Iron-Based Layered Double Hydroxide Implants: Potential Drug Delivery Carriers with Tissue Biointegration Promotion and Blood Microcirculation Preservation

Abstract

This work explores the synthesis, physicochemical characterization, and in vivo biocompatibility of iron-based layered double hydroxides (LDHs) with molar ratio M2+/(Fe3+ + Al3+) equal to 2, Fe3+/Al3+ equal to 1, and chloride anions as charge-compensating ion (abbreviated Mg4FeAl-Cl and Zn4FeAl-Cl) prepared by the coprecipitation method. The higher structural organization of Zn4FeAl-Cl in comparison to Mg2+ analogous material was noticed by X-ray diffraction and scanning electron microscopy images. Biocompatibility of LDH was evaluated by intramuscular implantation in rats. Tablets of M4FeAl-Cl (M = Mg, Zn) were readily identified macroscopically after 7 and 28 days of implantation, denoting slow dissolution in the internal medium; adjacent to the tablets, blood flow was preserved without tortuosity or pathological dilatations, according to the Sidestream Dark Field Imaging technique. The histological analysis showed no inflammatory response and the presence of angiogenesis and tissue remodeling with the reconstruction of the extracellular matrix and cells around the tablets, besides the induction of collagen type-I formation. Prussian blue histochemical reaction suggested higher solubility of Mg4FeAl-Cl in the extracellular matrix compared to zinc LDH. Considering the positive biocompatibility results obtained for M4IIFeAl-LDH materials, experiments were conducted to intercalate the anti-inflammatory naproxen, as a model drug, into the iron-based LDHs (M4IIFeAl-NAP). The release profile of NAP in phosphate buffer showed 90% of the drug delivered after about 80 h. However, divalent metal leaching was verified mainly for Mg-LDH (around 50%) when compared to Zn2+ (around 1%). Iron-based LDHs have great potential for medical and technological applications as local drug delivery biomaterials exhibiting biocompatibility and biointegration properties.