Fabrication of a nano-drug delivery system based on layered rare-earth hydroxides integrating drug-loading and fluorescence properties

Article abstract of DOI:10.1039/c6dt01875k

We demonstrate the first example of intercalation of naproxen (abbr. NPX) into layered europium hydroxide (LEuH) and investigate the structure, chemical composition, thermostability, morphology, luminescence properties, cytotoxic effect, and controlled-release behaviors. Different deprotonation degrees lead to NPX-LEuH composites with diverse structures (horizontal or vertical arrangement), and the thermal stability of organics is enhanced after intercalation. The Eu³⁺ luminescence in NPX-LEuH composites is enhanced, especially for the NPX-LEuH-1: 0.5 composite. The content of naproxen in the intercalation material can be confirmed by HPLC. The cytotoxic effect of LEuH is observed with a sulforhodamine B (SRB) colorimetric assay, which reveals that the LEuH has low cytotoxic effects on most cells. In addition, the NPX-LEuH nanocomposites can control the release of NPX in Na₂HPO₄-NaH₂PO₄ buffer solution at pH 6.86 and 37 °C, and the complete release needs about 200 min. The release mechanism can be ascribed to the ion-exchange reaction between NPX and HPO₄^2-/H₂PO₄^- in bulk solution. The ion-exchange velocity is fast at the beginning and slows down gradually with the exchange reaction. The construction of LRH composites with drug molecules provides a beneficial pathway for preparing a nano-drug delivery system based on LRHs integrating drug-loading and fluorescence properties.

Full text of DOI:10.1039/c6dt01875k

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Fabrication of a nano-drug delivery system based
on layered rare-earth hydroxides integrating
drug-loading and fluorescence properties
Cite this: Dalton Trans., 2016, 45,
12137
Qingyang Gu,* Wen Chen, Fei Duan and Ruijun Ju
We demonstrate the first example of intercalation of naproxen (abbr. NPX) into layered europium hydro-
xide (LEuH) and investigate the structure, chemical composition, thermostability, morphology, lumine-
scence properties, cytotoxic effect, and controlled-release behaviors. Different deprotonation degrees
lead to NPX–LEuH composites with diverse structures (horizontal or vertical arrangement), and the
thermal stability of organics is enhanced after intercalation. The Eu3+ luminescence in NPX–LEuH com-
posites is enhanced, especially for the NPX–LEuH-1 : 0.5 composite. The content of naproxen in the
intercalation material can be confirmed by HPLC. The cytotoxic effect of LEuH is observed with a sulfor-
hodamine B (SRB) colorimetric assay, which reveals that the LEuH has low cytotoxic effects on most cells.
In addition, the NPX–LEuH nanocomposites can control the release of NPX in Na2HPO4–NaH2PO4 buffer
solution at pH 6.86 and 37 °C, and the complete release needs about 200 min. The release mechanism
−
can be ascribed to the ion-exchange reaction between NPX and HPO42−/H2PO4 in bulk solution. The
Received 12th May 2016,
Accepted 1st July 2016
ion-exchange velocity is fast at the beginning and slows down gradually with the exchange reaction. The
construction of LRH composites with drug molecules provides a beneficial pathway for preparing a nano-
drug delivery system based on LRHs integrating drug-loading and fluorescence properties.
DOI: 10.1039/c6dt01875k
www.rsc.org/dalton
host layer.11 Layered double hydroxides (LDHs), as an anionic
type layered material, have shown great promise for the deliv-
1. Introduction
In recent years, increasing attention has been directed toward ery of chemical therapeutics and bioactive molecules to mam-
the investigation of inorganic drug delivery systems for safe malian cells in vitro and in vivo. This system offers high
drug delivery. Inorganic drug delivery systems can allow safe efficiency and drug loading density, as well as excellent protec-
and controlled delivery of various bioagents into targets with tion of loaded molecules from undesired degradation.12 The
high efficiency.1 Both natural and synthetic materials have cationic layered framework of LDHs leads to safe accommo-
been tested and proposed as components of new drug delivery dation of many biologically important molecules including
systems (NDDS) and many efforts have been made to syn- genes or drugs.13,14 Toxicological studies have also found
thesise materials with biological, technological, and mecha- LDHs to be biocompatible compared with other widely used
nical properties for each application in drug delivery.2,3 In nanoparticles, such as iron oxide, silica, and single-walled
recent years, many types of materials including inorganic carbon nanotubes. A plethora of bio-molecules have been
silica,4,5 carbon materials,6,7 and polymeric matrices8,9 have reported to either attach to the surface or intercalate into LDH
been employed as substrates for drug delivery. Among a variety materials through co-precipitation or anion-exchange reaction,
of inorganic materials, layered materials have attracted intense including amino acids, peptides, vitamins, polysaccharides,
interest because of the rich interlayer chemistry.10 The inter- etc.12
calation of guests into inorganic hosts can influence the pro-
Layered rare-earth hydroxides (LRHs) with the general
(RE = rare-earth cations,
perties of both the host layers and gallery guests, especially formula of [RE2(OH)5(H2O)n][Am−
]
1/m
enhancing the chemical, thermal and photolytic stability of Am− = anions),15 as one kind of layered materials with positive
the guests because of a protective environment provided by the layers, have been extensively studied due to their applications
as catalysts,16,17 adsorbents,18 and optical materials.19–21 Con-
cerning intercalation of LRHs, most of the reports described
their anion exchange behaviors and luminescence properties,
while there has been a lack of studies focusing on drug delivery,
Department of Chemical Engineering, Beijing Institute of Petrochemical Technology,
Beijing 102617, China. E-mail: guqingyang@bipt.edu.cn; Fax: +86 10 81292133;
except for our published work concerning the intercalation of
Tel: +86 10 81292133
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amino acids into Eu3+-doped layered gadolinium hydroxide 2.3 Measurement of the released amount of NPX
(LGdH:Eu) taking advantage of the luminescence quenching
effect to obtain luminescence probes to detect certain amino
acids in biological systems.
Firstly, NPX–Na solution (2.0 × 10−5 mol L−1) was prepared by
dissolving 0.2 mmol of NPX and 0.2 mmol of NaOH in
100 mL/0.025 mol L−1 NaHPO4–NaH2PO4 buffer solutions
Naproxen (abbr. NPX), (+)-(S)-2-(6-methoxynaphthalene-2-yl)
(pH = 6.86). The absorbance peaks of NPX–Na were obtained
propanoic acid, is a non-steroidal anti-inflammatory drug fre-
by ultraviolet scanning. Secondly, the standard curve of con-
quently used for the reduction of severe pain, fever, inflam-
centration–absorbance of NPX–Na was obtained at the
maximal absorption band (330 nm), and the testing concen-
mation and stiffness caused by conditions such as
osteoarthritis, rheumatoid arthritis, psoriatic arthritis, gout,
tration was 1.0 × 10−5, 2.0 × 10−5, 2.5 × 10−5, 5.0 × 10−5
and tendonitis, and for the treatment of primary dysmenor-
mol L−1, respectively. Finally, the release kinetic curve of NPX
rhea.22 For drug therapy to be most effective, the desired
from NPX–LEuH was obtained in NaHPO4–NaH2PO4 buffer
pharmacological response must be obtained at the target
solutions at pH 6.86 and 37 °C.
without harmful interactions at other sites,23 which requires
controlled and correct drug dosage. The binding of drug mole-
2.4 Characterization techniques
cules and rare earth ions can detect drug molecules sensitively
by monitoring the luminescence change. In previous research, The powder X-ray diffraction (XRD) patterns were collected by
the intercalation of NPX into LDHs and the controlled release using a Phillips X’pert Pro MPD diffractometer with Cu-Kα
behaviors have been studied,24,25 but there are no reports radiation at room temperature, with a step size of 0.0167°,
about the intercalation of NPX into LRHs and taking advan- scan time of 15 seconds per step, and 2θ ranging from 4.5 to
tage of the luminescence properties to detect drug molecules.
70°. The generator setting was 40 kV and 40 mA. For the small
Herein we intercalate NPX into LEuH to form composites. degrees, the XRD patterns were obtained at room temperature
The luminescence investigation shows that the incorporation with a step size of 0.008° and a scan time of 30 seconds per
of NPX into the LRH layer can sharply enhance the Eu3+ step. Fourier transform infrared (FT-IR) spectra of the samples
luminescence. This method can be applied as a luminescence were recorded on a Nicolet-360 Fourier-Transform infrared
probe to detect NPX in biological systems. In addition, the spectrometer by the KBr method. Scanning electron
NPX–LEuH nanocomposites can control the release of NPX, microscopy (SEM) observations were carried out by using a
which can be used for nano-drug delivery systems.
Hitachi S-4800 microscope at 5.0 kV. Thermo-gravimetric and
differential thermal analysis (TG-DTA) measurements were
performed with a ZRY-2P thermal analyzer under air. Lumine-
scence spectra were obtained on
spectrofluorimeter.
a
Hitachi F-4500
2. Experimental section
2.1 Preparation of the NO3–LEuH precursor
The metal ion contents were determined by inductively
coupled plasma atomic emission spectroscopy (ICP-AES,
Jarrel-ASH, ICAP-9000) after the solid products were dissolved
in a 0.1 M HNO3. C, H and N contents were determined by
using an Elementar vario EL elemental analyzer. The chemical
formulae of the products were determined based on the
results of ICP and CHN analyses.
The content of naproxen in the intercalation material was
measured by HPLC (Agilent 1260 liquid chromatographic
system, Agilent Technologies Inc., USA) with a Nucleodur
100-5 C18 column (250 × 4.6 mm, 5.0 μm). The detection wave-
length was set at 230 nm, and the analysis was performed at
−
The NO3 type LEuH (NO3–LEuH) was synthesized via a
hydrothermal method as previously reported.19,26 An aqueous
solution containing Eu(NO3)3·6H2O (1 mmol), hexamethylene-
tetramine (HMT, 1 mmol), and NaNO3 (13 mmol), in de-
ionized water (80 mL) was heated at 90 °C for 12 h in a Teflon-
autoclave. After the reaction, the product was filtered, washed,
and vacuum-dried (40 °C for 24 h), obtaining the NO3–LEuH
precipitate.
2.2 Intercalation of NPX into LEuH by the ion exchange
method
−
The ion-exchange reactions between NO3 and the organic ambient temperature. The mobile phase consisted of aceto-
anions were processed at 70 °C in a Teflon-autoclave. Firstly, nitrile, 0.02 M K2HPO3 and triethylamine (60 : 40 : 0.3, v/v/v).
1.26 mmol of NPX and 0.63/0.88/1.26/1.51 mmol of NaOH The pH was adjusted to 4.0 with phosphoric acid, and the flow
(corresponding to a 1 : 0.5/1 : 0.7/1 : 1/1 : 1.2 molar ratio of rate was 1.0 ml min−1
NPX to NaOH) were mixed to obtain solutions (80 ml). The
.
To evaluate the cytotoxic effect of (NO3–LEuH), brain
NO3–LEuH powder (∼0.1 g) was dispersed into the above solu- glioma U87MG cells, breast cancer MDA-MB-435S cells,
tions, and then reacted at 70 °C for 24 h in a Teflon-autoclave. murine brain microvascular endothelial cells (BMVECs), and
The resulting precipitates were collected by filtration, washed human umbilical vein endothelial cells (HUVECs) were seeded
with deionized water, and vacuum-dried at 40 °C for 24 h. The at a density of 6 × 103 cells per well in 96-well culture plates
as-prepared composites are denoted as NPX–LEuH-1 : x, in and cultured for 24 h. The cells were then treated with NO3–
which x is the molar ratio of NaOH to NPX, for example LEuH in the range of 0–100.0 μg ml−1. After incubation for
NPX–LEuH-1 : 0.5 represents the molar ratio of NPX to NaOH another 48 h, the cytotoxic effect was observed with a sulfor-
as 1 : 0.5.
hodamine B (SRB) colorimetric assay. Briefly, the culture
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medium was discarded, and then the cells were fixed with tri-
chloroacetic acid, followed by staining with SRB. Absorbance
values were measured at 540 nm using a microplate reader
(Tecan Infinite F50, Tecan Group Ltd Switzerland).
3. Results and discussion
3.1 Structure analyses of the as-prepared composites
Fig. 1 shows the XRD patterns of the precursor and the formed
composites. For NO3–LEuH (Fig. 1a), a series of strong (00l)
reflections observed at 0.83 and 0.42 nm are characteristics
of a layered phase, showing a basal spacing (dbasal) of 0.83 nm
identical to the previously reported values.19,26 The sharp and
symmetric diffraction peaks indicate a high crystallinity.
Fig. 1b shows the XRD pattern of the NPX–LEuH-1 : 0.5 com-
posite prepared by the ion-exchange method. It has two dbasal
values of 2.23 and 1.50 nm, with series of (00l) reflections at
2.23, 0.97, 0.76, 0.58 nm and 1.50, 0.76, 0.51, 0.39 nm, respec-
tively. For the composite of NPX–LEuH-1 : 0.7 (Fig. 1c), the
dbasal value is 2.32, with series of (00l) reflections at 2.32, 1.17,
0.78, 0.58, 0.47, and 0.40 nm. When the molar ratio of
NPX and NaOH is 1 : 1 and 1 : 1.2 (Fig. 1d and e), there is no
reflection peak in the range of small angle, and the dbasal value
is 0.76/0.75 nm. The 0.32 nm peak arises from the non-basal
(220) reflection that represents the feature of the host layer,27
and it does not change after ion-exchange, which shows the
invariability of the host layer.
Scheme 1 Schematic representation of the proposed arrangement of
the gallery species between the layers.
of a monolayered vertical arrangement and a horizontal
arrangement (Scheme 1b), considering the NPX size of
ca. 1.18 × 0.50 × 0.41 nm3. This may be caused by the partial
deprotonation. The NPX–LEuH-1 : 0.7 composite may corres-
pond to a monolayered vertical arrangement (Scheme 1c). The
organic guests strongly interact with each other via π–π inter-
actions of naphthalene rings. The basal spacing of the compo-
sites of NPX–LEuH-1 : 1 and NPX–LEuH-1 : 1.2 is around
0.75 nm, which may be ascribed to the OH− intercalated in the
layers (Scheme 1d).
For the NPX–LEuH-1 : 0.5 composite, on the basis of the
layer thickness of LRHs (0.65 nm),19 there exists two gallery
heights, ca. 1.58 nm (= 2.23–0.65) and 0.85 nm (= 1.50–0.65).
This may correspond to two kinds of arrangement structures
Based on ICP, CHN analyses and charge balance consider-
ations, the estimated compositions of the LEuH precursor and
the as-prepared composites are shown in Table 1. The pres-
2−
ence of CO3 may arise from HMT decomposition.28,29 For
the composites of NPX–LEuH-1 : 0.5/0.7, almost half NPX
neutral molecules exist in the compositions apart from partial
deprotonated organics. The ratio of the deprotonated and the
neutral NPX is in agreement with the amount of added NaOH.
For the composites of NPX–LEuH-1 : 1/1.2, the excessive OH−
are intercalated into LEuH and there is little organic content.
These results are in agreement with the XRD patterns.
3.2 FT-IR, SEM and thermal analyses of samples
For NO3–LEuH (Fig. 2a), the sharp and strong peak at
1384 cm−1 is characteristic of the ν3 vibration mode of unco-
ordinated NO3 .
− 30 For NPX (Fig. 2b), the band at 3453/3239 cm−1
is the characteristic absorption of –OH and the band at
1726 cm−1 is the stretching vibration of –CvO. The bands at
1609 cm−1 and 1456 cm−1 are vibration absorptions of the
benzene ring. The bands at 1391 cm−1 and 1261 cm−1 are
ascribed to the bending/stretching and stretching/bending
vibrations of –COOH. 1177 cm−1 is due to the absorption of
the C–O group. The bands at 1026 cm−1 and 860 cm−1 are
ascribed to the νas and νs vibrations of the C–O–C group.22 In
the composites of NPX–LEuH (Fig. 2c–f), the bands at
1551/1558/1549/1540 cm−1 and 1410/1406/1391/1389 cm−1 are
assigned to the νas and νs vibrations of the deprotonated
Fig. 1 XRD patterns of NO3–LEuH (a) and composites of NPX–
LEuH-1 : 0.5 (b, b’), NPX–LEuH-1 : 0.7 (c, c’), NPX–LEuH-1 : 1 (d, d’),
NPX–LEuH-1 : 1.2 (e, e’). The d-values are given in nanometers.
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Table 1 Chemical compositions for LEuH: the precursor and the composites
Wt%, found
Eu
Samples
Chemical formula
C
H
N
NO3–LEuH
Eu(OH)2.50(NO3)0.34(CO3)0.08·0.69H2O
64.14
45.13
59.30
78.67
71.69
0.25
1.63
4.26
3.25
2.32
2.13
2.01
0.10
0.00
0.08
0.01
NPX–LEuH-1 : 0.5
NPX–LEuH-1 : 0.7
NPX–LEuH-1 : 1
NPX–LEuH-1 : 1.2
Eu(OH)2.50(NO3)0.02(C14H13O3)0.48(C14H14O3)0.51·0.47H2O
Eu(OH)2.50(CO3)0.08(C14H13O3)0.34(C14H14O3)0.09·0.07H2O
Eu(OH)2.50(NO3)0.01(C14H13O3)0.07(OH−)0.42·0.30H2O
Eu(OH)2.50(NO3)0.0015(C14H13O3)0.05(OH−)0.45·0.45H2O
49.44
28.63
6.42
4.04
Fig. 3 TG-DTA curves of NO3–LEuH (a), NPX (b), and NPX–LEuH-1 : 0.5
composite.
Fig. 2 FT-IR spectra of NO3–LEuH (a), NPX (b), and composites of
NPX–LEuH-1 : 0.5 (c), NPX–LEuH-1 : 0.7 (d), NPX–LEuH-1 : 1 (e), NPX–
LEuH-1 : 1.2 (f).
SEM images show that the NO3–LEuH precursor (Fig. 4a
and a′) is mainly crystallized into elongated hexahedron plate-
lets. The composites (Fig. 4b–e and b′–e′) retain the hexagonal
morphology and grow into columnar or flower-like aggregates
resembling the LEuH precursor, as observed in our precious
work.19,26
–COO− group. Compared with NPX, the absorption of CvO
shifts to low frequency due to the interaction between host
layers and guest NPX. The bands around 581 cm−1 ascribed to
Eu–O vibrations also verify the formation of the layered
composites.19
3.3 Luminescence of NPX–LEuH composites
For the LEuH precursor (Fig. 5a), typical emission peaks
TG-DTA results indicate the thermal stability after intercala- observed at 580, 589/595, 613, 654, and 698 nm assigned to
tion of organics. Compared with the exothermic peaks at the 5D0–7FJ (J = 0, 1, 2, 3, 4) radiative-relaxational transitions of
499 °C for NPX (Fig. 3b) related to combustion of organics, the Eu3+ are observable. After forming composites, the Eu3+
NPX–LEuH-1 : 0.5 composite (Fig. 3c) shows exothermic peaks luminescence in the NPX–LEuH-1 : 0.5 composite is markedly
at 505 °C. This indicates a slightly heightened thermal stability enhanced. This may be caused by the efficient energy transfer
by 5–6 °C. The weight loss of the composite is much higher between intercalated NPX anions and Eu3+ centers. For the
than the NO3–LEuH (Fig. 3a) but lower than the NPX (Fig. 3b), NPX–LEuH-1 : 0.7/1/1.2 composites, the Eu3+ luminescence
indicating the inclusion of organic guests and the LEuH layer. intensity shows a slight enhancement. This may be interpreted
Hence, the TG-DTA results indicate that the composite has as that the triplet state energy level of organics matches well
5
better thermal stability in comparison with organics.
with the resonant D0 energy level of Eu3+ for composites with
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Fig. 6 HPLC chromatograms of NPX under the measuring conditions:
(A) chromatogram from a standard sample NPX. (B) Choromatogram
from the drug-containing sample NPX–LEuH-1 : 0.5.
Fig. 4 SEM images of precursor NO3–LEuH (a, a’), and composites
NPX–LEuH-1 : 0.5 (b, b’), NPX–LEuH-1 : 0.7 (c, c’), NPX–LEuH-1 : 1 (d, d’),
NPX–LEuH-1 : 1.2 (e, e’).
obtained for the drug containing sample NPX–LEuH-1 : 0.5,
excluding that the peaks of LEuH appear in approximately
2.3–2.6 min, suggesting that the LEuH does not interfere with
the measurement of NPX (Fig. 6B).
To evaluate the cytotoxic effect of NO3–LEuH, brain glioma
U87MG cells, breast cancer MDA-MB-435S cells, murine brain
microvascular endothelial cells (BMVECs), and human umbili-
cal vein endothelial cells (HUVECs) are treated with NO3–
LEuH in the range of 0–100.0 μg ml−1. After incubation for
another 48 h, the cytotoxic effect was observed with a sulforho-
damine B (SRB) colorimetric assay. The survival ratios are cal-
culated using the following formula:
A540 nm for treated cells
A540 nm for control cells
Survival rate% ¼
ꢀ100%
where A540 nm represents the average absorbance value.
As is shown in Fig. 7, all the cells (except BMVECs) display
little cell death even at a high concentration of LEuH, which
reveal that the LEuH has low cytotoxic effects on most cells.
Fig. 5 Emission spectra of NO3–LEuH (a), and composites NPX–
LEuH-1 : 0.5 (b), NPX–LEuH-1 : 0.7 (c), NPX–LEuH-1 : 1 (d), NPX–
LEuH-1 : 1.2 (e).
3.5 The NPX release of NPX–LEuH nanocomposites
a low deprotonation degree and NPX can transfer energy to
Eu3+ more efficiently in this case.
Fig. 8 shows the UV-vis absorption spectra of NPX–Na in
Na2HPO4–NaH2PO4 buffer solution (pH = 6.86), and the con-
centration of the solution is 2 × 10−5 mol L−1. There exists
three main peaks at 288 nm, 317 nm, and 330 nm, and the
maximum peak appears at 330 nm. So 330 nm is chosen as a
UV detection wavelength to measure the standard curve, and
the standard curve equation is shown as follows:
3.4 The HPLC method validation and the cytotoxic effect
Fig. 6 shows the typical HPLC chromatograms of NPX. Under
the conditions of detection, the retention time for NPX is
approximately 4.4 min. The chromatographic peak of NPX in
the standard sample exhibited a sharp and symmetrical profile
(Fig. 6A). A similar peak is observed in the chromatogram
Conc ðmol Lꢁ1Þ ¼ 7:01 ꢀ 10ꢁ6 Abs þ 2:07 ꢀ 10ꢁ7
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Fig. 7 Cytotoxic effect of NO3–LEuH on different cells based on a cell
survival assay. (A) Brain glioma U87MG cells. (B) Breast cancer
MDA-MB-435S cells. (C) Murine brain microvascular endothelial cells
(BMVECs). (D) Human umbilical vein endothelial cells (HUVECs).
Fig. 9 (A) The standard curve of concentration–absorbance of NPX–Na
in Na2HPO4–NaH2PO4 buffer solution (pH = 6.86). (B) Release kinetics
of NPX from the NPX–LEuH-1 : 0.5 nanocomposite at pH 6.86 and
37 °C.
4. Conclusions
In summary, the drug naproxen (NPX) is intercalated into
layered europium hydroxide (LEuH) to form nanocomposites.
Different deprotonation degrees lead to NPX–LEuH composites
with diverse structures (horizontal and vertical arrangements),
and the TG-DTA results indicate an elevated thermal stability
of organic species after intercalation. Photoluminescence
investigation shows that the Eu3+ luminescence is markedly
enhanced for the NPX–LEuH-1 : 0.5 and the composites with
more complete deprotonation (NPX–LEuH-1 : 0.7/1 : 1/1 : 1.2)
Fig. 8 UV-vis absorption spectra of NPX–Na in Na2HPO4–NaH2PO4
buffer solution (pH = 6.86), the concentration of the solutions is 2 ×
10−5 mol L−1
.
where the Conc and Abs is the concentration and absorbance show a slight luminescence enhancement. This may be
of the NPX–Na solution, respectively. ascribed to the well matching of the triplet energy level
As is shown in the release profile of NPX from NPX– between NPX and Eu3+ for the NPX–LEuH-1 : 0.5 composite
LEuH-1 : 0.5 at pH 6.86 and 37 °C (Fig. 9), the NPX–LEuH and NPX can transfer energy to Eu3+ more efficiently in this
nanocomposite can control the release of NPX. The contact case. The content of naproxen in the intercalation material
time needed for 91% of the maximum NPX-release amount is can be confirmed by HPLC. The cytotoxic effect of LEuH is
135 min, and the complete release needs about 200 min. The observed with a sulforhodamine B (SRB) colorimetric assay,
release mechanism can be ascribed to the ion-exchange reac- which reveals that the LEuH has low cytotoxic effects on most
−
tion between NPX and HPO42−/H2PO4 in bulk solution. The cells. The drug release behavior is studied in detail in
ion-exchange velocity is fast at the beginning and slows down Na2HPO4–NaH2PO4 buffer solution (pH 6.86 and 37 °C). The
gradually with the exchange reaction. The experimental results NPX–LEuH composites can control the release of NPX and the
indicate that the NPX–LEuH nanocomposite is indeed a poten- complete release needs about 200 min. The release mecha-
tial drug delivery system, which may be attributed to the nism can be ascribed to the ion-exchange reaction between NPX
−
restricted motion of NPX anions arising from the steric effect and HPO42−/H2PO4 in bulk solution. The fabrication of LRH
of LRHs and the electrostatic interaction between NPX anions nanocomposites with drug molecules shows a novel method to
and positively charged LRH layers.
prepare a nano-drug delivery system based on LRHs integrating
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Acknowledgements
This work is supported by the Undergraduates Research Train-
ing Program (URT: 2016J00103) of Beijing Municipal Edu-
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Notes and references
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