J Sol-Gel Sci Technol (2014) 69:364–369
DOI 10.1007/s10971-013-3228-x
ORIGINAL PAPER
Synthesis of pH-responsive mesoporous silica nanotubes
for controlled release
Jie Ma • Huiming Lin • Rong Xing •
Xiaofeng Li • Chunhui Bian • Di Xiang •
Wei Guo • Fengyu Qu
Received: 20 August 2013 / Accepted: 27 November 2013 / Published online: 20 December 2013
Ó Springer Science+Business Media New York 2013
Abstract A novel mesoporous silica tubes (MMT) which
possessed pH-sensitive controlled release ability had been
fabricated and synthesized by using carbon nanotubes
(CNTs) as template. The sample replicated the morpholo-
gies of the CNTs successfully. The Brunauer–Emmett–
Teller surface area of the materials can reach 1,017 m2 g-1
with the pore size of 3.8 nm. As a model drug, metformin
HCl was applied to study the drug loading and control
release ability of the materials. MMT possesses higher drug
loading ratio (36 %) than that of MCM-41 (27.5 %). The
release kinetics were studied in simulated gastric fluid
(pH = 1.2) and in simulated proximal intestine fluid
(pH = 7. 4), respectively. The result shows that the
delivery systems exhibit well pH-sensitive control release
ability and the as-synthesized materials have potential
application in biomedical field.
Keywords Mesoporous silica  Carbon nanotubes 
pH-responsive  Controlled release
1 Introduction
As a drug host, mesoporous silica materials, such as,
MCM-41, MCM-48 and SBA-15 etc., are drawn much
attention due to its adjustable pore size, non-toxic nature,
good biocompatibility and so on [1–3]. Early, mesoporous
silica materials were used as the hosts for drug molecules
making the drug release process controlled just by the pore
J. Ma  H. Lin  R. Xing  X. Li  C. Bian  D. Xiang 
W. Guo  F. Qu (&)
College of Chemistry and Chemical Engineering, Harbin Normal
University, Harbin 150025, People’s Republic of China
e-mail: qufengyu2013401@gmail.com
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size and morphology of the host. However, due to the can
not keep drug bioactivity, lower loading ratio, shorter
release time and so on, the ordinary drug release process
can not satisfy the clinical needs [4].
To make sure necessary drug delivery amount and tar-
geted position, the drug controlled release system
responding to the internal or external stimulation (e.g.,
temperature [5], pH [6–9], light [10], magnetism [11, 12]
and luminescence [13–15]) can be adopted. The synthesis
of stimuli-responsive drug controlled release system based
on the functional mesoporous silica materials has been
widely investigated and attracted increasing attention [16,
17]. Huang et al. [18] synthesized magnetic mesoporous
silica spheres with different morphologies and pore sizes
by the S/O/W single-emulsion method,showing the well
targeted drug delivery performance. Meng et al. [19]
reported a novel mesoporous silica delivery system capable
of drug delivery based on the function of—cyclodextrin
nanovalves that are responsive to the endosomal acidifi-
cation conditions in human differentiated myeloid and
squamous carcinoma cell lines. Furthermore, they demon-
strate how to optimize the surface functionalization of the
MSNP so as to provide a platform for the effective and
rapid doxorubicin release to the nuclei of KB-31 cells.
As we know, human body shows various pH environments
in different positions. The pH value of stomach, lintestine,
blood and tumor is about 1.5–2, 7.4, 7.35–7.45 and 5.8–7.2
respectively. Therefore pH-sensitive drug release systems
play an important role in controlled drug delivery systems.
Yang et al. [20] reported an efficient pH-responsive carrier
system has been constructed by oppositely charged ionic
interaction between carboxylic acid modified SBA-15 sil-
ica rods and polyelectrolyte. Xue et al. [21] reported a
poly(D,L-lactide-co-glycolide) (PLGA)/mesoporous silica hybrid
structure (PS hybrid structure),which was synthesized via a
J Sol-Gel Sci Technol (2014) 69:364–369
novel sol–gel route assisted by single emulsion solvent
evaporation.
In this paper, mesoporous silica with tube structure was
synthesized via a facile one-step sol–gel method with
carbon nanotube (CNTs) as the hard template. Eudragit-
S100, a pH sensitive anionic polymer, was coating outside
the mesoporous materials, showing the well pH sensitive
drug release performance. Metformin HCl (MH) was used
as the model drug. The release kinetics of MH from these
ES/HMMT was discussed in simulated gastric fluid (SGF,
pH = 1.2) and simulated proximal intestine fluid (SIF,
pH = 7.4), respectively.
2 Experimental section
2.1 Materials
All the reagents were analytic reagent grade and purchased
from commercial without further purification. Tetraethyl
orthosilicate (TEOS, Tiantai Chemical Co., Tianjin),
Cetyltrimethylammonium bromide (CTAB), carbon nano-
tube (CNTs), polyvinylpyrrolidone (PVP), NH3H2O, eth-
anol (Yongda Chemical Reagent Company, Tianjin),
Metformin HCl (MH, Shandongkeyuan, Jinan), Eudragit-
S100 (Shanghai, China).
2.2 Synthesis of mesoporous silica tube (MMT)
CNTs (0.2 g) were added into of an ethanol (100 mL)
solution including PVP (1.0 g). Then the above solution
was stirring 12 h until it became homogeneous at room
temperature. The mixture was separated by centrifugation
and washed three times with ethanol. The resulting mate-
rial was dissolved in mixing solution of distilled water,
ethanol and ammonia. The solution was continuingly
ultrasound for 40 min for producing CNTs disperse in the
solution perfectly. After the solution turned uniform,
CTAB (0.62 g) was added into above solution. When
CTAB was dissolved completely, TEOS (1.05 g) was
poured into the solution under vigorous stirring. Stirring
was continued for 12 h, and then the resulting solid was
collected by centrifugation and washed three times with
ethanol and dried in and dried in air at ambient temperature
and named CNTs@SiO2. The CNTs@SiO2 was calcined at
550 °C for 6 h to remove the templates. The sample was
named as MMT.
2.3 Drug loading
Typically, MMT sample (0.206 g) was suspended in H2O
(10 mL) solution of MH with a concentration of
0.1 mol L-1. The mixture was stirred for 2 h at room
365
temperature in a sealed vial to prevent the evaporation of
the H2O. The drug-loading MMT powder was recovered by
vacuum filtration and dried at room temperature. 10 mL
filtrate was extracted and properly diluted. And then it was
analyzed by UV–vis spectroscopy at a wavelength of
237 nm, to determine the drug-loading with the differential
method. And thee sample was named as MMT/MH.
The MMT/MH tablets with a diameter of 10 and
0.5 mm in thickness were obtained by pressure on pre-
forming machine at 4 MPa. Then, the EudragitS-100
(5.0 wt%) ethanol solution was dropped on the surface of
MMT/MH tablets and dried in air at room temperature.
When the ethanol outside the tablets volatilized com-
pletely, the pH-sensitive EudragitS-100 was fully coated on
the surface of the MMT/MH tablets named as ES/MMT/
MH.
2.4 Drug release in vitro
Briefly, ES/MMT/MH was immersed in beaker with
300 mL of release media (SGF, pH = 1.2 and SBF,
pH = 7.4) solution. The beaker was incubated at 37 °C in
a thermostat shaker. At appropriate intervals, the release
medium (3.0 mL) was taken and immediately replaced
with an equal volume of fresh. The 3.0 mL extracted
solution was properly diluted to estimate the concentration
of drug release. Finally the MH content was analyzed for at
237 nm using UV–vis spectrometer. Calculation of the
corrected concentration of the released MH is based on the
following equation:
vXt¼1
Ctorr ¼ Ct þ Ct ð1Þ
V 0
where Ctorr is the corrected concentration at time t, Ct is the
apparent concentration at time t, v is the volume of sample
taken, and V is the total volume of the dissolution medium.
2.5 Characterization
The morphologies of the prepared samples were charac-
terized using a scanning electron microscope (SEM, Hit-
achi S4800) at an accelerating voltage of 20 kV. Powder
X-ray diffraction (XRD) data were collected on a Bruker
D8 ADVANCE diffractometer at 40 kV and 30 mA, using
Cu Ka radiation. The specific surface area of samples was
determined using Brunauer–Emmett–Teller (BET) (NOVA
4200E Surface Area and Pore Size Analyzer, Quanta-
chrome, USA). The pore size distributions were calculated
from the adsorption branches of the N2 adsorption iso-
therms using the Barrett–Joyner–Halenda (BJH) model.
Fourier transform infrared (FTIR) spectra were recorded on
a Perkin–Elmer 580B Infrared Spectrophotometer using the
KBr pellet technique. The UV–vis absorbance spectra were
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366
Fig. 1 SEM images of CNTs (a) and HMMT (b)
Intensity
1 2 3 4 5 6
2theta (degree)
Fig. 2 Low-angle XRD of MMT
measured using a Shimadzu UV-3101PC spectroscope.
Transmission electron microscopy (TEM) images were
recorded on a FEITecnai F20 instrument.
3 Results and discussion
3.1 Structural characteristics of samples
The SEM images of CNTs and MMT are exhibited in
Fig. 1. From Fig. 1a, CNTs reveals the typical tube mor-
phology with 50–150 nm in diameter and several microns
in long. From Fig. 1b, MMT also shows the tube structure,
implying the well replication of the hard templates of
CNTs. Figure 2 shows the small angle XRD pattern of
MMT. Just only one diffraction peak at 2h = 2.3 can be
found in Fig. 2, suggesting the mespororous structure with
low ordered degree of the sample.
In order to testify the remove of the hard template
CNTs, wide angle XRD was used. Figure 3 shows the
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J Sol-Gel Sci Technol (2014) 69:364–369
(a): CNTs
(b): CNTs@SiO2
(c): HMMT
Intensity
(c)
(002)
(b)
(a)
20 25 30 35 40
2theta (degree)
Fig. 3 Wide-angle XRD of CNTs (a), CNTs@SiO2 (b), and MMT
(c)
XRD patterns of CNTs, CNTs@SiO2 and MMT. From
Fig. 3, CNTs and CNTs@SiO2 show the diffraction peak at
2h = 26.4°, ascribing to the (002) diffraction of graphite.
After calcination, there is not diffraction peak present for
MMT, implying the remove of CNTs under high temper-
ature treatment.
The TEM images of MMT are exhibited in Fig. 4. It can
be seen that MMT retains the tubes structure about
150–200 nm in size from Fig. 4a. The tube wall and cavity
is about 50–100 and 50 nm, respectively from Fig. 4b.
Furthermore, MMT shows the worm-like mesoporous
structure that is corresponding to the result of XRD. The
cavity of MMT played an important role to increase the
specific surface area of material and drug loading amount.
The N2 adsorption–desorption isotherm and the BJH pore
size distribution curve of sample were shown in Fig. 5. From
Fig. 5a, it exhibits the characteristic type of IV N2 adsorp-
tion/desorption patterns, with well-defined steps at relative
pressures P/P0 of 0.4–0.6, implying the uniform mesoporous
channels. Narrow peak of the samples in the BJH pore size
J Sol-Gel Sci Technol (2014) 69:364–369 367

Fig. 4 Low (a) and high (b) TEM images of MMT

Fig. 5 Nitrogen adsorption– (a) (b)

desorption isotherm (a) and 700
0.4
pore size distribution curve
Volume Adsorbed(cm3/g)

(b) of MMT 600

dV/dlog (D),cm3 /g
0.3
500

400 0.2

300
0.1

200
0.0
100
0.0 0.2 0.4 0.6 0.8 1.0
5 10 15 20 25 30
Relative Pressure(p/p0 )
Pore size (nm)

Table 1 The structure parameters of the MMT

was focused on 3.8 nm. The BET surface area and pore
Sample SBET (m2 g-1) VP (cm3 g-1) D (nm) volume listed in Table 1. BET surface area and pore volume
was 1,017 m2 g-1 and 0.5 cm3 g-1.This decides the MMT
MMT 1,017 0.5 2.6
possesses the high drug loading ratios (36 %).

Fig. 6 SEM image of MMT/MH and ES/MMT/MH

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368 J Sol-Gel Sci Technol (2014) 69:364–369

2.0 80
MMT\MH:pH=7.4

Cumulative Release Rate (Wt%)

70
1.6 Es\MMT\MH:pH=7.4
MH
60
Transmittance

3177
1.2
50
MCM-41\MH:pH=7.4
956 MMT
0.8 40
1097
30
0.4
3190 20
964
Es\MMT\MH:pH=1.2
0.0
MMT/MH 10
1082
0
4000 3000 2000 1000 0 0 10 20 30 40 50 60 70 80
-1
Wave number (cm ) Time/h

Fig. 7 FTIR spectra of MH, MMT and MM/MH Fig. 8 The release curves of MMT\MH, Es\ MMT\MH, MCM-
41\MH in SIF (pH = 7.4) and Es\ MMT\MH in the SGF (pH = 1.2)

80
The SEM images of MMT/MH and ES/MMT/MH were
offered in Fig. 6. The surface of MMT/MH was rough, but Cumulative Release Rate (Wt%) 70

it became smooth when ES coated on their surface, 60

revealing that ES had been coated successfully.
50
The FTIR analysis of MH, MMT and MMT/MH was
provided in the Fig. 7. For MMT, it can be seen the 40
obvious absorption bands at about 3,439, 1,090 and
30
960 cm-1 indexed –OH, Si–O–Si and Si–OH respectively.
Meanwhile, from the FTIR spectrum of MMT/MH, the 20
peak located at about 3,200 cm-1 assigned to the stretching 10
vibrations of –NH group can be detected from MH, con-
firming the successful loading of MH molecules onto the 0
0 2 4 6 8 10 12 14 16 18 20 22 24
MMT. Time/h
The release behavior cure of MH from the MMT\MH,
Es\MMT\MH, MCM-41\MH in SIF (pH = 7.4) and MH Fig. 9 The release curves of Es\ MMT\MH in pH 1.2 in the first 2 h
and pH 7.4 in the other hours
from the SGF (pH = 1.2) at 37 °C is shown in Fig. 8.
From the release curve of MCM-41\MH, the MH release
slowly and the maximum amount is only 50 % at 24 h. But
to the MMT\MH, MH release in simulated SIF appears to no more than 20 % was released. While in SIF, the release
be much faster, which can release 69 % at 1 h and it takes can reach 70 % at 70 h.
12 h to reach the maximum amount 80 %. With tube In order to further investigate the pH-dependent con-
structure, MMT shows the uniform tube walls about 50 nm trolled release of Es\MMT\MH, the release performance in
in thickness. The short path of the drug molecule release SGF at first 2 h and then in SIF was also shown in Fig. 9.
from the pore into outside makes the fast release perfor- From Fig. 9, Es\MMT\MH release about 11 % at the first
mance. However, after the Es grating, the MH release from 2 h in SGF. When the release medium was changed into
Es\MMT\MH deduces to 32 % at 1 h in SIF. And it takes SIF, the release rate and amount were increased remark-
48 h to reach the maximum 70 %. Eudragit-S100 is a ably. Until 24 h, the release can reach 56 % in SIF. The pH
typical anionic polymer exhibiting pH-dependent solubil- sensitivity was caused by structural change of the polymer
ity. It can be insoluble in acid medium and dissolves at pH associated with ionization of the carboxylic functional
values above 7. The pH-dependent controlled release of group at pH value above 7. In clinical application,
Es\MMT\MH was also carried out in SGF (pH = 1.2) as Es\MMT system can protect the drug in stomach acid, and
contrast. From the release curve of Es\MMT\MH in SGF make the drug release in intestinal position. From the
(pH = 1.2), after 1 h the release reach 10 %. With the above, the Es\MMT system shows the potential application
increase to 36 h, the release increase to 19 %. After 70 h, on the treatment of intestinal disease.

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J Sol-Gel Sci Technol (2014) 69:364–369
4 Conclusions
In summary, the mesoporous silica with nanotube structure
was prepared using a facile sol–gel method by one-step.
CNTs were used as the hard template and CTAB as the
mesoporous template. The synthesized sample shows large
BET surface area 1,017 m2 g-1 and high drug loading
amount %. Furthermore, Eudragit-S100, a pH-sensitive
polymer, was grafted outside MMT making the systems
exhibit well pH-sensitive control release ability. Es\MMT
system inhibits the drug release in acid condition, and
makes the freely release in natural and alkali condition.
That is to say, it can protect the drug in stomach acid, and
make the drug release in intestinal position. From the
above, the Es\MMT system can be used on the treatment of
intestinal disease.
Acknowledgments Financial support for this study was provided by
the National Natural Science Foundation of China (21171045,
21101046), Natural Science Foundation of Heilongjiang Province of
China (ZD201214, B201206), Program for Scientific and Techno-
logical Innovation team Construction in Universities of Heilongjiang
province (2011TD010), Research Fund for the Doctoral Program of
Higher Education of China (20102329110002), Pre-research Found
for Technological Development of Harbin Normal University
(12XYG-11), Foundation of Education Department of Heilongjiang
Province, China (12533037).
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