Applied Surface Science 287 (2013) 5461

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Applied Surface Science

journal homepage: www.elsevier.com/locate/apsusc

Alkali activation of halloysite for adsorption and release of ooxacin

Qin Wang, Junping Zhang , Aiqin Wang
Center of Eco-material and Green Chemistry, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, PR China

a r t i c l e

i n f o

Article history:
Received 21 June 2013
Received in revised form 4 September 2013
Accepted 10 September 2013
Available online 17 September 2013
Keywords:
Halloysite
Alkali activation
Adsorption
Controlled release
Ooxacin

a b s t r a c t
Halloysite nanotubes are promising vehicles for the controlled release of drug molecules. Here, we systematically investigated the effects of alkali activation on the physicochemical properties, structure and
morphology of halloysite nanotubes by XRD, FTIR, SEM and TEM, etc. Afterwards, the adsorption and
in vitro release properties of halloysite for cationic ooxacin (OFL) were evaluated. The results indicate
that alkali activation dissolves amorphous aluminosilicate, free silica and alumina, which results in the
increase in pore volume and pore size. OFL is adsorbed onto halloysite via electrostatic interaction and
complexation. Alkali activation could increase the adsorption capacity of halloysite for OFL and prolong
release of the adsorbed OFL compared with the natural halloysite. Thus, alkali activation of halloysite is
an effective protocol to improve the adsorption and prolong release for cationic drug molecules.
2013 Elsevier B.V. All rights reserved.

1. Introduction
Recently, some clay minerals, e.g., montmorillonite, hydrotalcite and laponite, are used in pharmaceutical technology as ideal
excipients and substances with suitable biological activity due to
their excellent properties including chemical inertness, good biocompatibility, high specic surfaces areas, large pore volumes, and
mechanical stability [1,2]. Halloysite (Al2 (OH)4 Si2 O5 2H2 O) is a
tubular clay mineral. The external surface of halloysite is composed
of siloxane (SiOSi) groups and the internal surface consists of
a gibbsite-like array of aluminol (AlOH) groups. The difference
in composition of external and internal surfaces results in a negatively charged external surface and a positively charged inner
lumen in pH 28 aqueous solutions [35]. Halloysite nanotubes
are important nano-vehicles for encapsulation of many biologically
and chemically active substances due to the nano-tubular structure and good biocompatibility [68]. Many drug molecules such
as proteins, resveratrol [9], tetracycline hydrochloride [10] and
doxorubicin [11] have been loaded onto halloysite. However, the
adsorption capacity of natural halloysite for drug is often low. For
example, the adsorption capacity of halloysite for 5-aminosalicylic
acid is only about 4.00 mg/g [12].
Many literatures have reported that an increase in the lumen
diameter of halloysite or modication of halloysite with polymers
can improve adsorption capacity of halloysite for drug molecules
[13,14]. For instance, H2 SO4 activation at certain temperature can

Corresponding author. Tel.: +86 931 4968251.

E-mail address: jpzhang@licp.cas.cn (J. Zhang).
0169-4332/$ see front matter 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.apsusc.2013.09.057

enlarge the lumen of halloysite nanotube, and the loading efciency

for benzotriazole increased 4 times after removal of 60% of alumina
compared with natural halloysite [15]. However, we found that
HCl activation at room temperature cannot increase the adsorption
capacity of halloysite for drug although the increases in both BET
and pore volume of halloysite were detected owing to removal of
a part of alumina. Besides acid activation, alkali activation also can
increase the lumen of halloysite nanotube by dissolving amorphous
aluminosilicate, free silica, and free alumina [16,17]. However, little
information can be seen concerning the effects of alkali activation of
halloysite on its adsorption capacity and release property for drug
molecules.
Here, we report the effects of alkali activation on the physicochemical properties of halloysite, the adsorption mechanism and
release kinetics for ooxacin (OFL) on the basis of our previous work
about clay minerals [18,19] and controlled drug release [20,21].
OFL, one of a new generation of uorinated quinolones [22], was
used as the model drug. It was found that alkali activation could
improve the adsorption capacity of halloysite for OFL and prolong
its release.

2. Materials and methods

2.1. Materials
Halloysite clay was purchased from Sigma-Aldrich. OFL was supplied by Kunshan Double-crane Pharmaceutical Co., Ltd (Jiangsu,
China). Other agents used were all of analytical grade and all solutions were prepared with distilled water.

Q. Wang et al. / Applied Surface Science 287 (2013) 5461

2.2. Alkali activation of halloysite

The alkali-activated halloysite samples were obtained according to the following procedure. 4.0 g of natural halloysite powder
was suspended in 40 mL of NaOH solution of various concentrations
(0.5, 4 and 6 mol/L). The mixture was sonicated at 50 C for 1 h, and
then washed with distilled water for many times until neutrality.
The resulting sample was dried at 105 C to constant weight and
ground to a size of 200-mesh.
2.3. OFL adsorption
An amount of 0.1 g OFL was dissolved in 50 mL of pH 3.00 acetic
acid solution, and then 1.0 g of halloysite sample was added. The
mixture was shaken in a thermostatic shaker bath (THZ-98A) at
150 rpm and 35 C for 24 h to reach adsorption equilibrium. Afterwards, the suspension was centrifuged at 4500 rpm for 10 min and
the solid was dried to a constant weight in an oven at 105 C. The
pH of solutions was measured using a Mettler Toledo 320 pH-meter
during the adsorption process.
To evaluate the adsorption capacity of halloysite for OFL, an
indirect method was used. The supernatant after adsorption were
diluted to 200 mL with distilled water. The concentration of OFL
was determined using a UVvis spectrophotometer (SPECORD 200,
ANALYTIK JENA AG) at 293 nm. The adsorption capacity (mg/g) was
calculated using the following equation.
Adsorption capacity(mg/g) = (w c v)/m

(1)

where w is the mass of OFL used for drug loading, mg; c is the
concentration of OFL in the ltrate, mg/mL; v is the volume of the
ltrate, mL; m is the mass of halloysite used for drug loading, g.
2.4. Determination of Al(III)
The concentrations of Al(III) in the supernatant as mentioned
in the above section were determined using Duo View ICP-OES
spectrometer (iCAP 6300MFC, Thermo Fisher Scientic, UK). For
comparison, the leaching of Al(III) from halloysite samples in pH
3.0 acetic acid solution was also studied. The only difference is no
OFL was added.
2.5. In vitro release studies
In vitro release experiments were carried out using an intelligent
dissolution apparatus by immersing 0.25 g of the OFL-loaded halloysite samples in 500 mL of pH 1.20 solution (simulated gastric
uid). The mixture was stirred at 50 rpm and 37 1 C. At predetermined time intervals, 5 mL of the solution was taken and the
same amount of the fresh dissolution media was added back to
maintain a constant volume. The collected 5 mL of the solution was
ltrated through a membrane with a pore diameter of 0.45 m.
The ltrate (3 mL) was diluted to 10 mL with the fresh dissolution media. The concentration of OFL was determined by a UVvis
spectrophotometer at 293 nm, and then the cumulative release percentage of OFL was obtained. The cumulative release results are the
average of three measurements.
2.6. Characterization
FTIR spectra of samples were recorded on a Thermo Nicolet NEXUS TM spectrophotometer using a KBr pellet. The
morphology and microscopic structures of the samples were
observed using FE-SEM (JSM-6701F, JEOL, Ltd.) and TEM (TECNAIG2-F30, FEI). The specic surface area of the samples was
determined by the BrunauerEmmettTeller (BET) method. The
pore volume and pore-size distribution were estimated by the

55

BarrettJoynerHalenda (BJH) method at 77 K (ASAP 2020 M,

Micromeritics Instrument Corporation). Power XRD analysis was
performed using a diffractometer with Cu anode (PAN alytical
Xpert PRO), running at 40 kV and 30 mA, scanning from 3 to 70
at 3 /min. The zeta potentials of the samples were measured using
Zetasizer Nano ZS (Malvern Instruments Ltd., Worcestershire, UK)
by dispersing 0.1 g of the sample in 10 mL of pH 3.00 acetic buffer
solution. The polydispersity index of halloysite samples was determined by the dynamical mode (dynamic light scattering (DLS)) on
the Light Scattering System BI-200SM, Brookhaven Instruments
device equipped with the BI-200SM goniometer, the BI-9000AT
correlator, temperature controller and the Coherent INOVA 70
C argon ion laser at 20 C. TGA and DSC analyses were carried
out using a STA 6000 (PerkinElmer Instrument Co., Ltd. USA) to
investigate the thermal stability of the samples over a temperature range of 25 to 800 C at a rate of 10 C/min under nitrogen
atmosphere.
2.7. Statistical analysis
Statistical analysis for the determination of differences in the
adsorption and release characteristics within groups was accomplished using one-way analysis of variance, performed with a
statistical program (Origin 7.0). The data were considered to be
signicantly different at p < 0.05. All data are presented as mean
values with standard error (mean SE).
3. Results and discussion
3.1. Morphology analysis
The inuence of NaOH activation on the morphology of halloysite was observed by FE-SEM and TEM (Figs. 1 and 2). As can
be seen from Fig. 1, the natural halloysite is composed of a lot of
nanotubes and a small amount of agglomerates. The length of the
halloysite nanotubes is in a wide range of 0.05 to 1.50 m. After
alkali activation, the stacking degree of the nanotubes decreases
(Fig. 1bd), which indicates that NaOH activation can effectively
disaggregate bundles of halloysite. The TEM image of natural
halloysite (Fig. 2a) is consistent with the SEM observation. The
halloysite has a transparent central area that runs longitudinally
along the cylinder (Fig. 2b, red arrows), indicating that the natural halloysite are hollow and open-ended. The external diameter
of the nanotubes varies from 20 to 100 nm and their internal
diameter ranges from 5 to 30 nm (Fig. 2c). After alkali activation,
some nanoparticles and nanosheets aggregate outside the nanotubes (Fig. 2d, red rectangle), which should originate from the
collapsed fragile nanotubes. Similar morphology was observed by
treating halloysite with 1.0 mol/L NaOH according to White et al.
[17].
3.2. XRD analysis
The XRD patterns of natural and alkali-activated halloysite samples were shown in Fig. 3. The natural halloysite shows a sharp
which is ascribed to halloysite-(7 A).
Furpeak at 12.0 (d = 7.35 A),
ther conrmation of the dehydrated state is the presence of the
and the 0 2 0/1 1 0 basal
0 0 2 basal reection at 24.9 (d = 3.58 A)
The characteristic peaks of quartz
reection at 20.33 (d = 4.37 A).
and alumite (KAl3 (SO4 )2 (OH)6 , d = 2.98 A)
also can
(SiO2 , d = 3.34 A)
be seen [23]. Alkali activation with a NaOH concentration of less
than 4.0 mol/L has no inuence on position of the typical diffraction
peaks of halloysite. However, the typical diffraction peak (0 0 1) of
halloysite shifts slightly from 12.04 to 12.18 and the basal space
correspondingly shifts from 7.35 to 7.27 A when NaOH concentra
tion is 6.0 mol/L. In addition, the reection peak at 19.9 (d = 4.46 A)

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Q. Wang et al. / Applied Surface Science 287 (2013) 5461

Fig. 1. FE-SEM images of (a) 0 (natural halloysite), (b) 0.5, (c) 4.0 and (d) 6.0 mol/L NaOH solution treated halloysite.

ascribed to another characteristic peak of tubular halloysite disappears, indicating etching of alumina [15]. Moreover, the intensity of
the characteristic peak of alumite (KAl3 (SO4 )2 (OH)6 ) at 29.9 gradually decreases with increasing NaOH concentration. The results
suggest that the crystal structure of halloysite has been partly
changes after treated with 6.0 mol/L NaOH solution.

3.3. FTIR analysis

The FTIR spectra of natural and alkali-activated halloysite samples were shown in Fig. 4. In the spectrum of natural halloysite
(Fig. 4a), the absorption bands at 3693 and 3621 cm1 are ascribed
to OH stretching of the inner surface [24], while the band at

Fig. 2. TEM images of (a) natural halloysite (5000), (b) natural halloysite (29,500), (c) natural halloysite (75,000), (d) 0.5 mol/L NaOH solution treated halloysite (12,000).
(For interpretation of the references to color in this gure legend, the reader is referred to the web version of this article.)

Q. Wang et al. / Applied Surface Science 287 (2013) 5461

57

Fig. 5. TG curves of natural and alkali-treated halloysite samples.

Fig. 3. XRD patterns of (a) 0 (natural halloysite), (b) 0.5, (c) 4.0 and (d) 6.0 mol/L
NaOH solution treated halloysite. H: halloysite; Q: quartz; A: alumina.

911 cm1 is ascribed to the bending vibration of the inner OH. The
broad band at 1638 cm1 in Fig. 4a is owing to bending vibration
of adsorbed water. The band at 1114 cm1 is assigned to the apical SiO and that at 1030 cm1 to perpendicular SiO stretching
vibration. The band at 536 cm1 is due to SiO bending mode and
that at 469 cm1 to AlO stretching mode [25]. After treated with
NaOH solution, these intensities of the absorption bands at 3693,
3621 and 911 cm1 decrease with increasing NaOH concentration
(Fig. 4bd), indicating the gradual removal of alumina layers [15],
which is consistent with the XRD results. The peaks of SiOH vibrations at 3525 and 3450 cm1 also gradually disappear. In addition,
decreases in intensities of the peaks at 1030, 536 and 469 cm1
was observed. The FTIR results indicate that alkali-activation could
remove some SiOH and AlOH groups from halloysite.
3.4. Thermal analysis
The decomposition process of the halloysite samples is composed of three main steps according to the TGA and DSC curves
(Figs. 5 and 6) [26]. (i) The rst evident weight loss in TGA curves at
around 91 C is attributed to the dehydration of physisorbed water
and interlayer water. (ii) The second evident weight loss at about
297 C is attributed to the structural decomposition of alunite.
However, this endothermic peak disappears for halloysite treated
by 6 mol/L NaOH solution. This result further proves that alunite
is removed during alkali activation. (iii) The third evident weight
loss appears at 542 C owing to the dehydroxylation of structural
water. The weight loss of halloysite decreases with increasing NaOH

Fig. 6. DSC curves of natural and alkali-treated halloysite samples.

concentration. This means the structural hydroxyl groups in AlO6

octahedral layer are removed along with the dissolving of Al(III)
during alkali activation.
The corresponding DSC curves of natural halloysite and alkaliactivated products are consistent with the TGA results. The maximum endothermic peaks appear at 297 and 542 C, respectively.
All samples are at endothermic status during the whole heating
process owing to the continuous dehydration and dehydroxylation.
3.5. N2 isotherms and pore size distribution
The effect of NaOH concentration on the pore characteristics
of halloysite was investigated by nitrogen sorption. Figs. 7 and 8
show the nitrogen adsorptiondesorption isotherms and the pore

Fig. 4. FTIR spectra of (a) 0 (natural halloysite), (b) 0.5, (c) 4.0 and (d) 6.0 mol/L NaOH solution treated halloysite.

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Q. Wang et al. / Applied Surface Science 287 (2013) 5461

Table 1
Variation of BET surface area, pore volume and average pore size of halloysite samples with NaOH concentration.

Fig. 7. Nitrogen adsorptiondesorption isotherms of natural and alkali-activated

halloysite samples.

Fig. 8. Pore size distribution of natural and alkali-treated halloysite samples.

size distribution of natural and alkali-treated halloysite samples,

respectively. The isotherms of natural and alkali-activated halloysite at 77 K are similar and belong to the type II with H3
hysteresis loops according to IUPAC classication [14]. The appearance of a very narrow hysteresis loops at relative pressure higher
than p/p0 = 0.4 indicates that halloysite samples have broad pore
size distribution, many meso- and macropores. In addition, an
increase in the amount of adsorbed N2 was observed after treated
with NaOH in the range of relative pressure investigated. For example, the amount of adsorbed N2 is 0.29 mmol/g for natural halloysite
at p/p0 = 0.10, whereas it is 0.33, 0.35 and 0.39 mmol/g after activated with 0.5, 4.0 and 6.0 mol/L NaOH, respectively. The amount
of adsorbed N2 increases by 0.1 mmol/g when 6.0 mol/L NaOH is
used. These data indicate that NaOH activation has little inuence
on the number of micropores of halloysite when p/p0 < 0.10. These
results are in accordance with a previous report by White et al. [17].
When p/p0 =0.99, the amount of adsorbed N2 is 4.46, 4.77, 5.50 and
6.17 mmol/g after activated with 0, 0.5, 4.0 and 6.0 mol/L NaOH

NaOH concentration (mol/L)

0.5

4.0

6.0

BET surface area (m2 /g)

Pore volume (cm3 /g)
Average pore size (nm)

32.76
0.088
10.71

33.82
0.096
11.32

34.77
0.101
11.60

39.21
0.120
12.24

solution, respectively. In contrast to the small inuence of alkali

concentration on the amount of adsorbed N2 when p/p0 < 0.10,
about 8.0% of absorbed N2 is attributed to the newly generated
micropores, and more than 40% of absorbed N2 is attributed to
the newly generated meso- and macropores. This result indicates
that NaOH activation generates a larger proportion of meso- and
macropores which can also be observed in Fig. 8.
As can be seen from Fig. 8, there are two peaks at 13 nm corresponding to lumen of the nanotubes and 60 nm attributed to
the pores between close-packed nanotubes [27,28]. The intensities
of these two peaks increase with increasing NaOH concentration,
indicating evident increase in pore volume. Moreover, the pore size
of natural halloysite varied from 1.8 to 114 nm, which includes
pores inside the nanotubes (hollow lumen of nanotubes) as well
as randomly arranged pores outside the nanotubes formed by their
agglomeration into bundles [17]. Whereas the pore size of alkaliactivated halloysite is in the range of 1.8 to 124 nm, 1.8 to 133 nm,
and 1.8 to 132 nm after treated with 0.5, 4.0 and 6.0 mol/L NaOH
solution, respectively.
NaOH concentration also has great inuences on the specic
surface area and pore volume of halloysite as summarized in
Table 1. The BET surface area and pore volume of the alkalitreated halloysite samples are apparently higher than those of the
natural halloysite (32.76 m2 /g and 0.088 cm3 /g). The BET surface
area increases to 39.21 m2 /g and the pore volume increases to
0.120 cm3 /g with increasing the NaOH concentration to 6.0 mol/L.
Similar tendency of average pore size was also observed, which is
in accordance with the SEM observation. This may be due to dissolution of a large quantity of alunite and free alumina and silica
from halloysite during alkali activation.
3.6. OFL adsorption
The colloidal stability of halloysite before and after loading of
OFL was investigated by the dynamic light scattering experiments.
The polydispersity index of the halloysite suspension is 0.358,
whereas the polydispersity index is 2.603 after loading of OFL.
This result indicates that the halloysite nanotubes become easier
to aggregate after loading of OFL [29].
The adsorption capacity of halloysite for OFL was presented in
Table 2. The adsorption capacity increases with increasing NaOH
concentration, and there are signicant differences for all samples
(p < 0.05).
The outer surface of halloysite nanotube is weakly negatively
charged and its inner wall is positively charged. The structure of
halloysite at the edge is disrupted and the surface groups can be

Table 2
Adsorption capacities for OFL in pH 3.0 solution, zeta potential, and pH of original and nal solutions of natural and alkali-activated halloysite samples.
NaOH concentration (mol/L)

Adsorption capacity (mg/g)

0
0.5
4.0
6.0
OFL
OFL-loaded activated halloysite (4 mol/L NaOH)

44.70 0.57
55.26 0.44
59.17 0.65
62.77 0.49

a
b

Zeta potential (mV)

13.62
10.16
8.31
7.35
9.36
7.48

Initial pHa

Final pHb

4.56
4.57
4.56
4.57

5.43
6.29
6.57
6.63

0.1 g OFL was dissolved in 50 mL of pH 3.0 dilute acetic acid solution and no halloysite was added.
0.1 g OFL was dissolved in 50 mL of pH 3.0 dilute acetic acid solution, and 1.0 g of halloysite was added, and then the OFL-loaded halloysite was removed from the solution.

Q. Wang et al. / Applied Surface Science 287 (2013) 5461

59

Fig. 9. The concentration of Al(III) in the supernatant of natural and alkali-treated

halloysite samples in the presence and the absence of OFL.

protonated or deprotonated. So, halloysite may be positively or

negatively charged depending on pH [30]. Table 2 listed the zeta
potentials of natural and alkali-treated halloysite and OFL in pH 3.0
solution. It can be seen that the zeta potentials of natural and alkalitreated halloysite at pH 3.0 are 13.62, 10.16, 8.31 and 7.35 mV
after activation with 0, 0.5, 4.0 and 6.0 mol/L NaOH solution, respectively, whereas that of OFL is 9.36 mV. These results indicate that
there is a electrostatic interaction between halloysite samples and
OFL, which may result in a higher adsorption capacity. After alkali
activation, the zeta potential increases gradually by increasing
NaOH concentration, which will theoretically lead to decrease of
adsorption capacity. Whereas the fact is the adsorption capacity
increases with increasing NaOH concentration. This means there
should be some other important mechanisms for the adsorption of
OFL onto alkali-treated halloysite besides electrostatic interaction.
In addition, the zeta potential of OFL-loaded activated halloysite
(4.0 mol/L NaOH) is 7.48 mV (Table 2). This result indicated that
the surface of halloysite nanotubes is positively charged due to the
surface adsorption of OFL.
Generally speaking, the adsorption of halloysite for OFL is also
related to its pore property. The adsorption capacity of alkalitreated halloysite for OFL and BET surface area, pore size and pore
volume of alkali-treated halloysite show similar tendency with
increasing NaOH concentration (Tables 1 and 2). This indicates that
the increase of BET surface area, pore size and pore volume may be
responsible for the increase of adsorption capacity.
It is well known that pharmaceutical compounds with
carboxylic and phenolic groups, such as tetracycline and uoroquinolone, could form strong complexes with metal cations.
Moreover, a similar reaction could occur in the presence of hydrous
oxide minerals [31,32]. Therefore, ketone group (C=O) and carbonyl
groups (COOH) of OFL may form stable complexes with the hydrous
oxides of Al(III) and other metal ions on the surface of halloysite.
To prove the complexation mechanism of alkali-treated halloysite
with OFL, the concentration of Al(III) in the supernatants was
determined via iCAP (Fig. 9). For comparison, the concentration
of Al(III) in the absence of OFL was also studied. As can be seen,
the concentration of Al(III) in the presence of OFL is obviously
higher than that in the absence of OFL. This implies that OFL could
induce the dissolution of Al(III) from halloysite by forming stable
complexes. The ligand-promoted dissolution evidently increases
the concentration of Al(III) in the supernatant. Moreover, the concentration of Al(III) increases with increasing alkali concentration,
which means a higher alkali concentration facilitate the complexes
to remain in the supernatant. Besides the OFLAl(III) complexes
in the supernatant, a part of OFLAl(III) complexes remain in
the halloysite nanotubes. This could be proved in terms of the
change of the pore volume attributed to the lumen of the halloysite
nanotube before and after adsorption as shown in Fig. 10. The inner

Fig. 10. Pore size distribution of halloysite sample treated with 0.5 mol/L NaOH
solution before and after OFL adsorption.

wall of halloysite nanotube is positively charge because its internal

surface consists of gibbsite octahedral sheet (AlOH) groups
according to Guimares et al. [5]. So, there is no electrostatic interaction between positive OFL and positive inner wall of halloysite.
However, it can be seen in Fig. 10 that the pore volume decreases
after adsorbing OFL. This indicates that OFL forms complexes with
amorphous Al(III) in the lumen of halloysite nanotube, which
remains in the lumen and results in the decrease of pore volume.
Therefore, the complexation between C=O and COOH groups of
OFL and amorphous Al(III) in the lumen of halloysite is another
important adsorption mechanism besides electrostatic interaction.
Similarly, the concentration of Al(III) also increases with increasing NaOH concentration in the absence of OFL. Then, here comes
a question. Why a higher Al(III) concentration was detected in
the supernatant for alkali-treated halloysite in the absence of OFL
with increasing NaOH concentration since alumite dissolves in
the course of alkali activation? The possible explanation is that
Al(III) dissolved from halloysite nanotubes reacts with OH ions in
alkaline solution to form Al(OH)3 nanosheets [17]. Subsequently,
the Al(OH)3 nanosheets attach back onto the surface of halloysite
during alkali activation and ltration. When alkali-treated halloysite samples disperse in pH 3.0 acetic acid solution, the Al(OH)3
nanosheets dissolve and dissociate Al3+ ions, which could increase
the Al(III) concentration in the supernatant. Thus, a higher Al(III)
concentration was detected in the supernatant with increasing
NaOH concentration.
3.7. In vitro release of OFL
In vitro release behavior of OFL from alkali-treated halloysite at
pH 1.2 and 7.4 were shown in Fig. 11. As can be seen in Fig. 11(a),
NaOH concentration has great inuences on the cumulative release
of OFL. The cumulative release of OFL from natural halloysite is
about 61% after 12 h and 76% after 24 h. After treated with 0.5 mol/L
NaOH, an evident decrease in the cumulative release to 60% after
24 h was observed. Further increase in NaOH concentration results
in a further decrease in the cumulative release, but the cumulative release of OFL from the 6.0 mol/L NaOH treated halloysite
is slight higher than that from the 4.0 mol/L NaOH treated. In
addition, pH has an inuence on the release of OFL. The release
of OFL becomes slower with increasing pH to 7.4 because of lower
solubility of OFL in pH 7.4 [33]. Moreover, the cumulative release
rate of OFL in Fig. 11(b) is in the order of NaOH-0 mol/L > NaOH0.5 mol/L > NaOH-6.0 mol/L > NaOH-4.0 mol/L, which is consistent
with that at pH 1.2.

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Q. Wang et al. / Applied Surface Science 287 (2013) 5461

activation at room temperature has no obvious effect on the crystal structure of halloysite when the NaOH concentration is less
than 4.0 mol/L. Both BET and pore volume of halloysite increase
with increasing NaOH concentration. OFL is adsorbed onto halloysite via electrostatic interaction between protonated OFL and
negative halloysite surface, and the complexation between OFL and
amorphous Al(III) in the lumen of halloysite nanotube. Increases in
both BET and pore volume of halloysite improve the OFL adsorption
capacity though the ligand-promoted dissolution could result in the
decrease of adsorption capacity of halloysite for OFL. OFL also enters
into the lumen of halloysite besides the external surface adsorption.
Alkali activation can prolong the release of the adsorbed OFL and
is proved to be an effective approach to improve adsorption and
release for cationic drugs.
Acknowledgments
The authors are thankful for the joint supports of the National
Youth Natural Science Foundation of China (No. 51003112) and
the Special Research Fund of Scholarship of Dean of CAS.
References

Fig. 11. In vitro release of OFL from natural and alkali-activated halloysite samples
(a) pH 1.2 and (b) pH 7.4.
Table 3
The kinetic constants (k), diffusional exponents (n), and correlative coefcients (r2 )
following linear regression of release data of natural and alkali-treated halloysite at
pH 1.2 and 7.4 media.
NaOH concentration
(mol/L)

0
0.5
4.0
6.0

pH 1.2

pH 7.4

n1

k1

r1 2

n2

k2

r2 2

0.235
0.240
0.251
0.194

34.43
28.12
17.86
22.91

0.977
0.947
0.969
0.960

0.306
0.337
0.341
0.297

24.27
19.05
15.28
18.32

0.975
0.972
0.957
0.974

To elucidate the kinetics of OFL release, the experimental data

was analyzed using the Power law (Mt /M = ktn ) [34,35]. According to Siepmann and Peppass report, for cylinder, an n value of
0.45 indicates the drug release mechanism approaches to a Fickian diffusion controlled release, whereas n equal to 0.89 indicates
the drug release mechanism approaches to Case-II transport. The n
value from 0.45 to 0.89 is a drug release mechanism for anomalous
transport. From the logarithmic plot of release data log (Mt /M )
versus log t, the diffusion exponent (n) and kinetic constant (k)
have been calculated and the values for the halloysite in pH 1.2
and 7.4 medium are listed in Table 3. The n value is in the range of
0.194 to 0.251 at pH 1.2 and 0.297 to 0.337 at pH 7.4. The n value
increases and then decreases with increasing NaOH concentration.
It is believed that the OFL release mechanism is Fickian diffusion,
and can be controlled by the interactions (such as electrostatic
interaction and complexation) between OFL and halloysite.
4. Conclusions
This study revealed the inuences of alkali activation on crystal structure, morphology and pore information of halloysite. Alkali

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