SYNTHESIS OF ORDERED MESOPOROUS SILICA SBA-15 FOR
APLICATIONS ON CONTROLLED DRUG RELEASE
Antonia F. J. Uchoa1, Raimundo R. Almeida1, Vicente. O. S. Neto1,Francisco S. Dias1, Nágila
M. P. S. Ricardo1, Luiz C. G.Vasconcellos1
1
Departament of organic and inorganic chemistry, Federal University of Ceara, Fortaleza (CE), Brazil
E-mail: af.uchoa@bol.com.br
Resumo. Micro and mesoporous silicate particles are considered potencial drug delivery systems because of
their ordered structures, large surface areas and the ease with which they can be chemically modified. Research
on mesoporous materials for biomedical purposes has experienced an outstanding increase durin recents years.
Since MCM-41 was proposed as drug delivery system, sílica-based materials, such as SBA-15 or MCM-48, and
some organic-inorganic hybrids framework have been discussed as drug carriers and controlled-release
systems. The aim of the present work was the use of mesoporous silicate SBA-15 as drug carrier. Quercetin and
troxerrutin were selected as model drugs and loaded onto the unmodified SBA-15. These materials were
characterized by fourier-transform infra-red spectroscopy (FTIR), N2 adsorption/desorption analysis, X-Ray
diffraction (XDR), thermogravimetric analysis (TG/DTG). The present synthesis route effectively reduces the
total synthesis time from days to a few hours, which is much shorter than the conventional SBA-15. The results
showed that the synthesized materials possessed ordered mesoporous structure. The adsorption behavior of
adsorbents for drugs was investigated using high-performance liquid chromatography (HPLC). The
concentration difference have been dicussed in terms of loading troxerutin and controlling its delivery.
Keywords: mesoporous silica, SBA-15, controlled drug delivery, troxerutin
1.
INTRODUCTION
Over the past three decades, there has been rapid growth in the area of drug delivery
which is due to the underlying principle that drug delivery technology can bring both
commercial and therapeutic values to health care products [Kawi, 2005]. Recently, there has
been increase interest in mesoporous silica materials applied as drug carriers in the field of
controlled drug release, to meet the need for prolonged and better control of drug
administration [Vallet-Regi et al, 2001; Wang, 2009; Mihály, 2011]. These mesoporous
materials have attracted many researchers because their properties such as highly ordered
structure, uniform pore size, and high thermal stability. Furthermore, these materials presents
excellent biocompatibility, in vivo biodegradability make them attractive candidates for a
wide range of biomedical purposes [Mihály et. al., 2011; Laniecki, M.,2011; Zhang, L.,
2010]. The size- and shape-controllable pores of mesoporous silicates can store
pharmaceutical drugs and prevent their premature release and degradation before reaching
their designated target [Tamanoi, F. 2011; Tamanoi, F. et al. 2010]. Unfortunately, because
the vast majority of these studies use pure silica as test substances, templates such as ionic
and nonionic surfactants or amphiphilic block copolymers need to be removed from the as
prepared products by calcination [Zhao, D. et al, 2000] or extraction [Grieken, R., 2003] after
defining the wall structure of mesoporous materials, the template removing process takes a lot
of time and energy [Jin, L., 2010]. In general, a typical synthesis of mesoporous silica ordered
involves a two-step process in which the first step involves the self-assembly of silica and
template species at a given reaction temperature under acidic or basic conditions, and the
second one involves the mesostructure expansion and consolidation of siliceous pore walls
usually performed under static conditions at a higher temperature (e.g., at 100 °C) normally
take from several hours to days [Kao, H-M, 2010; Landskron, K.,2009]. Afterward, the
extraction of the templates is carried out by stirring the materials with appropriate solvents
which further takes several hours. Numerous methods have been developed for the synthesis
of mesoporous materials in order to reduce reaction time and temperature to save energy and
cost without affecting the quality of the materials. In this regard, alternatives synthesis
methods of these materials, such as solvent-free synthesis, microwave heating, and
electrochemical methods deserve particular attention [ Ahn, W-S, 2008]. Sonochemical
methods are more and more often used for the synthesis of novel nanomaterials because can
lead a substantial reduction in crystallization time compared with conventional oven heating
when nanomaterials are prepared. The main event in sonochemical synthesis or
sonochemistry is the creation, growth, and collapse of a bubble that is formed in liquid,
known as an acoustic cavitation which creates the high transient temperature and high
pressure of several thousand bars in the solution [Kao, H-M, 2010; Ahn, W-S, 2008]. This
study shows that the sonochemical mediated synthesis of SBA-15 has several advantages: an
easy way to control the temperature and time of the synthesis and significant reduction in the
total synthesis time. By varying the time of the synthesis, the structural properties of the SBA15 materials can be finely tuned. The surface physical and chemical properties of materials
were investigated by FTIR, XRD, N2 adsorption/desorption analysis, and TG/DTG. This work
describes the adsorption of quercetin (β-glicosidase, antioxidant) and troxerrutin (cicatrização
de defeitos endoteliais capilares e proteção do fígado), on the non-modified SBA-15.
2. MATERIALS AND METHODS
MATERIALS
Chemicals used in this study included pluronics P123 (MW: 5800, Aldrich),
(PEO20PPO70PEO20), as structure directing agent.
Tetraethyl orthosilicate [TEOS,
(CH3CH2O)4Si, 98%, Aldrich], was employed as silica precursor. Ethanol (95%),
hydrochloric acid (HCl, 37%), sodium chloride (NaCl). The troxerrutina was kindly supplied
by company Flora Brasil (Fortaleza-Ceará). All the reactants were used as received.
SYNTHESIS OF MESOPOROUS SILICA
The SBA-15 samples were synthesized under acidic conditions using triblock
copolymer Pluronic P123 (EO20PO70EO20, Aldrich) as the template and tetraethylorthosilicate
(TEOS, Aldrich) as a silica source, with addition of KCl, for enhanced stability and ordering.
The synthesis composition was analogous to that reported elsewhere [2]. In a typical
synthesis, 3.2 g of Pluronic P123 and 8,8 g of NaCl was dispersed in 100 mL of 2 mol. L-1
HCl solution at 40°C. This mixture was then subjected to sonication using an ultrasonic
digital, type 450 Digital Sonifier (Branson, Germany), with an adjustable power output
(maximum 200 W at 20 kHz) to obtain a homogeneous solution. Afterwards, 6.82 g of TEOS
was added into the solution. The samples were sonicated immediately at different time (5, 10,
20 30,and 40 min), at 40°C. The while solid product was collected by centifugation, dried at
100 °C for overnight. The extraction of template was carried from the as-synthesized material
by using microwave in a mixture 1:1 acetona/ethanol for few minutes, and this was repeated
tree times. Finally, the material was filtered, and dried at 110 °C. We denoted this material as
SBA-15-UW.
CHARACTERIZATION
X-ray diffractograms were obtained on a PANalytical X’Pert PRO MPD diffactometer
using Co Kradiation (λ = 1,7889 Å) at 45 kV and 40 mA. The data were collected from 0.5
to 5 of 2θ values with a step size of 0,02°. The unit cell parameter (𝑎ℎ𝑒𝑥 = 2𝑑100 /√3 ) was
determined from the d100 reflections for SBA-15 type materials. Nitrogen physisorption
measurements were carried out a 77 K using Micromeritics ASAP 2020. The pore size
distributions were calculated from the desorption branch of the isotherms with the BJH
method. Samples were treated at 250 °C for 3h before measurements. The thermogravimetric
measurements were performed with a TA-60WS thermogravimetric analyzer (TA
Instruments) with a heating speed of 10°C/min in nitrogen flow. FTIR spectrum was recorded
in KBr pellets on a FTLA 1200 (Bomem) spectrophotometer.
TROXERRUTIN LOADING
Powdered mesoporous samples were loaded with troxerrutin by soaking them, under
continous magnetic stirring for 96 h at room temperature, into a aqueous solution (40 mg/mL)
of troxerrutin. A 1:1 (by weight) ratio of troxerrutin to solid sample was used. Then the Trox
loaded SBA-15 was separated by filtration and dried under atmosphere. The loading capacity
was calculated by measuring the difference in weight to totally dried solid before and after the
loading.
3. RESULTS AND DISCUSSION
The X-ray diffraction patterns measured for the starting materials are show in Fig. 1.
The SBA-15 material exhibited a good 2D hexagonal as evidenced by the narrow (100)
reflection and the clearly resolved higher order reflections. All materials exhibited only one
broad low-angle reflection, indicative of a lower degree of long-range order. There is no
significant difference in the XRD patterns for the SBA samples synthesized under sonication
with a long period. The cell parameters (table 1) are basically unaltered for different reaction
times. The results show that a short sonication treatment of 10 min is sufficient to obtain
ordered SBA-15 silicas. The unit cell parameter a, which was calculated from the (100)
diffraction peak was 179,63Å and 182, 27Å.
(100)
Intensity [A. U.]
SBA-15-UC-5
SBA-15-UW-10
SBA-15-UC-20
SBA-15-UC-30
SBA-15-UC-40
1
2
3
4
5
2
Fig. 1. XRD patterns of extracted SBA-15 materials with different times of the synthesis (5
min, 10 min, 20 min, 30 min, 40 min). [note: C – calcinated; U – ultrasound; W – microwave)
The nitrogen sorption isotherms of all materials are shown in Fig. 2. All the isotherms are of
Type IV according to the IUPAC classification, with H1 hysteresis loops, characteristic of
mesoporous materials with a cylindrical pore arrangement. The pronounced uptake at relative
pressures around 0,4 P/P0 correspond to capillary condensation in the pores. The sharp
capillary condensation step indicated a relatively narrow pore size distribution 4.9 nm, which
is considerably larger than the 3.5 nm pore size obtained from the conventional synthesized
SBA-15 sample. The surface areas and pore diameters were increased initially with increasing
the reaction time at 40°C. All SBA-15 materials show same type of isotherms.
Table 1. Textural characteristic of the studied mesoporous silica materials
Samples
SBET (m2/g) Vp(cm3/g) Dp (nm)
a0 (nm)
Wall thickness
(nm)
SBA-15-UW-10
415,16
0,568
3,75
17,96
14,21
SBA-15-UC-20
512,18
0,600
4,65
18,27
13.62
SBA-15-UC-30
524,75
0,599
4,21
18,27
14,06
400
300
dV/dD
Volume adsorbed (cm /g STP)
250
300
3
3
Volume adsorbed (cm /g STP)
dV/dD
350
10
20
30
40
50
60
70
80
90
Pore width (nm)
200
150
20
40
250
60
80
100
120
140
Pore width (nm)
200
150
100
0,0
0,2
0,4
0,6
0,8
1,0
100
0,0
0,2
Rel. Pressure (P/P0)
0,4
0,6
0,8
1,0
Rel. Pressure (P/P0)
a
b
400
dV/dD
300
3
Volume adsorbed (cm /g STP)
350
0
20
40
60
250
80
100
120
140
160
Pore Width (nm)
200
150
100
0,0
0,2
0,4
0,6
0,8
1,0
Rel. Pressure (P/P0)
c
Fig. 2. N2 adsorption-desorption isotherms of (a) SBA-15-UW-10, (b) SBA-15-UC-20 and (c)
SBA-15-UC-30. The pore distribution curve for each isotherm is show as inset.
The framework vibrations of calcined and extracted siliceous SBA-15 materials were
analyzed by FT-IR spectroscopy and are presented in Fig. 3. FTIR spectrum of SBA-15 is
characteristic of a pure-silica material, in which the stretching vibration modes of surface
silanol groups at ca. 3700–3200 cm-1 are clearly observed. The width of this band together
with the presence of another broad vibration in the 1650–1600 cm-1 range, ascribed to the
δHOH (H2O) points to the existence of adsorbed water on the material surface. Moreover, in the
1250–1000 cm-1 range, high-intensity bands attributed to νSiO of siloxane groups (Si–O–Si)
are observed. Asymmetric stretching vibrations of Si–O–Si (νSiO) at ca. 1080 cm-1,
symmetric stretching vibrations from Si–O bonds (νSiO) at ca. 800 cm-1 and bending
vibrations from Si–O–Si (δSiOSi) a 460 cm-1 are clearly observed. The presence of free silanol
groups (Si–OH) is evidenced by the presence of a acute signal at 3745 cm-1 (νO–H) together
with a weak band at ca. 980 cm-1 (νSiO).
800
954
SBA-15-UC-20
1635
SBA-15-UW-10
2980
970
806
Transmitance %
800
950
1645
1460
1375
2975
Transmitance %
2879
1730
1641
1463
SBA-15-U-20
SBA-15-U-10
1080
4000
3500
3000
2500
2000
1500
1000
500
4000
3500
3000
2500
2000
1500
1000
500
-1
Wavenumber (cm )
-1
Wavenumber (cm )
a
b
Transmitance %
800
954
2975
1724
1637
SBA-15-UC-30
SBA-15-U-30
4000
3500
3000
2500
2000
1500
1000
500
-1
Wavenumber (cm )
c
Fig. 3. FT-IR spectra of (a) SBA-15-UW-10, (b) SBA-15-UC-20 and (c) SBA-15-UC-30. All
spectra shown before and after extraction of surfactant.
TROXERUTIN RELEASE
The results of the troxerutin release from the SBA-15-UW-10 mesoporous silica are
plotted in Fig.4. The concentration of troxerutin release in SBF at pH 7,4 as a function of
time was determined by HPLC. Evaluated was monitored at 260 nm.
100
% Trox
80
60
40
20
0
0
5
10
15
20
25
30
35
Tempo (h)
100
% Trox
80
60
40
20
0
0,0
0,2
0,4
0,6
0,8
1,0
Tempo (h)
Fig. 4. In vitro release of troxerutin from SBA-15-UW-10
Since in vitro dissolution testing is important for drug development and quality control, it has
been used in this study to investigate the difference in the release rate of model drugs from
SBA-15 samples into SBF medium to evaluated the best formulation. As show in Fig. 4 the
initial release is assigned to the immediate release and dissolution of the drug moiety located
on the surface of disc. These systems exhibit different release rate refers to the amount of drug
incorporated, followed by a rate constant for the subsequent hours. Different types of release
may be related to the interaction between the drug and the mesoporous silica via hydrogen
bonds due to the affinity of the functional groups of molecules Trox and silanol groups on the
sides of the silica.
4. CONCLUSIONS
In summary, was demonstrated that the sonochemical mediate synthesis of mesoporous silica
can reduce the synthesis time from days to few hours. It is an easy way to control the
synthesis conditions, and most importantly the structural properties of the SBA-15 materials
can be finely tuned by varying the synthesis temperature and duration. The kinetics of drug
release troxerutin through the silica matrix used has shown to have a release kinetics efficient
and adequate to its purpose. The adsorption capacity and release behavior of Trox model drug
are found to be highly dependent on the different properties of these drug molecules and
surface properties of SBA-15.
5. ACKNOWLEDGMENT
Financial support by Fundação Cearense de Apoio ao Desenvolvimento Científico de
Tecnológico (FUNCAP).
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