Layered double hydroxide-based nanocarriers for drug delivery

Abstract

Biocompatible clay materials have attracted particular attention as the efficient drug delivery systems (DDS). In this article, we review developments in the use of layered double hydroxides (LDHs) for controlled drug release and delivery. We show how advances in the ability to synthesize intercalated structures have a significant influence on the development of new applications of these materials. We also show how modification and/or functionalization can lead to new biotechnological and biomedical applications. This review highlights the most recent progresses in research on LDH-based controlled drug delivery systems, focusing mainly on: (i) DDS with cardiovascular drugs as guests; (ii) DDS with anti-inflammatory drugs as guests; and (iii) DDS with anti-cancer drugs as guests. Finally, future prospects for LDH-based drug carriers are also discussed.

Figure 1

Schematic representation of the structure of layered double hydroxides (LDHs).

Figure 2

Reaction routes to incorporate biomolecules into layered nanomaterials (a) intercalation; (b) exfoliation-restacking; (c) pillaring reaction. Reprinted with permission from [41] (Copyright 2009 Royal Society of Chemistry).

Figure 3

Release profiles for (a) diclofenac at pH 4 and pH 7 and (b) gemfibrozil at pH 4 and pH 7. Reprinted with permission from [57] (Copyright 2001 Royal Society of Chemistry).

Figure 4

Supramolecular structural model of Cpl–LDH. Reprinted with permission from [58] (Copyright 2006 Elsevier).

Figure 5

Release profiles of Cpl from Cpl–LDH in buffer solutions at different pH values Reprinted with permission from [58] (Copyright 2006 Elsevier).

Figure 6

In vitro Low molecular weight heparin (LMWH) release curves from (a) LMWH20–LDH; (b) LMWH100–LDH; (c) physically mixed powder of heparin sodium salt and Cl–LDH (1/8 weight ratio). In (a) and (b), the solid and dashed curves represent the predictions of the modified Freundlich and parabolic diffusion model, respectively. Reprinted with permission from [59] (Copyright 2008 American Chemical Society).

Figure 7

Release profile of statin drugs for (a) pravastatin and (b) fluvastatin based LDH systems under various physiological conditions. Reprinted with permission from [60] (Copyright 2009 American Chemical Society).

Figure 8

X-ray diffraction patterns of (a) MgAl–LDH–NO₃; (b) MgAl–LDH–ibuprofen; (c) MgAl–LDH–diclofenac; and (d) MgAl–LDH–indomethacin. Reprinted with permission from [65] (Copyright 2005 American Chemical Society).

Figure 9

(Left) Scanning electron microscopy (SEM) (A) and transmission electron microscopy (TEM) (C) of metal oxide hollow nanospheres obtained after calcinations of LDH-NCs (nanocrystals)/central nervous system (CNS) composite and SEM (B) and TEM (D) of ibuprofen (IBU)-LDH hollow nanospheres after reconstruction; (Right) In vitro release profile of IBU from IBU-LDH hollow nanospheres in a buffer solution pH 7.0. The inset shows the release profiles from IBU–LDH nanoplates (■) and IBU sodium salt (▲) under the same conditions. Modified with permission from [42] (Copyright 2009 American Chemical Society).

Figure 10

(Left) SEM images of MA-IBU-C (a) and MA-IBU-H-i samples with i = 18 h (b), 36 h (c) and 72 h (d); (Right) Release profiles of IBU from MA-IBU-C (■), MA-IBU-H-18 (□), MA-IBU-H-36 (▲) and MA-IBU-H-72 (∆) in pH 7.45 PBS. Modified with permission from [43] (Copyright 2010 American Institute of Chemical Engineers).

Figure 11

Release curves of DIK from ZnAl–LDH–DIK under different conditions. Reprinted with permission from [74] (Copyright 2011 Elsevier).

Figure 12

The effect of methotrexate MTX–LDH on normal (Left) and tumor (Right) cell growth at the concentration of 5.0 μg·mL⁻¹. Reprinted with permission from [48] (Copyright 2004 Elsevier).

Figure 13

Cellular accumulation of free MTX molecules in MNNG/HOS cells treated with either MTX (○) or MTX–LDH (●). (A) Cell viability/cytotoxicity of MNNG/HOS cells treated with LDHs (▲), MTX (○), and MTX–LDH (●), as monitored by trypan blue exclusion, with respect to drug concentration (B). Reprinted with permission from [50] (Copyright 2006 American Chemical Society).

Figure 14

(a) Cumulative release of MTX from MgAl–LDH–MTX matrix as a function of time and (b) the release data fitted to the first order kinetics model. Reprinted with permission from [92] (Copyright 2013 Elsevier).

Figure 15

Release profiles of 5-Fu from 5-Fu/CMCD–LDH composite in phosphate-citrate buffer solution at different pH values. Reprinted with permission from [96] (Copyright 2010 American Chemical Society).

Figure 16

Resonance structure of doxifluridine (DFUR) and the synthetic strategy for DFUR–LDH hybrids. Modified with permission from [17] (Copyright 2010 Elsevier).

Figure 17

(Left) SEM images of DFUR–LDHr1.7p7.2 (A,B) and DFUR–LDHr2.0p9.5 (C,D); (Right) Release profiles of DFUR-LDHrip7.2 (i = 1.7, 2.1, 2.9) and DFUR–LDHr2.0p9.5. Modified with permission from [17] (Copyright 2010 Elsevier).

Figure 18

Release profiles (a) for CPT from a CPT–LDH composite and the physical mixture at pH 4.8 and pH 7.2 (■: composite, pH 4.8; ●: composite, pH 7.2; ▲: physical mixture, pH 4.8; ▼: physical mixture, pH 7.2) and linear regression curves of release data fitted with the pseudo-second-order kinetic model at pH 4.8 (b1) and pH 7.2 (b2) (t refers to release time, X_t refers to percentage releases, q_t refers to release amount at any time (t)). Modified with permission from [99] (Copyright 2010 Elsevier).

Figure 19

T₁-weighted MRI signal intensity and signal to noise ratio (SNR) of liver (a) and spleen (b) before (control) and after intravenous administration of LDH–Gd/Au nanocomposite/physiological saline at various intervals (dose: 3.1 mg or 197.1 mmol·Gd/kg). Reprinted with permission from [103] (Copyright 2013 Elsevier).