sacrificial sulphonated polystyrene template-assisted
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Sacrificial sulphonated polystyrene template-assisted synthesisof mesoporous hollow core-shell silica nanoparticles fordrug-delivery application
DEEPIKA DODDAMANI and JAGADEESHBABU PONNANETTIYAPPAN*
National Institute of Technology Karnataka, Surathkal, Mangalore 575025, India
*Author for correspondence (dr.jagadeesh@yahoo.co.in)
MS received 7 September 2019; accepted 19 January 2020
Abstract. Spherical mesoporous hollow core-shell silica nanoparticles (HCSNs) of size 200 ± 50 nm with tunable
thickness from 20 to 60 nm are synthesized using a sacrificial sulphonated polystyrene (PS, particle size 160 nm)
template. A facile method is adopted for the sulphonation of PS using sulphuric acid, which enhanced the negative
charge on the surface of PS as confirmed by zeta potential analysis and Fourier transform infrared radiation analysis.
The thickness of the silica shell is tuned by altering the concentration of the silica precursor and is found to increase
due to the use of the sulphonated PS template. N2 adsorption/desorption studies reported the variation of specific
surface area of HCSNs from 644.1 to 197.8 m2 g-1 and average pore size from 1.55 to 3.4 nm. The drug release
behaviour of HCSNs with different shell thicknesses is investigated using doxorubicin as the model drug. A delay in
the drug release for *300 min is successfully achieved by employing HCSNs with enhanced thickness of 60 nm.
Application of HCSNs in targeted drug delivery was further supported by the in-vitro cytotoxicity studies carried out
on lung adenocarcinoma cells.
Keywords. Hollow core-shell silica nanoparticles; polystyrene; drug delivery.
1. Introduction
Hollow core-shell silica nanoparticles (HCSNs) have made
notable impact in the field of targeted drug-delivery systems
due to the following properties; tunable morphology, large
specific surface area and biocompatibility [1–3]. Promising
applications of HCSNs also include catalysis, chromato-
graphic separations, membranes, electronic devices and
sensors [2–6]. Various synthesis techniques have been dis-
cussed in the literature to synthesize HCSNs, like sacrificial
template, hydrothermal, sol/gel and sonochemical tech-
niques [7–9].
Sacrificial template method is one of the efficient
methods for the synthesis of nanosized hollow core-shell
silica-structured particles. In this template method, mor-
phology of silica nanoparticles could be tuned by varying
parameters such as size, shape and surface properties of
the template. Thus, sacrificial template methods provide a
flexible route to synthesize HCSNs with tunable mor-
phology. Various templates used during the synthesis of
HCSNs include polystyrene (PS), PS-b-poly(acrylic acid),
cetyltrimethylammonium bromide (CTAB), PS-methyl
acrylic acid, liposomes and ZnSe [7–11]. Among them PS
is a versatile template using which morphology of silica
shell could be improved by varying the surface charge of
the sacrificial template. Surface properties of PS tem-
plates were modified by functionalization of PS such as
carboxyl, amino, sulphonate and nitro functional groups
[7–9]. Yang et al [8] used microspheres of sulphonated
PS to synthesize hollow polyaniline and hollow poly-
pyrrole particles. Sulphonated PS silica composites were
employed as ion-exchange materials, adsorption of metal
ions and solid acid catalysts [10–12]. Liu et al [13]
reported synthesis of hollow porous silica particles using
sulphonated PS-methyl acrylic acid template. Utilization
of sulphonate functionalized PS nanoparticles during the
fabrication of HCSNs for use in the field of drug delivery
requires a detailed study.
The synthesis of monodispersed silica spheres by Stober
method involved hydrolysis-condensation of tetraethyl
orthosilicate (TEOS) in water–ethanol mixture using
ammonia as a catalyst [14]. Stober method was altered by
the use of polymeric template and cationic surfactant to
synthesize nanometer or sub-micrometre-sized hollow silica
spheres [15,16]. Various precursors of silica used during the
synthesis were tetramethoxysilane, tetraethoxysilane and
colloidal silica particles [17–19]. Facile synthesis of HCSNs
by merging the template and Stober methods resulted in the
formation of HCSNs with tunable thickness and narrow
pore size. These features were explored while HCSNs were
Bull Mater Sci (2020) 43:213 � Indian Academy of Scienceshttps://doi.org/10.1007/s12034-020-02209-0Sadhana(0123456789().,-volV)FT3](0123456789().,-volV)
used as drug-delivery vectors [20,21]. HCSNs received
much attention among various drug-delivery systems such
as liposomes, dendrimers, nanotubes and hydrogels
[22–25]. HCSNs were found to have good biocompatibility
and chemical stability which fit the basic requirements of
the targeted drug-delivery systems. The tunable morphol-
ogy of mesoporous silica nanoparticles permitted incorpo-
ration of drug particles and targeted drug delivery to the
sites of disease [26,27].
The synthesis of HCSNs with enhanced shell thickness
using sulphonated PS template, lead to the delayed release
of drug is comparatively less studied in the field of targeted
drug delivery. In this research study, sulphonation of PS is
carried out to improve the surface charge properties of PS.
Sulphonated PS is used as a template to synthesize the
HCSNs with enhanced thickness by modified Stober
method. A detailed investigation is conducted to analyse the
influence of sulphonated PS on variation of surface area and
shell thickness of mesoporous HCSNs. A systematic study
is conducted to determine the drug loading and release
behaviour in controlled form for HCSNs at different shell
thicknesses. Cytotoxicity studies were conducted for
HCSNs, doxorubicin (DOX) loaded HCSNs and DOX on
lung adenocarcinoma (A549) cells.
2. Materials and methodology
2.1 Materials
Styrene (99%), polyvinyl pyrrolidone (PVP, 40,000-
molecular weight), TEOS (98%) and DOX were obtained
from Sigma Aldrich. Sulphuric acid (98%), potassium per
sulphate (KPS, 98%) and CTAB (98%) were purchased
from Loba Chemie. Aqueous ammonia solution (25%) and
ethanol (99%) were procured from Spectrum Chemicals and
Changshu Hongsheng Fine Chemical Co. respectively. All
the chemicals were used as collected without any treatment.
Purified water was obtained from a Millipore purification
apparatus.
2.2 Methods
2.2a Synthesis of sulphonated PS template: PS nanopar-
ticles were synthesized by using emulsion polymerization
method as previously described in the literature [28] by
employing styrene as a monomer, KPS as the initiator
and PVP as a stabilizer. One gram of synthesized PS was
dispersed in a mixture of 0.15 moles of concentrated
sulphuric acid and 27.7 mmoles of water. The reaction
was performed at room temperature for 2 h. Ethanol was
added in excess to resume the sulphonation and stirred
for 30 min. Sulphonated PS nanoparticles were washed 6
times in water by centrifugation at 12,000 rpm for
10 min. The samples were dried in a vacuum drier to
remove the moisture adsorbed.
2.2b Synthesis of HCSNs: HCSNs were synthesized using
sulphonated PS as a template. One gram of synthesized
sulphonated PS template was allowed to disperse in water—
ethanol mixture maintained at a ratio of 4:1 by using
ultrasonication for 30 min. A volume of 10 ml of 5%
solution of CTAB was added to the mixture followed by
magnetic stirring for 3 h. A measure of 0.5 ml of ammonia
was added to the solution preceded by the addition of
TEOS–ethanol mixture in the ratio of 1:1. Magnetic stirring
was continued for 4 h at room temperature. Thus obtained
suspension was aged at room temperature for 24 h. The
precipitate containing silica-coated sulphonated PS was
separated by centrifugation (10,000 rpm for 15 min) and
washed five times with water. Resulting samples were dried
in a vacuum drier to remove moisture content and calcined
at 550�C for 4 h at a heating rate of 1�C min-1 to remove
sulphonated PS core.
2.2c Loading and release studies: A 50 mg of HCSNs
were dispersed in 100 ppm solution of DOX by ultrasoni-
cation for 3 min and stored at 4�C for 48 h. DOX-loaded
HCSNs were separated by centrifugation (at 12,000 rpm for
15 min) and dispersed in phosphate-buffered saline (PBS)
of pH-7.4. The samples were stirred mildly at 37�C. A
volume of 5 ml of solution was withdrawn at known time
intervals and centrifuged at 12,000 rpm for 5 min to study
the release behaviour of DOX. The supernatant was anal-
ysed in a UV–visible spectrophotometer at a wavelength of
480 nm and it was poured back to maintain the constant
volume. The release studies were carried out at pH 6 using
phosphate buffer (PB), to study the effect of pH on the
release.
A volume of 1 litre PBS buffer at pH 7.4 is prepared by
dissolving 0.137 mol of NaCl, 2.7 mmol of KCl, 0.01 mol
of Na2HPO4 and 1.8 mmol of KH2PO4 in water using a 1 L
volumetric flask. PB buffer at pH 6 is prepared by mixing
95 ml of 0.1 M KH2PO4 and 5 ml of 0.1 M Na2HPO4 in
water using 1 L volumetric flask.
2.2d In-vitro cytotoxicity assays: The in-vitro cytotoxicity
studies were carried out by 3-(4,5-dimethylthiazol-2-yl)-
2,5-diphenyltetrazolium bromide (MTT) assay method for
HCSNs and SPION embedded HCSNs. Lung adenocarci-
noma (A549) cells were procured from National Center for
Cell Sciences (NCCS), Pune. They were cultured in Dul-
becco’s modified Eagle’s medium (DMEM) supplemented
with 10% fetal bovine serum (FBS) and 1% antibiotic
antimycotic solution. The cells were maintained at 37�Cwith 5% CO2 in a humidified atmosphere. The cells were
seeded onto 96-well microtitre plates at a seeding density of
5000 cells per well. After adherence, they were treated with
different concentrations of the HCSNs samples such as 25,
50, 100 and 200 lg ml-1. MTT assay reagent was added
and incubated at 37�C for 4 h, after 48 h of post incubation
213 Page 2 of 9 Bull Mater Sci (2020) 43:213
period. Formazan crystals formed were solubilized using
dimethyl sulphoxide and absorbance was recorded at
570 nm using a multimode microplate reader (FluoSTAR
Omega, BMG labtech). Percentage viability of the test
compounds was calculated with respect to the cell control.
2.3 Characterization techniques
HCSNs were gold sputtered and observed under a scanning
electron microscope (SEM, JEOL-JSM 6380 LA) to study
the surface morphology. HCSNs were dispersed in ethanol
by ultrasonication and a few drops were added to the carbon
coated copper grid prior to visualization in transmission
electron microscopy (TEM, JEOL JEM-2100). Horiba (SZ-
100) instrument was used to find out the zeta potential and
particle size, by dispersing the samples in distilled water by
ultrasonication. Zeta potential was determined at pH 7 and
average of three measurements were calculated with the
standard deviation and conductivity. The autocorrelation
function for dynamic light scattering is given as
G2 sð Þ ¼ I tð Þ � I t þ sð Þ; ð1Þ
where G2(s) is the autocorrelation function, I(t) representsscattering light intensity and s is the short time difference.
Surface area analyser (Quantachrome Corporation,
NOVA1000) was used to study N2 adsorption/desorption
isotherms of the HCSNs. The specific surface area and
the pore-size distribution were calculated by Brunauer–
Emmett–Teller (BET) and Barrett–Joyner–Halenda (BJH)
methods, respectively. The sample preparation involved
degassing of samples under a vacuum at 450�C for 8 h and
the analysis was performed at 77 K. Fourier transform
infrared spectra of PS, sulphonated PS, silica-coated sul-
phonated PS and HCSNs were recorded in Thermonicolet
Avatar-370 using KBr pellet method. Thermogravimetric
analysis (TGA) was carried out using TG/TGA instrument
(Hitachi-6300) with a heating rate of 10 K min-1 from
room temperature to 750�C in the presence of air. The DOX
release behaviour of HCSNs was observed in UV–visible
spectrophotometer (Hitachi, U-2900).
3. Results and discussion
3.1 Synthesis and characterization of HCSNs
FTIR absorption spectra of PS, sulphonated PS, silica-
coated sulphonated PS and HCSNS are presented in
figure 1. The peaks at 696 and 754 cm-1 correspond to
vibrations (C–H) of the benzene ring and those at 1493,
1451 and 1600 cm-1 are attributed to vibrations of benzene
ring (C–C) of PS [29,30] (figure 1a). Sulphonation of PS is
confirmed by the occurrence of a strong absorption band at
1170 cm-1 (figure 1b) corresponding to the sulphonic
group (–SO3H) [13,31]. Figure 1f shows the chemical
structure of sulphonated PS according to Mulijani et al [32].In figure 1c, a peak at 951 cm-1 reveals that CTAB is
coated on sulphonated PS nanoparticles [33]. Figure 1d
shows FTIR spectrum of HCSNs. The sequence of
absorption bands comprising of 1093 and 804 cm-1 belong
to Si–O–Si asymmetric and symmetric stretching vibration.
The presence of silanol groups (Si–OH) on the surface is
confirmed by the peak at 962 cm-1. The oxygen deforma-
tion vibration (Si–O–Si) is observed from the band at
460 cm-1 [34]. The bands due to alkyl groups vanish in
HCSNs in the range of 2800–2900 and 2900–3000 cm-1
which is in agreement with the complete removal of sul-
phonated PS core during the process of calcination [35].
HCSNs have chemical structure with Si–O–Si and Si–OH
bonds as given in figure 1e [36]. Si–OH bonds face towards
the surface of the shell.
SEM images of PS and sulphonated PS are displayed in
the figure 2a and b which show monodispersity and spher-
ical morphology of the samples are retained even after
sulphonation. PS and sulphonated PS showed an average
particle size of 140 and 160 nm, respectively (figure 2c and
d). An increase in the size of sulphonated PS could be due
to the increase in hydrodynamic diameter of the particles, as
there was an increase in the number of functional groups on
the surface of the sulphonated PS. The zeta potential anal-
ysis results of PS and sulphonated PS are shown in table 1.
There was *11.7 mV decrease in the zeta potential after
the sulphonation of PS, attributed to the presence of sul-
phonic groups.
The TEM images of HCSNs synthesized by altering the
ratio of PS/TEOS (1:1, 2:3, 4:7 and 1:2) are shown in fig-
ure 3. Silica nanoparticles exhibited a structure containing
hollow internal core and thick shell confirmed by the TEM
images (figure 3a–d). High-resolution TEM images were
also captured for the HCSNs samples to observe the pres-
ence of the silica shell (figure 3a–c).
The concentration of silica precursor and surface charge
of template play a key role in tuning the shell thickness
of HCSNs. During the synthesis step of HCSNs, TEOS
hydrolysed and deposited on the surface of CTAB-coated
sulphonated PS. The thickness of silica shell was found to
increase from 20 to 60 nm with increase in quantity of
TEOS from 1 to 1.75 g while PS/TEOS ratio varied from
1:1 to 4:7 (figure 3a–c). When the concentration of TEOS
was enhanced, additional amount of silica was deposited on
the surface of sulphonated PS which enhanced the thickness
of the shell [28,37]. Shell thickness of HCSNs synthesized
using the sulphonated PS template was found to be higher,
compared to that of HCSNs synthesized using PS template
[28]. This phenomenon accounted to the increase in
attractive force between the positively charged CTAB and
negatively charged silica ions.
The presence of sulphonic acid group enhanced the
negative charge on the surface of PS as confirmed by zeta
potential analysis. This phenomenon might have enhanced
the deposition of CTAB on the surface of sulphonated PS.
Bull Mater Sci (2020) 43:213 Page 3 of 9 213
Thus, a higher thickness of silica shell was attained using
sulphonated PS as the template. The silica shell thickness
was found to increase with increase in the acidity of acidic
functional group [13]. Further increase in the concentration
of TEOS (PS/TEOS ratio of 1:2) lead to the evolution of
undesirable free solid silica particles due to the fast rate of
formation of silica as observed in figure 3d. PS templates
were found to be inadequate to capture all silica nanopar-
ticles on the surface [38].
TGA analysis was conducted to determine the thermal
stability of the synthesized nanoparticles. TGA curves for PS,
sulphonated PS, silica-coated sulphonated PS andHCSNs are
represented in figure 4. Weight loss observed at lower tem-
peratures below 100�C was due to the evaporation of water
absorbed on the surface of the particle [39]. Initial loss in
weightwas found to bemaximum in case ofHCSNs due to the
entrapment ofmoisture on surface pores. Sulphonated PS and
silica-coated sulphonated PS displayed a quick drop at
*340�C and no weight loss was observed above 550�C.Thus, the absence of any remnant sulphonated PS particles
along with silica was confirmed at higher temperatures
([550�C). Twenty-eight per cent of silica residuewas presentafter 550�C, when silica-coated sulphonated PS was ther-
mally decomposed. TGA graph of silica did not show any
decomposition after 100�C which confirmed the absence of
any polymer residue in the HCSNs (figure 4).
N2 adsorption/desorption studies were performed on
HCSNs with varied shell thicknesses (Ts1, Ts2 and Ts3) as
shown in figure 5. The N2 adsorption/desorption isotherms
displayed a type-IV curve, indicating mesoporous nature of
the shell with hollow internal cavity [40–42]. Hysteresis was
noticed at the relative pressure range from0.4 to 1 for samples
Ts1, Ts2 and Ts3 (figure 5). The nature of hysteresis loop
agreed with H4 type as observed from the BET isotherms
[43]. The average pore sizes were determined by using BJH
method and found to vary from 1.55 to 3.4 nm with increase
in shell thickness from 20 to 60 nm (table 2). Specific surface
area of HCSNs was found to reduce from 644.1 to 197.8 m2
g-1 with increase in shell thickness of silica from 20 to 60 nm
(table 2). When the concentration of TEOS was increased,
the thickness of the silica shell increased while more number
of silica particles deposited on the shell quickly. Thus, a rapid
condensation of silica particles on the surface occurred. It
may lead to the formation of a less rigid network of silica
particles with a higher pore size of 3.4 nm.
The surface of the sulphonated PS template was nega-
tively charged due to the presence of sulphonic acid group
confirmed by FTIR analysis (figure 1). The surface of sul-
phonated PS was coated employing cationic surfactant
CTAB by electrostatic force. CTAB acted as a major
ingredient in the formation of HCSNs. Self-assembly of
TEOS on sulphonated PS was guided by CTAB. Further,
Figure 1. FTIR spectra of (a) PS, (b) sulphonated PS, (c) silica-coated sulphonated PS, (d) HCSNs, (e) HCSNs chemical structure [36],
(f) sulphonated PS chemical structure [32].
213 Page 4 of 9 Bull Mater Sci (2020) 43:213
TEOS was allowed to hydrolyse in the basic condition
forming siliceous micelles with negative charge. Calcina-
tion of silica-coated sulphonated PS leads to the formation
of HCSNs and complete removal of polymer template. A
higher thickness of silica shell was achieved while sul-
phonated PS template was used [13,16].
3.2 DOX loading and release studies
The promising application of HCSNs as a drug-delivery
vector was investigated by using DOX as the drug. Loading
capacity and encapsulation efficiency were determined
according to the literature [44]. The loading capacities of
samples Ts1, Ts2 and Ts3 were calculated according to the
equation (1) and were found to be 1.31, 1.11 and 1.06 wt%,
respectively. Since the core sizes of HCSNs were nearly the
same, similar values of loading capacities were observed.
Encapsulation efficiencies were determined for samples
Ts1, Ts2 and Ts3 and were found to be 45.4, 39.1 and 37.4
wt%, respectively. The decrease in encapsulation efficien-
cies of samples Ts1, Ts2 and Ts3 could be due to the
reduction in specific surface area of samples from 644.1 to
197.8 m2 g-1 [45]. The reduction in specific surface area
could be due to the reduction in number of surface pores
with increase in the thickness of the silica shell when sul-
phonated PS was used as the template.
The cumulative DOX release plot of HCSNs samples
synthesized using PS template and sulphonated PS template
are shown in figure 6 at pH 6 and 7.4. The drug release
mechanism for rigid mesoporous systems were noted to be
diffusion controlled [46]. Initial burst release of drug upon
contact with PBS was highest for sample with lowest
Figure 2. SEM images of (a) PS, (b) sulphonated PS. Particle-size distribution from dynamic light scattering (c) PS, (d) sulphonatedPS.
Table 1. Zeta potential analysis of PS and sulphonated PS.
Sample
Zeta potential
(mV)
Standard
deviation
Conductivity
(mS cm-1)
PS -53.3 0.43 0.064
Sulphonated
PS
-65.0 1.6 0.088
Bull Mater Sci (2020) 43:213 Page 5 of 9 213
thickness 20 nm (Ts1). However sample Ts3 with the highest
thickness showed minimum burst release than the other
samples [47]. The rapid release of drug occurred during initial
15 min and accounted for discharge of drug particles present
on the surface and pore entrance ofHCSNs [48].After 1 h, the
percentage cumulative release ofDOX reached 49.1, 43.8 and
35.2% for samples Ts1, Ts2 and Ts3 (at pH 7.4), respectively.
It was observed that the sample Ts1 exhibited the highest
rate of DOX release and sample Ts3 exhibited the lowest
rate of DOX release. Influence of average specific surface
area of HCSNs and thickness of the silica shell on the drug
release rate was the prominent reason behind variation in
the DOX release for HCSNs samples (Ts1, Ts2 and Ts3).
Sample Ts1 with the highest specific surface area and lowest
thickness (table 2) had shorter mesopore length which
caused the rapid release of DOX. However, reduced release
rate was observed for sample Ts3, which had the lowest
Figure 3. TEM images of HCSNs synthesized by varying PS/TEOS ratio (a) 1:1, (b) 2:3, (c) 4:7, (d) 1:2.
Figure 4. TGA plot of PS, sulphonated PS, silica-coated
sulphonated PS, HCSNs.
213 Page 6 of 9 Bull Mater Sci (2020) 43:213
specific surface area and highest thickness (table 2)
[28,42,45]. Further, steady release of drug was observed for
300 min as shown in figure 6. HCSNs samples synthesized
using PS template were found to have lower thickness
(15–30 nm), hence showed steady release up to 200 min as
reported earlier [28]. However, sample Ts3 achieved greater
delay in the initial burst and steady release of DOX for
prolonged time compared to other samples.
pH of the drug release medium is considered to be one of
the important parameters which affect the release of drug
from the carrier [49]. pH of the cancer cell was found to be
lower than the normal cells. Effect of pH of phosphate
buffer was studied for HCSNs samples (Ts1, Ts2 and Ts3)
by maintaining pH of the release medium at 6 and 7.4. It
was found that at higher pH of 7.4, drug release was
comparatively less (30.5% in 15 min for Ts3). It could be
the result of poor solubility of drug at higher pH. At lower
pH of 6, higher release of drug (40.7% in 15 min for Ts3)
was observed. The drug release followed similar trend at pH
6 and 7.4 as shown in the plot (figure 6). The quantity of
drug released at pH 6 was found to be higher than that at pH
7.4 [42].
Figure 5. N2 adsorption/desorption isotherm and pore-size distribution for sample (a) Ts1, (b) Ts2, (c) Ts3.
Table 2. Variation of specific surface area and pore size with thickness of silica shell.
Sample PS/TEOS ratio Shell thickness (nm) Average pore diameter (nm) Specific surface area (m2 g-1)
Ts1 1:1 20 1.55 644.1
Ts2 2:3 40 2.78 391.5
Ts3 4:7 60 3.40 197.8
Bull Mater Sci (2020) 43:213 Page 7 of 9 213
3.3 In-vitro cytotoxicity studies
The in-vitro cytotoxicity studies were conducted on lung
adenocarcinoma (A549) cells by MTT assay method to
assess the possible usage of HCSNs in targeted drug-
delivery systems. Figure 7 shows the results of cytotoxicity
studies for HCSNs, DOX-loaded HCSNs and DOX. Death
of cancer cells was found to increase with the increase in
concentration of DOX-loaded HCSNs. Thus, the percentage
of viable cells reduced from 60.2 to 13.9% as the concen-
tration of HCSNs was increased from 25 to 200 lg ml-1 as
shown in figure 7. The cytotoxicity assays of blank HCSNs
were conducted as control in the concentration range from
25 to 200 lg ml-1. The results confirmed that HCSNs did
not cause any toxicity at lower concentrations [42,50]. The
viability of A549 cells at higher concentration of HCSNs
(200 lg ml-1) was found to be high at about 96% and
demonstrated the good biocompatibility.
4. Conclusions
HCSNs of particle size *160 nm were successfully
synthesized using sulphonated PS as the sacrificial tem-
plate. Sulphonation of PS has modified the negative
charge on the surface of PS from -53.3 to -65 mV.
Thickness of silica shell was tailored from 20 to 60 nm
by altering the concentration of TEOS in PS/TEOS ratio
from 1:1 to 4:7. HCSNs synthesized with sulphonated PS
template showed higher thickness than those synthesized
using PS template due to the enhanced surface charge of
the sulphonated PS template. Hence, dependence of
thickness of silica shell on the surface charge of the
template was obvious. Specific surface area of HCSNs
decreased remarkably from 644.1 to 197.8 m2 g-1, with
increase in the thickness of the silica shell. The delay in
DOX release about 300 min was achieved by monitoring
key properties of HCSNs like shell thickness, specific
surface area and average pore size (1.55–3.4 nm). In-vitrocytotoxicity studies also mark them suitable for the
application in targeted drug delivery.
Acknowledgements
We acknowledge the funding was provided by Council of
Scientific and Industrial Research, India (Grant No. 22/646/
13/EMR-II).
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