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 ironbased layered double hydroxides (LDHs) with molar ratio M 2+ /(Fe 3+ + Al 3+ ) equal to 2, Fe 3+ /Al 3+ equal to 1, and chloride anions as charge-compensating ion (abbreviated Mg 4 FeAl-Cl and Zn 4 FeAl-Cl) prepared by the coprecipitation method. The higher structural organization of Zn 4 FeAl-Cl in comparison to Mg 2+ 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 M 4 FeAl-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 Mg 4 FeAl-Cl in the extracellular matrix compared to zinc LDH. Considering the positive biocompatibility results obtained for M 4 II FeAl-LDH materials, experiments were conducted to intercalate the anti-inflammatory naproxen, as a model drug, into the iron-based LDHs (M 4 II FeAl-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 Zn 2+ (around 1%). Iron-based LDHs have great potential for medical and technological applications as local drug delivery biomaterials exhibiting biocompatibility and biointegration properties.

Toxicity of Zn-Fe Layered Double Hydroxide to Different Organisms in the Aquatic Environment

“…The samples for the toxicity tests were prepared by the addition of an appropriate amount of the Zn-Fe LDHs into the culturing medium for each test organism. The wide concentration ranges of Zn-Fe LDHs used in this work were chosen based on related applications reported in the scientific literature [ 10 , 12 , 13 , 14 , 15 ]. Appropriate volumes specified for the toxicity tests were prepared by adding the Zn-Fe LDHs catalyst into the test medium through an automatic pipette forming catalyst + test medium suspensions.…”

“…Their high specific surface area, catalytic ability, anion exchange capability, thermal stability, tunability, as well as flexibility in their interlayer spaces [ 2 , 7 ] render them high performance and unique materials. Hence LDHs found their applications in various fields such as biology [ 1 , 6 ], electrochemistry [ 6 , 8 , 9 ], photochemistry [ 10 , 11 ], pharmacy and medicine [ 1 , 12 ]. They are also used as additives in polymers, adsorbents in water purification systems [ 13 ] and, in particular, as catalytic nanomaterials or catalyst supports [ 10 , 14 , 15 , 16 , 17 ].…”

Design of 3D multi-layered electrospun membranes embedding iron-based layered double hydroxide for drug storage and control of sustained release

“…LDH matrix by its own is commercialized as the antacid TALCID™, composed of magnesium and aluminium cations and intercalated with carbonate anions. [10] Thanks to the biocompatibility of LDHs compositions (verified in vitro and in vivo [11][12][13][14][15][16][17]), their effective interactions with biological membranes, high encapsulation efficiency, and capacity to prolong drug release, these materials are promising to be applied as vehicles for drug storage and delivery. [18][19][20] In this way, many species such as aminoacids, [21] anti-inflammatories [22] and cancer drugs [23] have been intercalated between the LDHs layers.…”

Mixed Oxide Layered Double Hydroxide Materials: Synthesis, Characterization and Efficient Application for Mn2+ Removal from Synthetic Wastewater

“…The study was made regarding the possibilities of incorporation of an organic anion (phenyl-alanine amino acid anion) between the cationic layers, by using three different methods: Ionic exchange, direct coprecipitation and structure reconstruction after calcination at 400 • C. It is known that LDH is an active adsorbent, but studies on the effects of different parameters on the efficiency of eliminating Mn 2+ have not been adequately explored. Figueiredo et al [15] showed that the iron-based LDHs Zn 4 FeAl and Mg 4 FeAl, constituted by a high level of the endogenous iron ions, are potential candidates used in the therapeutic field. Benício et al [16] synthesized and characterized layered double hydroxides (MgAl LDHs, MgFe LDHs and MgAlFe LDHs) containing phosphate anions.…”

“…It is known that LDH is an active adsorbent, but studies on the effects of different parameters on the efficiency of eliminating Mn 2+ have not been adequately explored. Figueiredo et al [ 15 ] showed that the iron-based LDHs Zn 4 FeAl and Mg 4 FeAl, constituted by a high level of the endogenous iron ions, are potential candidates used in the therapeutic field. Benício et al [ 16 ] synthesized and characterized layered double hydroxides (MgAl LDHs, MgFe LDHs and MgAlFe LDHs) containing phosphate anions.…”