Nanosized carriers for hydrophobic compounds based on mesoporous silica: synthesis and adsorption properties

Article abstract of DOI:10.1007/s11172-019-2562-8

MCM-41 type mesoporous silica particles were obtained using a template method in an alkaline medium and cetyltrimethylammonium bromide as a matrix. The structural and adsorption characteristics of the mesoporous material were studied by dynamic light scattering, scanning electron microscopy, low-temperature adsorption—desorption of nitrogen, IR spectroscopy, and simultaneous thermal analysis. It was shown that the obtained mesoporous material possesses high porosity with the specific pore volume in excess of 1 cm³ g^?1. It was established that the size of silica particles does not exceed 200 nm, which is a value acceptable for the penetration of drugs through cell membranes. The optimal compositions of aqueous dispersions of MCM-41 with minimal sedimentation processes were determined. A drug (indomethacin) was encapsulated into the silica pores using the precipitation method at various temperatures (40 and 60 °C), the quantitative parameters of loading efficiency were calculated. The infl uence of temperature on the encapsulation ability was demonstrated.

Full text of DOI:10.1007/s11172-019-2562-8

Russian Chemical Bulletin, International Edition, Vol. 68, No. 7, pp. 1358—1365, July, 2019
1358
Nanosized carriers for hydrophobic compounds based on mesoporous silica:
synthesis and adsorption properties*
A. R. Ibragimova,a D. R. Gabdrakhmanov,a A. R. Khamatgalimov,a A. F. Saifina,a
A. T. Gubaidullin,a S. R. Egorova,b A. A. Lamberov,b M. P. Danilaev,c and L. Ya. Zakharovaa
aArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences,
8 ul. Akad. Arbuzova, 420088 Kazan, Russian Federation.
E-mail: alsu_i@iopc.ru
bKazan (Volga Region) Federal University,
18 ul. Kremlevskaya, 420008 Kazan, Russian Federation
cA. N. Tupolev Kazan National Research Technical University – KAI,
10 ul. K. Marksa, 420111 Kazan, Russian Federation
MCM-41 type mesoporous silica particles were obtained using a template method in an
alkaline medium and cetyltrimethylammonium bromide as a matrix. The structural and adsorp-
tion characteristics of the mesoporous material were studied by dynamic light scattering, scan-
ning electron microscopy, low-temperature adsorption—desorption of nitrogen, IR spectroscopy,
and simultaneous thermal analysis. It was shown that the obtained mesoporous material
possesses high porosity with the specific pore volume in excess of 1 cm3 g–1. It was established
that the size of silica particles does not exceed 200 nm, which is a value acceptable for the
penetration of drugs through cell membranes. The optimal compositions of aqueous dispersions
of MCM-41 with minimal sedimentation processes were determined. A drug (indomethacin)
was encapsulated into the silica pores using the precipitation method at various temperatures
(40 and 60 C), the quantitative parameters of loading efficiency were calculated. The influence
of temperature on the encapsulation ability was demonstrated.
Key words: template synthesis, MCM-41 type mesoporous silica, indomethacin, adsorption.
Insignificant solubility and low selectivity of drugs are
issues of vital importance in modern medicine and phar-
macology. About 40% of commercially available drugs or
new drugs that pass different stages of trials are practically
insoluble in water.1—6 One of the ways of addressing this
problem is through the use of various carriers, which allow
the drug to be transferred to a more soluble stable form.7
Different approaches are currently used, for example,
compositions based on lipids8 or solid dispersions,9,10 etc.
One of the most promising approaches is adsorption on
a porous carrier (mesoporous material), in particular, on
that based on silica (2 nm  pore diameter (D)  50 nm).11
The possibility of using nanoparticles based on meso-
porous silicon dioxide as a drug delivery system is being
studied. Much attention is being directed toward address-
ing problems related to systemic toxicity.12 There are
published examples of the successful use of mesoporous
silica particles for intravenous drug administration in
rats.13,14 The cytotoxicity of mesoporous silica particles
depends on many factors; among them are the number of
surface silanol groups, which cause hemolysis,15 surface
charge (cytotoxicity decreases on going from negatively
to positively charged particles), as well as the concentra-
tion of empty and drug-loaded nanoparticles.13,16
The problem of biodegradability of mesoporous silica
is also being considered.17 The possibility of biodegrada-
tion of silica nanomaterials over several days was shown.
The factors which make it possible to control the rate of
biodegradation were established. They include porosity,
size, morphology of nanoparticles, the possibility of func-
tionalization of the surface, and alteration of the degrada-
tion medium.18 In a review18 discussing the problem of
removal of drug carriers based on mesoporous silicon,
evidence is presented that silica particles are removed from
the liver, spleen, heart, kidneys, brain, and lungs within
four weeks. The intravenous administration of SiO2
nanoparticles loaded with an acetylcholinesterase reacti-
vator in rats is described.14 It was shown that the drug
penetrates through the blood-brain barrier, whereby 94%
of the particles are removed from the brain within a week
and have no effect on the behavior of the rats.
The possibility of varying the size of pores of meso-
* Dedicated to Academician of the Russian Academy of Sciences
A. I. Konovalov on the occasion of his 85th birthday.
porous silica materials is shown,19—23 their large specific
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1358—1365, July, 2019.
1066-5285/19/6807-1358 © 2019 Springer Science+Business Media, Inc.

Nanosized carriers based on mesoporous silica
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 7, July, 2019
1359
were prepared as follows. A weighed amount of indomethacin
(100 mg) was dissolved in ethanol (3 mL) at 40 С, followed by
the addition of powdered MCM-41 type mesoporous silica
(300 mg) with continuous stirring (550 rpm). The encapsulation
procedure was carried out with continuous stirring for 3 h. After
that, the mixture was filtered, washed with ethanol (40 С), and
dried at room temperature. The preparation of silica particles
containing the encapsulated drug at a temperature of 60 С
(MCM-41@IMC-60) was carried out similarly.
Efficiency of indomethacin encapsulation. The obtained
MCM-41@IMC-40 and MCM-41@IMC-60 samples were
washed on the filter with five portions of ethanol (3 mL each)
and the content of non-encapsulated indomethacin in the col-
lected washings was analyzed by spectrophotometry (a Specord
250 PLUS spectrophotometer (Analytik Jena)), using the known
indomethacin extinction coefficient (4382 L mol–1 cm–1 at
 = 320 nm in ethanol). All measurements were carried out in
a 1 cm pathlength cell. The spectra were recorded in the
200—700 nm wavelength range at 25 С.
surface area and high volume make it possible to obtain
agents with a high content of biologically active substances.
At the same time, the presence of voids in silica prevents
the aggregation of drug molecules and increases its stabil-
ity. Surface silanol groups can be used to design active
sites of various nature on the silica surface. These sites
facilitate the immobilization of drugs, their retention and
release at a rate required for efficient therapeutic action.6,24
However, there are a number of problems requiring
further research. In particular, an increase in the specific
surface and volume of pores could considerably increase
the efficiency of drug encapsulation. It is also necessary
to develop new methods for the encapsulation of drugs
into the pores of silica particles. Among the existing
methods, the most frequently used are the sequential
evaporation of solvents; the melting method, which con-
sists of heating the substance and silica above the melting
point of the drug, and the deposition method.25,26 The
main disadvantage of the first two methods is that they do
not include the removal of drugs adsorbed on the surface
of silica after its loading.27,28 Despite significant prog-
ress in the use of mesoporous silica as a drug carrier, the
efficiency of medicinal agent encapsulation is usually
low,5,28—31 excepting certain cases.5
The quantitative parameters determining encapsulation ef-
ficiency were encapsulation efficiency (Eenc) and loading capac-
ity (Eload), which were calculated using the following equations:
Eenc = [(m0 – munload)/m0]•100%,
(1)
Eload = [(m0 – munload)/mSiO2]•100%,
(2)
where m0 is the initial weight of the loaded drug, g; munload is the
The goal of the present work is to synthesize MCM-41
type mesoporous silica, obtain quantitative characteristics
of the sample, determine the factors affecting its sorption
properties, and investigate the use of the obtained material
for drug delivery. Hydrophobic indomethacin was used as
a model drug.32,33
weight of the drug which did not bind to silica particles, g; mSiO
is the weight of mesoporous silica.
2
Physicochemical characterization of mesoporous material and
dispersions based on it. Experiments on dynamic and electro-
phoretic light scattering were carried out using a Zetasizer Nano
nanoparticle analyzer (Malvern). A gas He—Ne laser (4 mW,
633 nm wavelength) was used as a source of laser radiation. All
measurements were performed at a constant scattering angle
(173). Particle sizes were determined according to the Stokes—
Einstein equation for spherical particles:
Experimental
Hexadecyltrimethylammonium bromide (CTAB, 99%,
Sigma), an aqueous solution of NH4OH (25 wt.%, TatChem-
Product, Russia), tetraethoxysilane (TEOS, 99%, Aldrich),
indomethacin (99%, Aldrich) were used as reactants for the
synthesis of mesoporous silica material. Adsorption and desorption
processes were carried out in ethanol (water content no more than
4%). Water passed through the Milli-Q purification system was used
as a solvent and dispersion medium in the preparation of samples.
Synthesis of MCM-41 type mesoporous silica. The MCM-41
type mesoporous silica was obtained using a template method
described earlier.34,35 The synthesis was carried out at room
temperature (25 С). A weighed amount of CTAB (2 g) was dis-
solved in distilled water (270 mL), followed by the addition of
an aqueous solution of NH4OH (205 mL, 25 wt.%). Then, TEOS
(10 mL) was added dropwise to the resulting solution with con-
tinuous stirring. The reaction mixture was stirred for 10 min and
then thermostated at room temperature for 2 h. The white pre-
cipitate formed was filtered, washed with several portions of
distilled water (5×100 mL), dried in air at room temperature
(25 С) for 6 h. The resulting precipitate was calcined in a muffle
furnace at 550 С for 5 h. The product yield was 45% calculated
based on initial TEOS amount.
D = kT/(6πηR),
(3)
where k is the Boltzmann constant, Т is the absolute temperature,
 is the solvent viscosity, R is the hydrodynamic radius. Before
measurements, all solutions were filtered through Millipore filters
with a pore diameter of 450 nm to remove dust.
X-ray analysis was performed on a D8 Advance X-ray
diffractometer (Bruker) equipped with a Vario attachment
and a Vantec linear coordinate detector. Cu-Kα1 radiation
(λ = 1.54063 Å) monochromatized with a Johansson curved
crystal was used at 40 kV and 40 mA. The powdered samples were
smeared on the single-crystal silicon plate. The samples were
scanned over the 1 2θ50 range with a step of 0.008 and an
acquisition time of 0.1—1 s per point. The data were processed
using the EVA software package.
Porous characteristics of the mesoporous silica sample were
determined by low-temperature adsorption—desorption of nitro-
gen using a Quantachrome Autosorb-iQ multi-purpose analyzer
(Quantachrome Instruments, USA). Adsorption isotherms were
obtained at –196 С after degassing the sample at 500 С to
a residual pressure of 0.013 Pa. The specific surface was de-
termined using a BET model, the nitrogen molecular area
was assumed to be 0.162 nm2, the density of N2 in the normal
Encapsulation of indomethacin. Samples of mesoporous silica
containing encapsulated indomethacin (MCM-41@IMC-40)

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Russ. Chem. Bull., Int. Ed., Vol. 68, No. 7, July, 2019
Ibragimova et al.
liquid state, 0.808 g cm–3. The measurement accuracy was
0.1 m2 g–1 5%. The total pore volume and the mesopore size
distribution was calculated from the desorption curve using the
Barrett—Joyner—Halenda (BJH) model.36 The measurement
accuracy was 5%.
The sedimentation kinetics in aqueous suspensions of MCM-41
was studied using a Specord 250 Plus spectrophotometer
(Analytik Jena), registering the optical density at a fixed wave-
length (λ = 320 nm) for 10 min.
The size and morphology of the porous carrier was determined
by scanning electron microscopy using an EVO 50XVP electron
microscope in combination with an INCA-350 energy dispersive
spectrometer (Carl Zeiss). The spectrometer resolution was
130 eV. The analysis was carried out at an accelerating voltage
of 20 kV and a distance of 8 mm from the flange.
Results and Discussion
Characterization of the sample by scanning electron
microscopy (SEM). Microphotographs obtained by SEM
show that the synthesized MCM-41 is formed by particles
with a diameter of 100—200 nm with a highly developed
surface (Fig. 1).
The content of substances in the MCM-41 mesoporous silica
material was evaluated based on IR spectra, which were re-
corded on a Vector 22 Fourier-transform IR spectrometer
(Bruker). Samples were finely ground using KBr granules, the
spectra were recorded in the 4000—400 cm–1 frequency range
Dimensional and charge characteristics of dispersions
of mesoporous silica in water. Dynamic and electrophoretic
light scattering were used to assess the dimensional and
charge characteristics of dispersions of pure MCM-41.
The concentration of the dispersed phase in the colloi-
dal system was selected empirically and was equal to
0.01 mg mL–1. A bimodal size distribution of aggregates
was observed for the given mesoporous silica content in the
system (Fig. 2). The majority of the formed aggregates
were particles with a hydrodynamic diameter Dh ≈ 175 nm,
with an insignificant (~5%) contribution of larger particles
with Dh ≈ 600 nm. The obtained results for the most
part satisfy the requirements imposed on drug carriers
(Dh  200 nm) adopted for prolonged circulation in the
circulatory system.
Electrophoretic light scattering demonstrated that
MCM-41 particles in an aqueous solution are negatively
charged (–40 mV, Fig. 3). This result indicates a high
stability of systems based on MCM-41 upon their disper-
sion due to the electrostatic repulsive forces preventing
particle agglomeration.
with a spectral resolution of 4 cm–1
.
Indomethacin encapsulated in mesoporous silica was studied
by simultaneous thermal analysis (thermogravimetry (TG)/dif-
ferential scanning calorimetry (DSC) in combination with in-
frared Fourier spectroscopy), in which the change in the sample
weight is recorded as a function of temperature and the corre-
sponding thermal effects are monitored. A coupled system of
a STA449-F3 TG/DSC simultaneous thermal analysis instrument
(Netzsch) and a Tensor 27 Fourier-transform IR spectrometer
(Bruker) ) was used in this work. The samples under study
(10.8—13.4 mg) were heated in a corundum crucible (Al2O3)
with a perforated lid from room temperature to 1000 C with an
empty crucible as a reference sample. The TG/DSC measure-
ments were carried out at a heating rate of 10 C min–1 in a stream
of argon of 50 mL min–1. The gas cell and the transport line
between the TG/DSC and the IR Fourier-transform spectro-
meter were heated to 200 and 195 C, respectively. The infrared
spectra of finely ground samples with KBr granules were re-
corded on a Tensor 27IR Fourier-transform spectrometer
(Bruker, Germany) in the 4000—400 cm–1 frequency range with
a spectral resolution of 4 cm–1
.
200 nm
Fig. 1. Micrograph of MCM-41 particles obtained using a scanning electron microscope.

Nanosized carriers based on mesoporous silica
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 7, July, 2019
1361
I (%)
Table 1. X-ray characteristics for MCM-41 type
mesoporous silica particles
30
Reflection
indices (hkl)
Interplanar
spacing (d/Å)
2θ/deg
100
110
200
210
33.985
19.834
17.136
13.022
2.598
4.452
5.153
6.783
20
10
technology, it is important to examine the rates of sedi-
mentation of MCM-41 suspensions in water. In the
first stage of study, electronic spectra of sedimentating
MCM-41 over time were recorded (Fig. 4). As can be seen,
silica particles sediment with time, which leads to a clear-
ing of the solution, i.e., to a decrease of absorption inten-
sity. The change in the optical density was the most notice-
able in the range of 200—400 nm, therefore, the sedimen-
tation kinetics was further studied at a wavelength of
300 nm, recording the dependence of optical density at
the given wavelength over time. The dependence obtained
over 5 min in the kinetic experiment is shown in Fig. 4
(see inset). Approximately 18% of the MCM-41 coarse
suspension sank over 5 min. At high contents of silica
particles in aqueous dispersions, most of the powdered
MCM-41 sank at a high rate, which is beyond measure-
ments. Due to this, these measurements can be made with
a considerably lower accuracy. Therefore, further studies
were carried out for systems with a low MCM-41 content.
For this purpose, the sedimentation kinetics of mesoporous
silica with a MCM-41 content of 0.06, 0.18, and 0.3 wt.%
were studied. The obtained results are shown in Fig. 5,
which indicate that at a minimum content of MCM-41
(0.06 wt.%), the changes in optical density over 10 min
are minor and the system is almost completely stable and
sedimentation is minimal. An increase in the content of
mesoporous silica to 0.18 and 0.3 wt.% considerably in-
creases sedimentation processes in the system, which is
1•102
1•103 Dh/nm
Fig. 2. Particle-size distribution for the suspension of meso-
porous silica in water averaged by the number of particles;
С = 0.01 mg mL–1; 25 С.
Note. Figures 2, 3 and 8 are available in full color on the
web page of the journal (https://link.springer.com/journal}/
volumesAndIssues/11172).
N•10–5
5
4
3
2
1
–1•102
0
/mV
Fig. 3. Electrophoretic light scattering results characterizing the
electrokinetic potential of particles in the mesoporous silica
suspension in water; С = 0.01 mg mL–1; 25 С; N is the number
of counts.
D
D300
3
Characterization of the sample by X-ray diffraction.
X-ray diffraction results (Table 1) confirm the presence
of an ordered hexagonal structure of the obtained meso-
porous silica sample. The presence of four reflections from
the planes (100), (110), (200), and (210) on the diffraction
pattern indicates a fairly high degree of hexagonal archi-
tecture in the sample. The interplanar spacing, calculated
from the positions of peak maxima, corresponds to a mean
hexagonal lattice parameter a equal to 39.4 Å. According
to literature, the lattice parameter a of MCM-41 type
mesoporous silica is in the range 40—54 Å.21,29,37,38
Sedimentation parameters of aqueous suspensions of
MCM-41. To assess the prospects for the use of suspen-
sions based on MCM-41 with an adsorbed drug in bio-
1.5
1.4
1.3
2
1.2
100
200
300 t/s
/nm
1
300
600
900
Fig. 4. Electronic absorption spectrum of MCM-41 sedimenta-
tion in water; 25 С.

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Russ. Chem. Bull., Int. Ed., Vol. 68, No. 7, July, 2019
Ibragimova et al.
D300
Table 2. Quantitative characteristics of indomethacin encapsula-
tion into MCM-41 mesoporous silica particles during the interac-
tion of components at temperatures 40 С (MCM-41@IMC-40)
and 60 С (MCM-41@IMC-60) obtained by various methods
0.4
0.3
0.2
1
2
3
Sample
TG analysis,
Spectrophotometry
m/mg g–1
Einc
Eload
%
MCM-41@IMC-40
MCM-41@IMC-60
28.6
41.8
53.0
99.6
17.7
22.3
200
400
600 t/s
Fig. 5. Kinetic sedimentation curves of aqueous dispersions of
MCM-41 with the dispersed phase content of 0.06 (1), 0.18 (2),
and 0.3 wt.% (3); 25 С.
(Table 2). It was shown that in both cases studied, a prac-
tically quantitative encapsulation of indomethacin into
the pores of the silica carrier was achieved with a high
(over 30%) drug loading efficiency. Thus, it can be argued
that the presence of a small amount of unbound indo-
methacin is a result of the drug removal from the pores of
MCM-41.
reflected in a substantial change in optical density com-
pared to the initial value. In this case, it can be deduced
that 30—45% of the starting amount of silica is involved
in sedimentation.
Spectrophotometric analysis of indomethacin encapsul-
ation. The content of encapsulated indomethacin in the
mesopores of MCM-41 silica was determined using
spectrophotometry. Figure 6 shows the results character-
izing the amount of indomethacin contained in ethanol
washings after the encapsulation of the drug into the carrier
pores over 3 h at a temperature of 40 and 60 С.
The presence of the drug in ethanol washings can result
either from a low degree of loading of indomethacin into
the pores of MCM-41 or from the removal of the adsorbate
from the primary adsorption sites located on the outer
surface and the inner walls of silica pores. The dominant
of these two factors can be determined from the results of
calculations based on spectrophotometric measurements
Study of adsorption—desorption of N2. The isotherms
of nitrogen adsorption—desorption and the size distribu-
tion of MCM-41 particle pores before and after the en-
capsulation of indomethacin are shown in Fig. 7. The
obtained adsorption pattern for silica particles in the
absence of a drug substance is a type IV isotherm charac-
teristic for mesoporous adsorbents.11 It was shown that in
both cases, the isotherms showed a sharp increase at
a relative pressure of 0.2  p/p0  0.4, which is related to
capillary condensation of nitrogen in the channels and to
a narrow size distribution of pores (Fig. 8). The analysis
of textural parameters of the MCM-41 and MCM-41@
IMC-40 samples determined by this method showed that
the transition from the first system to the second is ac-
D
b
3
2
1
0
m/g
a
0.15
0.10
0.05
300
400
500
600 /nm
T = 60 C
T = 40 C
Initial
amount
1
2
3
4
5
Washing cycle
Fig. 6. Change in the content of indomethacin (m) in washing ethanol with varying temperature and number of washing cycles de-
termined by spectrophotometry (a) and electronic absorption spectrum of washing ethanol containing non-encapsulated indometh-
acin (b).

Nanosized carriers based on mesoporous silica
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 7, July, 2019
1363
v/cm3 g–1
Table 3. Physicochemical characteristics of MCM-41 mesoporous
silica particles before and after contact with indomethacin
900
System
Pore
Pore
diameter*
/nm
Specific
surface area
/m2 g–1
1
2
volume*
/cm3 g–1
600
300
MCM-41
MCM-41@IMC
1.336
0.902
2.5
2.3
1927.1
1976.7
* Calculated using the BJH method.
(see Fig. 9). The bands at about 3454 and 1636 cm–1 are
related to stretching and bending vibrations of physio-
sorbed water, respectively. There is a characteristic narrow
band at 3745 cm–1 corresponding to vibrations of the OH
groups in isolated silanol groups and a weak band at
3650 cm–1 attributed to vibrations of terminal silanol
groups. The absence of a band at 3745 cm–1 is probably
due to a smaller number of defects in the silicon-oxygen
skeleton in the walls of large pores and, accordingly,
a smaller number of silanol group.
0.3
0.6
0.9 p/p0
Fig. 7. Nitrogen adsorption—desorption isotherms for MCM-41
mesoporous silica particles in the absence (1) and in the
presence (2) of encapsulated indomethacin.
v/cm3 g–1
2
IR spectra of indomethacin in the individual state (see
Fig. 9, spectrum 2) are characterized by the band maxima
related to stretching vibrations of the carbonyl fragment
of the carboxyl group (at 1714 cm–1), belonging to the
amide group (at 1692 cm–1), and characteristic vibrations
of carbon atoms of aromatic fragments (at 1479 cm–1).
After contact with indomethacin (see Fig. 9, spectra 3
and 4), the bands at 1706 and 1463 cm–1 appear in the
spectra of mesoporous silica samples, corresponding to
stretching vibrations of the carboxy С=O group and phenyl
fragments, respectively, which confirm that the drug was
successfully encapsulated into the mesoporous material.
In contrast to indomethacin in the free state, this system
demonstrates a considerable weakening of these bands and
their shift toward lower wavenumbers. This is probably
due to the fact that carboxyl and heterocyclic fragments
2
1
1
2
4
6
8 d/nm
Fig. 8. Pore-size distribution for MCM 41 mesoporous silica
particles in the presence (1) and in the absence of indometha-
cin (2), calculated using the BJH model.
companied by a decrease in the volume of adsorbed ni-
trogen (see Fig. 7), which indicates a partial filling of the
pores. Therefore, the corresponding values of specific
surface area and volume of pores of the mesoporous silica
sample decrease after the contact with indomethacin
(Table 3).
IR spectra. To characterize the encapsulated indo-
methacin in the mesopores of MCM-41 silica, IR spectra
were recorded for MCM-41@IMC system and its com-
ponents in the individual state (Fig. 9). Spectrum 1, cor-
responding to individual MCM-41, is typical of meso-
porous materials and contains their characteristic bands.
For example, the bands at 966 and 462 cm–1 correspond
to stretching vibrations of the Si—O bonds and bending
vibrations of the Si—O fragment of the surface Si—O—H
groups, respectively. In addition, antisymmetric stretching
vibrations of the Si—O—Si bonds at 1237 cm–1 located on
the surface of particles and within them can be clearly dis-
tinguished (1084 cm–1 (νаs SiO4) and 797 cm–1 (νsym SiO4))
T
4
1706
1463
3
1704
1714
1462
2
1
1479
4000 3500 3000 2500 2000 1500 1000 /cm–1
Fig. 9. IR spectra of MCM-41 type mesoporous silica in the free
state (1), individual indomethacin (2) and MCM-41 particles
after contact with indomethacin at a temperature of 40 (3) and
60 С (4).

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Ibragimova et al.
DSC/mW mg–1
in indomethacin molecules form hydrogen bonds with
silanol groups localized on the silicon dioxide surface. The
variation of IR band intensities from samples obtained
upon contact with the drug at different temperatures can
be explained by varying percentage of drug encapsulated
in the pores. Thus, the amount of drug bound to the carrier
can be regulated by varying the temperature of encapsula-
tion of the drug into mesoporous silica particles.
1
0
–0.4
–0.8
–1.2
DSC/mW mg–1
2
0
–5
–10
–15
TG analysis. To determine the amount of indometha-
cin encapsulated in the pores of silica particles, TG
analysis of MCM-41 in the free state and MCM-41 loaded
with indomethacin was carried out at temperatures 40 and
60 С (Fig. 10). The obtained TG curves indicate the dif-
ferent character of weight loss that occurs when МСМ-41,
MCM-41@IMC-40, and MCM-41@IMC-60 samples are
heated: the weight of the samples decreases from 95.6 to
85.5%. The initial loss of weight in all the samples in the
temperature range from 25 to 110 C corresponds to the
desorption of water molecules from the mesoporous
matrix. The matrix of pure MCM-41 silica in the studied
temperature range from 110 to 1000 C is thermostable
(see Fig. 10, curve 1) and the loss of weight (1.5%) occurs
in one step at 65.3 C. The presence of encapsulated in-
domethacin molecules in mesoporous silica particles led
to the appearance of endothermic peaks at 145.7 and
496.6 C for MCM-41@IMC-40 and MCM-41@IMC-60
(Fig. 11). The total weight loss over the temperature range
200—700 C, corresponding to the decomposition of in-
domethacin, was 2.86 and 4.18% for MCM-41@IMC-40
and MCM-41@IMC-60, respectively (see Fig. 10, curves
2 and 3). This indicates that when indomethacin contacts
with mesoporous silica at temperatures 40 and 60 С,
28.6 mg and 41.8 mg of the drug are encapsulated in 1 g
of MCM-41, respectively (see Table 1). This value is
considerably higher than the maximum amount of drug
encapsulated into MCM-41 particles found earlier.25
In conclusion, a MCM-41 type mesoporous material
was synthesized that is superior to the known analogs in
terms of specific surface and volume of pores. An efficient
protocol for the encapsulation of a hydrophobic drug was
developed using indomethacin as a test material. The
3
300
600
600
900 T/C
900 T/C
300
Fig. 11. DSC thermograms for МСМ-41 (1), MCM-41@IMC-40
(2), and MCM-41@IMC-60 samples (3); in the inset, a DSC
thermogram for individual indomethacin.
obtained results allow us to recommend the mesoporous
material described above as a promising carrier for a wide
range of lipophilic drugs.
The work was performed using the instrumental park
of the Spectral-Analytical Center of Shared Facilities for
Study of Structure, Composition and Properties of Subs-
tances and Materials of the Arbuzov Institute of Organic
and Physical Chemistry, a separate structural unit of the
Federal Recearch Center "Kazan Scientific Center of the
Russian Academy of Sciences".
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 18-03-00591).
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Received November 29, 2018;
in revised form February 20, 2019;
accepted March 7, 2019