Periodic mesoporous organosilicas with co-existence of diurea and sulfanilamide as an effective drug delivery carrier

Article abstract of DOI:10.1016/j.jssc.2011.03.003

In this article we report the synthesis of new periodic mesoporous organosilicas (PMOs) with the co-existence of diurea and sulfanilamide-bridged organosilica that are potentially useful for controlled drug release system. The materials possess hexagonal pores with a high degree of uniformity and show long-range order as confirmed by the measurements of small-angle X-ray scattering (SAXS), N₂ adsorption isotherms, and transmission electron microscopy(TEM). FT-IR and solid state ²⁹Si MAS and ¹³C CP MAS NMR spectroscopic analyses proved that the bridging groups in the framework are not cleaved and covalently attached in the walls of the PMOs. It was found that the organic functionality could be introduced in a maximum of 10 mol% with respect to the total silicon content and be thermally stable up to 230 °C. The synthesized materials were shown to be particularly suitable for adsorption and desorption of hydrophilic/hydrophobic drugs from a phosphate buffer solution at pH 7.4.

Full text of DOI:10.1016/j.jssc.2011.03.003

Journal of Solid State Chemistry 184 (2011) 1208–1215
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Journal of Solid State Chemistry
journal homepage: www.elsevier.com/locate/jssc
Periodic mesoporous organosilicas with co-existence of diurea and
sulfanilamide as an effective drug delivery carrier
Surendran Parambadath, Vijay Kumar Rana, Santha Moorthy, Sang-Wook Chu, Shin-Kyu Park,
Daewoo Lee, Giju Sung, Chang-Sik Ha n
Department of Polymer Science and Engineering, Pusan National University, Geumjeong-gu, Busan 609-735, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
In this article we report the synthesis of new periodic mesoporous organosilicas (PMOs) with the co-
existence of diurea and sulfanilamide-bridged organosilica that are potentially useful for controlled
drug release system. The materials possess hexagonal pores with a high degree of uniformity and show
long-range order as confirmed by the measurements of small-angle X-ray scattering (SAXS), N2
adsorption isotherms, and transmission electron microscopy(TEM). FT-IR and solid state 29Si MAS
and 13C CP MAS NMR spectroscopic analyses proved that the bridging groups in the framework are not
cleaved and covalently attached in the walls of the PMOs. It was found that the organic functionality
could be introduced in a maximum of 10 mol% with respect to the total silicon content and be
thermally stable up to 230 1C. The synthesized materials were shown to be particularly suitable for
adsorption and desorption of hydrophilic/hydrophobic drugs from a phosphate buffer solution at
pH 7.4.
Received 12 November 2010
Received in revised form
9 February 2011
Accepted 2 March 2011
Available online 21 March 2011
Keywords:
Periodic mesoporous organosilica (PMO)
Organic–inorganic hybrid materials
Diurea sulfanilamide
Drug delivery
Drug release
& 2011 Elsevier Inc. All rights reserved.
1. Introduction
materials. Co-condensation has been widely employed to introduce
different types of organic groups with specific functionality into
Periodic mesoporous organosilicas (PMOs) are considered as
derivative materials of mesoporous silica, which can be obtained
by condensation of organo-bridged silsesquioxane precursors in
the presence of organic soft templates [1]. These materials have
attracted increasing research attention in materials science
because of their homogeneous distribution of organic groups inside
the framework, high loading of organic groups, large surface areas
(up to 1000 m2 gꢀ1) and pore volumes (1 cm3 gꢀ1) [2]. In addition,
varying the processing parameters allows for the production of
materials with different appearances, such as films, powders, or
monoliths. Reactions with organic groups permit the functionaliza-
tion of the pore walls and therefore the chemical properties of the
materials [3]. However, due to the rigidity prerequisite for the
bridging groups and limited availability of the bridged silane
precursors, most of the organic bridging groups in the existing
PMOs are chemically inert. The chemical inertness of the typical
bridging groups widely used in PMOs offers few possibilities for
further chemical modification, greatly limiting their application. By
choosing the appropriate linker molecules it is also possible to
synthesize PMO materials that exhibit various new and interesting
properties, which is unknown in pure siliceous mesostructured
ordered mesoporous silica materials. The high loading rate and
uniform dispersion of organic moieties in the framework, as well as
various surface properties imparted from different functional groups
endow the PMO materials for various types of applications such as
catalysis, ion exchange, encapsulation of transition metal complexes,
chemical sensing, nano-material fabrications, and adsorption of
metal ions and drugs [4–8].
During the past three decades, controllable drug release system
which can deliver the therapeutic drugs to the targeted cells or
tissues in a controlled manner and enhanced drug efficiency with
reduced toxicity has attracted much attention. So far, a large variety
of materials, such as biodegradable polymers [9], hydroxyapatite
[10], calcium phosphate cement [11], hydrogels [12], and mesopor-
ous silica have been employed in controlled drug delivery systems
[13–15]. Among these drug delivery carriers, ordered mesoporous
silica (MS) materials are of special interest due to their stable
mesoporous structure, uniform and tunable pore size, high pore
volume, large surface area, nontoxic nature, easily modified surface
properties, and good biocompatibility. Recently urea bridged PMO
materials offer a good candidature in the adsorption of metal ions
and controlled drug delivery applications due to its hydrophilic
property and ease of synthesis [16–22]. There has been an ever
increasing interest in developing effective drug delivery systems
(DDS), largely driven by the need to improve effectiveness in
controlling the release rate. It is well recognized that an efficient
n Corresponding author. Fax: þ82 51 514 4331.
E-mail address: csha@pnu.edu (C.-S. Ha).
0022-4596/$ - see front matter & 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.jssc.2011.03.003

S. Parambadath et al. / Journal of Solid State Chemistry 184 (2011) 1208–1215
1209
delivery system should have the capability to transport the desired
guest molecules without any loss before reaching the targeted
location. Upon reaching the destination, the system needs to be
able to release the cargo in a controlled manner. Fabricating a
suitable material as carrier is one of the critical factor in controlling
the storage volume and release rate of a drug. Any premature
release of guest molecules poses a challenging problem. The drug is
usually deposited on the active site of the carrier materials by means
of Van der waal’s force of interaction, hydrophilic–hydrophilic or
hydrophobic–hydrophobic interaction [23–34]. In brief, periodic
mesoporous silicas (PMS), such as MCM-41 and SBA-15, have been
widely investigated as potential drug carriers [25–34], where
ibuprofen, itraconazole, gentamycin, cis-platinum, aspirin, captopril,
and 5-fluorouracil were used as model drugs to study the adsorption
and delivery processes. It is obviously advantageous, when using the
PMSs having organo-functionality for drug delivery applications
over conventional PMS materials. Particularly, sulfanilamide is the
starting material for several groups of drugs [35]. The original
antibacterial sulfonamides (sometimes called simply sulfa drugs)
are synthetic antimicrobial agents that contain the sulfonamide
group. On emphasizing this point the synthesis of PMO having
sulfanilamide functionality in its wall structure should be a promis-
ing candidate as a host for drug delivery application.
Here, we report the potential application of PMO materials
with bridging group having sulfonamide and urea functionalities
in the same molecule as effective drug carriers. Sulfanilamide
molecule was selected for modification by silane coupling reagent
to form the precursor. As is known, the amine functionality can
easily be coupled with isocyanato functionality at ambient con-
ditions. The synthesized N,N0-diureylene sulfanilamide (BSDU)
bridged periodic mesoporous hybrid material (SDPMOs), in which
the bridging group was uniformly distributed in the framework of
PMO material by co-condensation of tetraethyl orthosilicate
(TEOS) and BSDU using the Pluronic P123 surfactant as template.
We have used the materials for the adsorption and desorption of
drugs such as captopril and 5-Flurouracil at pH 7.4 to examine the
effectiveness of SDPMOs as a drug delivery system.
Scheme 1. Preparation of BSDU.
SiCH2CH2),
CH3CH2O),
d
d
3.0 (q, 4H, CH2NH),
d
3.3 (t, 8H, NHCH2)
d
3.7 (q, 12H,
4.3 (t, 2H, CH2NH, propylamine),
d
7.6–7.8 (q, 4H,
7.3 (CH3),
136.0 (NH–Cbenzene),
116.9 and 127.0 (Cbenzene),
NH), 2978 and 2885 cm
CO), 1552 cmꢀ1 NH–amide), 1401 cmꢀ1
SiC), 1314, 1159 cmꢀ1
SQO).
CHbenzene). 13C NMR (300 MHz, CDCl3):
d
0.38 (CH2Si),
d
d
d
18.5 (CH2),
d
23.5 (NCH2),
d
58.0 (CH2O),
d
146.9 (SO2–Cbenzene),
d
d
155.ꢀ81(CQO).
FT-IR (KBr): 3351 cmꢀ1
(n
(
(n
n
CH),
NC),
1681 cmꢀ1
1242 cmꢀ1
(n
(n
(n
(n
2.3. Synthesis of N,N0-diureylene-sulfanilamide bridged periodic
mesoporous organosilicas (SDPMO)
N,N0-diureylenesulfanilamide bridged mesoporous materials
were prepared using TEOS as the parent silica source, BSDU as
the source of bridging organic groups and P123 as the structure-
directing agent. A molar ratio of TEOS:BSDU:P123:HCl:H2O¼
(1ꢀx):x:0.017:4.79:185, where x¼0.025, 0.05, 0.075 and 0.10
has been used in the entire study. The materials synthesized
were named as SDPMO-2.5, SDPMO-5, SDPMO-7.5 and SDPMO-
10. In a typical procedure, a solution of P123, HCl and water was
prepared at 35 1C. To this solution, a mixture of TEOS and BSDU
were added slowly under vigorous stirring. The mixture was
allowed to stir for 24 h at the above temperature after the formation
of white precipitates, and further the heterogeneous mixture was
aged for 24 h at 100 1C under stirring conditions. The white
precipitates were recovered by filtration, washed with water and
then dried at atmosphere. The surfactant template was removed
from organosilica materials through solvent extraction from an
HCl–ethanol solution. 1 g of the as-synthesized PMO materials were
gently stirred for 24 h in a solution of HCl (36 wt%, 1.5 g) and 100 g
ethanol at 60 1C. This procedure was repeated three times until the
surfactants were totally removed. The powder was filtered, washed
with ethanol, and dried at 60 1C overnight to obtain final material.
2. Experimental section
2.1. Materials and reagents
Poly (ethylene oxide)-b-poly (propylene oxide)-b-poly (ethy-
lene oxide) [EO20PO70EO20
,
Pluronic P123, Mw¼5800], 3-
(triethoxysilyl) propylisocyanate (IPTES, 95%), tetraethyl orthosi-
licate (TEOS, 98%), sulfanilamide (99%), captopril (99%) and
5-Fluorouracil (5-Fu, 99%), acetonitrile, ethanol, HCl, phosphate
buffer solution (PBS), and simulated body fluid (SBF) buffer were
purchased from Aldrich, USA. All chemicals were used as received
without any further purification. Water used in all syntheses was
distilled and deionized.
2.4. Drug adsorption and release
2.2. Preparation of BSDU
Captopril/5-Fluorouracil (5-Fu) were dissolved in water
(10 mg/mL), and 0.1 g carrier material was added into 12 mL of
the above solution. The mixture was then shaken for 24 h at room
temperature, which was demonstrated to be long enough to reach
the adsorption equilibrium. The porous materials incorporated
with Captopril/5-Fu were collected by centrifugation, and washed
with water, and then dried in an oven at 35 1C. The amount of
drug loaded in the pores of the carrier was characterized quanti-
tatively using a thermogravimetric analyzer (TGA). In vitro drug
release experiments were carried out by placing the dried powder
of carrier materials loaded with drug molecules placed into a
dialysis membrane bag (molecular weight cutoff 5000 kDa), and
then immersed into 40 mL of phosphate buffer solution (PBS).
Sulfanilamide (1.72 g, 10 mmol) was dissolved in 40 mL of dry
acetonitrile. To this IPTES (4.62 g, 20 mmol), 10 mL of dry acet-
onitrile was added slowly under nitrogen atmosphere (Scheme 1).
The mixture was refluxed for 24 h under inert condition. The
reaction was monitored by TLC (thin layer chromatography)
analysis. The solvent was evaporated, followed by the production
of white precipitates, which were dispersed in dry hexane for 1 h.
The swelled white product was filtered, washed with hexane, and
dried under vacuum.
[(EtO)3Si(CH2)3NHCO]2SO2C6H4, Yield: 99%; 1H NMR (300 MHz,
CDCl3):
d 0.5 (t, 4H, SiCH2), d 1.1 (t, 18H, CH3CH2O), d 1.5 (t, 4H,

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S. Parambadath et al. / Journal of Solid State Chemistry 184 (2011) 1208–1215
Throughout our drug release study we have used the simulated
body fluid (SBF) buffer solution having a physiological pH of 7.4 at
37 1C. The released concentration as a function of time was
analyzed by UV–visible spectroscopy at 210/259 nm in SBF
solution.
2.5. Characterization
Small-angle X-ray scattering (SAXS) measurements were per-
formed using a synchrotron X-ray source of Pohang Accelerator
˚
Laboratory (PAL, Korea): Co-Ka (l¼1.608 A) radiation with an
energy range of 4–16 keV. Transmission electron microscopy (TEM)
images were obtained with a JEOL 2010 electron microscope with an
acceleration voltage of 200 kV. Scanning electron microscopy (SEM)
images were recorded with a JEOL 6400 microscope operating at
20 kV. Fourier-transformed infra-red (FT-IR) spectra were obtained
using a Perkin Elmer FT-IR spectrometer in the frequency range of
4000–400 cmꢀ1. The adsorption/desorption isotherms of nitrogen at
ꢀ196 1C were measured using a Nova 4000e surface area and pore
size analyzer. Before the measurement, the samples were degassed
at 120 1C for 2 h in vacuo. The pore size distribution curve was
obtained from an analysis of the adsorption branch using the
Barrett–Joyner–Halenda (BJH) method. 13C cross polarization (CP)
and 29Si MAS NMR spectra were obtained with a Bruker DSX400
spectrometer with a 4 mm zirconia rotor spinning at 6 kHz (reso-
nance frequencies of 79.5 and 100.6 MHz for 29Si and 13C CPMAS
NMR spectroscopy, respectively. A 901 pulse width of 5 ms, contact
time 2 ms, recycle delay 3 s for both 29Si MAS and 13C CP MAS NMR
spectroscopy have been utilized throughout the analysis). Thermo-
gravimetric analysis (TGA) was performed with a Perkin–Elmer Pyris
Diamond TG instrument at a heating rate of 10 1C minꢀ1 in air.
Fig. 1. Small angle X-ray scattering patterns of (a) SDPMO-2.5, (b) SDPMO-5, (c)
SDPMO-7.5, and (d) SDPMO-10.
3. Results and discussion
precursor there is an elongation and further aggregation has been
observed. The rope like morphologies of SDPMO-7.5 and SDPMO-
10 are the result of the electrostatic or hydrogen bonding
interaction between the organosilane present in the materials. A
deep inspection of SDPMO-7.5 and SDPMO-10 morphologies tells
the fact that there is an increased tendency for side on packing
due to the increase in hydrophilic urea and sulfanilamide func-
tionalities in the materials. SDPMO-2.5 and SDPMO-5 show a
3.1. Small angle X-ray scattering analysis (SAXS)
Fig. 1 displays the SAXS patterns of the samples SDPMO-2.5,
SDPMO-5, SDPMO-7.5 and SDPMO-10. All samples show three
scattering peaks that can be indexed as 100, 110 and 200
reflections, respectively, associated with hexagonal arrays of
mesopores [36], though a less intense scattering patterns were
obtained with increasing the fraction of the bridged disiloxane
precursor, indicating the weaker integrity of the two-dimensional
(2D) hexagonal mesostructure. The 110 and 200 scattering peaks
of the SDPMO-2.5, SDPMO-5 and SDPMO-7.5 were persisting, but
for SDPMO-10 the above peaks were not resolved fully due to the
partial structural demolish and the lack of long range order. The
above observation suggests that the presence of the excessive
complex organic building blocks inside the pore walls would
decrease the mesoscopic order of the PMOs and lead to the
collapse of the mesoporous structure.
particle length of 1.8 and 2.4
mm and a diameter of 0.6 and
1.6 m, respectively. Due to the particle aggregation nature of the
m
samples SDPMO-7.5 and SDPMO-10 was hard to clarify the exact
particle length and diameter.
3.3. N2-adsorption desorption study
Low temperature nitrogen adsorption–desorption isotherms
for 2D hexagonal (p6mm) SDPMOs are shown in Fig. 3A. All
isotherms displayed type IV patterns with steep capillary con-
densation/evaporation steps at P/P0 of 0.65–0.80 and obvious H1
hysteresis loops, characteristic of mesoporous materials according
to the IUPAC classification. The BET surface areas for this series of
SDPMOs are in the range from 611 to 100 m2 gꢀ1, and the total
pore volumes vary from 1.01 to 0.12 cm3 gꢀ1 (Table 1). As seen
from Fig. 3A, and B, the sorption isotherm and the corresponding
pore size distribution change gradually for the SDPMO samples
from SDPMO-2.5 to SDPMO-10. The capillary condensation step
shifts to lower P/P0 values with increasing concentration of BSDU
in the initial sol mixture, suggesting the gradual decreasing of the
pore diameter from SDPMO-2.5 to SDPMO-10 and having a
relative pressure range of P/P0¼0.43–0.56. This is expected
because of the geometrical constrictions to accommodate a large
number of lengthy BSDU bridging groups in the mesopore walls of
the SDPMOs. The specific surface area of SDPMOs decreases from
3.2. TEM and SEM images
Representative TEM images of SDPMO-7.5 and SDPMO-10
shown in Fig. 2A provides excellent evidences for the periodic
hexagonal arrangement of the PMOs after surfactant extraction,
which is consistent with the SAXS patterns. The sample SDPMO-
7.5 shows good long range order, confirming the 2D hexagonal
mesostructure [37]. But the SDPMO-10 shows a disordered pore
structure in the TEM image, which may be due to the partial
destruction to the channels. The SEM images shown in Fig. 2B
demonstrate a morphology transition trend of the PMOs with the
increase of BSDU. For SDPMO-2.5, the morphology is somewhat
irregular short rods, while going to higher loading of the disilane

S. Parambadath et al. / Journal of Solid State Chemistry 184 (2011) 1208–1215
1211
Fig. 2. (A) Transmission electron microscopic images of (a) SDPMO-7.5 and (b) SDPMO-10 and (B) Scanning electron microscopic images of (a) SDPMO-2.5, (b) SDPMO-5,
(c) SDPMO-7.5 and (d) SDPMO-10.
Fig. 3. (A) N2 adsorption–desorption isotherms and (B) Pore size distributions of (a) SDPMO-2.5, (b) SDPMO-5, (c) SDPMO-7.5 and (d) SDPMO-10.

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S. Parambadath et al. / Journal of Solid State Chemistry 184 (2011) 1208–1215
Table 1
Physico-chemical properties of diureylene–sulfonamide bridged mesoporous
organosilica from N2-sorption analysis.
Material
Specific surface
Pore diameter
Pore volume
(cm3 gꢀ1
)
area (m2 gꢀ1
)
˚
(A)
SDPMO-2.5
SDPMO-5.0
SDPMO-7.0
SDPMO-10.0
611
403
311
100
61
59
56
48
1.01
0.63
0.44
0.12
663 to 100 m2 gꢀ1 with an enlargement of the diureylene–
sulfanilamide moiety contents in the framework. It is worthy to
mention that all SDPMO materials synthesized with different
fractions of BSDU have ordered mesostructure with uniform pore
size distributions. The pore diameter and pore volume of SDPMO-
2.5, SDPMO-5, SDPMO-7.5 and SDPMO-10 were calculated toꢀb1e
3
˚
61, 59, 56 and 48 A and 1.02, 0.63, 0.44 and 0.12 cm g
,
respectively, decreasing with the fraction of BSDU. BSDU has a
large molecular size and the bulk organic groups which can
occupy more space of the mesopore walls in the case that a large
amount of the guest is incorporated in the composite, resulting in
a large reduction of the pore diameter and volume [1,38,39]. By
increasing the BSDU fraction, more organic groups were incorpo-
rated into the silica matrix, leading to a SDPMO-10 with a
broaden distribution of the pore size and a slightly distorted
hexagonal mesostructure. The results are well consistent with the
results of SAXS and TEM. Asefa et al. [38] reported that the surface
area and pore volume did not decrease so much by increasing the
loading amount of organic functional groups. Thus the sharply
decrease of the surface area and pore volume with increasing the
BSDU fraction may be caused by the damage of the mesostruc-
ture. However, the surface area or pore volume is strongly
dependent on the type of organic moiety inside the PMO material.
In the present study the organic molecule used is highly inter-
active and thus a regular packing would be possible in both walls
and pores due to the presence of various functional groups
therein. The plausible formation of hydrogen bonded interaction
in this type of molecule may also cause a decrease in pore volume
and surface area.
Fig. 4. FTIR spectra of (a) SDPMO-2.5, (b) SDPMO-5, (c) SDPMO-7.5 and
(d) SDPMO-10.
3.5. Solid state 29Si MAS and 13C CP MAS NMR analysis
Solid-state 29Si MAS NMR spectrum (Fig. 5a) of the surfactant-
extracted SDPMO-7.5 material confirmed the successful incorpora-
tion of the covalently anchored organic groups in the framework.
Two groups of signals can be distinguished in the spectrum:
(a) three Q signals from silicon atoms without organic substitution
and (b) two T signals related to organo-substituted silicon. The Q
signals at ꢀ86, ꢀ94, and ꢀ101 ppm were assigned to Q2, Q3, and
Q4 structures, respectively. The Q3 signal, corresponding to SiO3OH,
is clearly dominating, while the Q4 signal caused by SiO4 groups
generated from fully condensed silanol groups. The Q2 signal, related
to partially condensed SiO2(OH)2, contributes with less percentage
[48–50]. The signals originating from silicon bridged by the organic
group can be found in the range from ꢀ45 to ꢀ90 ppm, thus
confirming the incorporation of organic groups inside the frame-
work [51]. The signals at ꢀ59 and ꢀ65 ppm can be assigned to the
silicon resonances of partially condensed T2 [(SiO)2(OH)SiC] and
fully condensed T3 [(SiO)3SiC] sites, respectively, indicating both the
presence of organic moieties inside the framework and the high
degree condensation of the silanol groups.
3.4. FTIR analysis
The FTIR spectra of solvent extracted SDPMO-x samples are
shown in Fig. 4. In all the samples a broad and strong band at
3405 cmꢀ1 can be due to N–H stretching vibration. The vibration
bands at 2900–3000 cmꢀ1 are assigned to the CH stretching
vibrations of propyl and sulfanilamide moieties [1,4,5]. A sharp
and intense band at 1646 cmꢀ1 is attributed to the CQO stretching
vibration of the urea group [40–43]. The bands at 1557 cmꢀ1
together with 690 cmꢀ1 result from the presence of the bending
vibration of N–H, while the band at 1412 cmꢀ1 is the characteristic
of an N–C functional moiety inside the material [44]. The band from
1100–1000 cmꢀ1 can be attributed to Si–O–Si stretching vibration,
and the band at 670 cmꢀ1 should be related with a bending
vibration of O–Si–O bond. The results indicate the hydrolysis and
co-condensation of the Si–OCH2CH3 groups. The intensity of
1700–1500 cmꢀ1 bands increases gradually from the SDPMO-2.5
to the SDPMO-10 sample, which signifies the increased concentra-
tion of urea groups in the resultant materials. Moreover, a strong but
broad band at 1250 cmꢀ1 in all the samples for the vibration of Si–C
indicates that the Si–C bond has not been broken during the
synthesis process [45–47]. The weak bands at 2900–3000, 1348
and 1377 cmꢀ1 not only implies the presence of C–H moieties but
also the complete removal of P123 surfactant by ethanol extraction.
Fig. 5b exhibits the 13C CP–MAS NMR spectrum of the SDPMO-
7.5 sample after solvent extraction. Three signals (0–50 ppm) are
observed, due to the Si–CH2CH2CH2– groups, demonstrating the
presence of the Si–C bond. The resonance at 10.5 ppm is attrib-
uted to –CH2, which is directly bonded to a Si atom. The
resonance at 17.6 ppm represents –CH2, at 24.2 ppm for a –CH2
carbon atom directly bonded to the –NH group, respectively.
Furthermore, the resonance of CQO at 158.6 ppm can also be
observed with a weak intensity in SDPMOs. The existence of the
phenyl group is identified from the remaining signals in the
spectrum, i.e.,
d¼61.1, 72.7 and 76.1 ppm. The clear resolution
of the four carbons can be attributed to the homogeneous
conformation of the organic groups in the pore walls [52].
3.6. SDPMOs as drug delivery system
Fig. 6 shows the in vitro release profile of captopril and
5-fluorouracil at 37 1C from the samples SDPMO-2.5 and
SDPMO-7.5 into the simulated body fluid (SBF) at pH¼7.4.
Captopril/5-fluorouracil has been introduced in both materials
(SDPMO-2.5 and SDPMO-7.5), in order to study the influence of
organosilica loading, pore size and particle morphology in drug

S. Parambadath et al. / Journal of Solid State Chemistry 184 (2011) 1208–1215
1213
release. The quantities of captopril/5-fluorouracil adsorbed were
measured by UV–vis spectroscopy and TG analysis {Fig. 7(A) and
(B)}, which revealed amounts of 6.23 and 9.72 wt% in the case of
captopril and 12.23 and 13.71 wt% in the case of 5-fluorouracil for
SDPMO-2.5 and SDPMO-7.5, respectively. For comparison, the TG
curves for SDPMO-7.5 without loading any drug are illustrated in
Fig. 7 to show the removal of organic moieties due to the presence of
organosilane in the material as a representative SDPMO, though the
SDPMO materials synthesized with different molar ratio of BSDU/
TEOS may show different weight loss. Upon heating under air, the
SDPMO-7.5 without drug loading undergoes a total weight loss of
21%. The initial weight loss, until 393 K, was attributed to thermal
desorption of water and another weight loss in the range of
393–506 K indicates the removal organic moieties due to the
presence of organosilane in the material. Presumably, the rather
extended temperature range is caused by several chemical reactions
(e.g. urea decomposition, sulfonyl decomposition, oxidation reac-
tions, and ‘‘channel metamorphosis’’) via proton transfer from
silanols to methylene groups [48,53]. Even after loading drugs,
similar TG patterns were observed for the typical SDPMO-7.5 except
the further weight losses due to the decomposition of the
loaded drugs. It is noteworthy that for the small-pore material
(SDPMO-7.5), the apparent weight of captopril/5-fluorouracil mole-
cule packed inside is higher than the large pore sized material
(SDPMO-2.5) even though the material having less surface area.
These results suggest a solid relation between the amount of
organosilane loading and nature of the drug molecule, besides the
particle size, pore diameter and surface area of the host material.
It has been shown elsewhere [54] that the driving force for the
inclusion of captopril/5-fluorouracil inside the PMOs seems to be
the hydrogen bond interaction between the captopril/5-fluorour-
acil molecule and the imine, sulfonyl or carbonyl functionality of
the organo-bridged molecule in the pore wall. Moreover, 5-Fluor-
ouracil having fluorine atom (exhibiting
a strong hydrogen
bonding) in the heterocyclic ring would create stronger hydrogen
bonds with organo-bridged molecule in the pore wall than
captopril and therefore results in the high drug loading. This is
why the amount of 5-fluorouracil loading is higher than captopril
for both PMOs under our experimental conditions.
It can be observed that all the release profiles are similar and
exhibit sustained release bahaviors. The samples having pore
diameters of 6.1 and 5.6 nm and block-and-rope like morphologies
for SDPMO-2.5 and SDPMO-7.5, respectively. It was generally
observed that increasing the pore size of the host material leads to
a faster drug release rate and vice-versa. Therefore, in our study, a
slower drug release rate has been observed while going from
SDPMO-2.5 to SDPMO-7.5. The long mesoporous channel for the
sample SDPMO-7.5 and higher % of BSDU organosilane are also
favorable factors for the slower release of captopril/5-fluorouracil
molecules [33,54]. The drug release process can be presumed to be
mainly diffusion controlled. On the one hand, the release medium
penetrates into the drug-matrix phase through pores; on the other
hand, the drug dissolves into the release medium and diffuses from
the system along with the solvent filled pore channels. This process
is practically supported by the hydrophilic nature of the silica
Fig. 5. (a) 29Si MAS and (b) 13C CP-MAS NMR spectra of SDPMO-7.5.
Fig. 6. (A) Captopril and (B) 5-Fluorouracil release profiles from (a) SDPMO-2.5 and (b) SDPMO-7.5.

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S. Parambadath et al. / Journal of Solid State Chemistry 184 (2011) 1208–1215
Fig. 7. TGA curves of (A) captopril and (B) 5-fluorouracil loaded (a) SDPMO-2.5 and (b) SDPMO-7.5. For comparison, TGA curves of SDPMO-7.5 without any drugs are also
presented (dotted lines denoted as ‘‘no drug.’’).
surface and the diureylene bridge molecule in the pore wall of the
PMOs. Additionally, a large difference in the initial drug release rate
for both PMOs is observed. For instance, the captopril release
occurred 43% within 4 h while only 26% of 5-fluorouracil was
released from the sample SDPMO-2.5. After the initial release, a
slower desorption was observed for captopril while a drastic release
occurred for 5-fluorouracil. This may be due to the less interaction
between 5-fluorouracil with diureylene molecules than with capto-
pril. The drug release from the sample SDPMO-2.5 seems to be
completed within 48 h, particularly for 5-fluorouracil no release had
been observed after 36 h. The drug release profile from the sample
SDPMO-7.5 is strictly in a controlled manner for both captopril and
5-fluorouracil. When comparing the initial desorption behavior
of both the drugs, 18% of 5-fluorouracil was released while 28% of
captopril was released within 4 h. After that, a reduced amount of
drug release was observed for both the drugs, which may be due to
many favorable factors such as particle size, pore diameter, a greater
amount of organosilane loading, and longer channels of the SDPMO-
7.5 than SDPMO-2.5. Therefore, it can be concluded that the drug
release behavior from the host material is governed by the mor-
phology, the amount of organo-bridged molecules, the pore dia-
meter, etc. [30].
The nature of the drug molecule and its interaction with the
host matrix also plays an important role in controlled release
[30,39]. Captopril/5-fluorouracil drug chosen in the present study
is that the first one (Captopril) is highly hydrophilic and the
second one (5-Fu) is weakly hydrophilic. Nevertheless, 5-Fluor-
ouracil would create stronger hydrogen bonding with the diur-
eylene molecule due to the presence of fluorine atom in the
heterocyclic ring of its molecular structure than captopril.
Meanwhile, SBA-15 is another important mesoporous material
with large, controlled pore size and highly ordered hexagonal
topology. The pore size of SBA-15 is usually large. Therefore,
SBA-15 is expected to have less restriction for the delivery of
bulky molecules compared to SDPMOs. However, for pure SBA-15,
there exist only silanol groups on the channel walls, and these
silanol groups simply form weak intermolecular hydrogen bonds
with drugs, hence, they are not strong enough to hold drugs and
allow them to be released in a sustained manner [55]. Therefore,
introduction of functional groups on the surface of SBA-15 to have
specific host–guest interactions with drugs will also be important
and desirable for controlled drug delivery [56].
condensation of TEOS and BSDU precursors in presence of Pluronic
P123 as a template. The as-prepared SDPMO samples conserve
regular rope-like morphology, and exhibit mesoporous structure,
which is suitable for controlled release as a drug carrier. The
combination of several characterization techniques have demon-
strated that diurea sulfanilamide bridged molecule has been suc-
cessfully incorporated in the wall of the PMO materials. Also it was
confirmed that a maximum amount of organic groups incorporated
into the PMOs reached up to 10 mol% according to the total silane
content. However the incorporation of the complex organic group
would slightly decrease the macroscopic order. Anyway, the drug
release process from the matrix into a simulated body fluid (SBF)
solution showed that the diurea sulfanilamide modified PMO
materials are well controlled due to the presence of hydrophilic
ureylene moieties, which supports the potential use of the materials
as suitable controlled drug delivery carriers at a pH 7.4.
Acknowledgments
This work was supported by the Ministry of Education, Science
and Technology (MEST) through the National Research Foundation of
Korea (NRF) with the Acceleration Research Program (No. 2010
0000790), the Pioneer Research Center Program (2010-0019308/
2010-0019482), and the Brain Korea 21 Project of the MEST.
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