxyapatite binding capacity of Ris functionalized LDH-NPs were evaluated. HIRis(3-) anions were incorporated to the LDH-NPs surface with high affinity providing with a negative zeta potential that controlled the size at around 100 nm. The size of Ris functionalized LDH-NPs was not affected by the high ionic strength or the presence of proteins in simulated biological media. Further, the functionalization was stable against protein adsorption and anionic exchange. As expected, Ris functionalized LDH-NPs are bioresponsive with a high sensitivity for pH changes and specific affinity for hydroxyapatite, which makes them appealing drug nanocarriers for new bone therapies. (C) 2017 Elsevier B.V. All rights reserved.