• No results found

Sacrificial sulphonated polystyrene template-assisted synthesis of mesoporous hollow core-shell silica nanoparticles for drug-delivery application

N/A
N/A
Protected

Academic year: 2022

Share "Sacrificial sulphonated polystyrene template-assisted synthesis of mesoporous hollow core-shell silica nanoparticles for drug-delivery application"

Copied!
9
0
0

Loading.... (view fulltext now)

Full text

(1)

Sacrificial sulphonated polystyrene template-assisted synthesis of mesoporous hollow core-shell silica nanoparticles for

drug-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 m2g-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-vitrocytotoxicity 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 https://doi.org/10.1007/s12034-020-02209-0

(2)

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.

2.2bSynthesis 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-1to 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 Na2HPO4and 1.8 mmol of KH2PO4in water using a 1 L volumetric flask. PB buffer at pH 6 is prepared by mixing 95 ml of 0.1 M KH2PO4and 5 ml of 0.1 M Na2HPO4 in water using 1 L volumetric flask.

2.2dIn-vitro cytotoxicity assays: Thein-vitrocytotoxicity 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°C with 5% CO2in 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 200lg ml-1. MTT assay reagent was added and incubated at 37°C for 4 h, after 48 h of post incubation

(3)

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

G2ð Þ ¼s I tð Þ I tð þsÞ; ð1Þ where G2(s) is the autocorrelation function, I(t) represents scattering light intensity and sis 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 figure1. 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-1are attributed to vibrations of benzene ring (C–C) of PS [29,30] (figure1a). Sulphonation of PS is confirmed by the occurrence of a strong absorption band at 1170 cm-1 (figure1b) corresponding to the sulphonic group (–SO3H) [13,31]. Figure1f shows the chemical

structure of sulphonated PS according to Mulijaniet al[32].

In figure1c, 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-1belong 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 figure1e [36]. Si–OH bonds face towards the surface of the shell.

SEM images of PS and sulphonated PS are displayed in the figure2a 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 (figure2c 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 table1.

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- ure3. Silica nanoparticles exhibited a structure containing hollow internal core and thick shell confirmed by the TEM images (figure3a–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 (figure3a–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.

(4)

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 figure3d. 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 and HCSNs are represented in figure4. 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 weight was found to be maximum in case of HCSNs due to the entrapment of moisture 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 residue was present after 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 (figure4).

N2 adsorption/desorption studies were performed on HCSNs with varied shell thicknesses (Ts1, Ts2and Ts3) as shown in figure5. The N2adsorption/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 from 0.4 to 1 for samples Ts1, Ts2 and Ts3(figure5). 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 (table2). Specific surface area of HCSNs was found to reduce from 644.1 to 197.8 m2 g-1with increase in shell thickness of silica from 20 to 60 nm (table2). 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].

(5)

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, Ts2and Ts3were 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, Ts2and Ts3and 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 m2g-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) sulphonated PS.

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

(6)

thickness 20 nm (Ts1). However sample Ts3with 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 of HCSNs [48]. After 1 h, the percentage cumulative release of DOX reached 49.1, 43.8 and 35.2% for samples Ts1, Ts2and Ts3(at pH 7.4), respectively.

It was observed that the sample Ts1exhibited 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 Ts1with the highest specific surface area and lowest thickness (table2) 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.

(7)

specific surface area and highest thickness (table2) [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 Ts3achieved 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, Ts2and 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 (figure6). The quantity of drug released at pH 6 was found to be higher than that at pH 7.4 [42].

Figure 5. N2adsorption/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 (m2g-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

(8)

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 7shows 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 200lg ml-1as shown in figure 7. The cytotoxicity assays of blank HCSNs were conducted as control in the concentration range from 25 to 200lg 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 (200lg 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 m2g-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-vitro cytotoxicity 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).

References

[1] She X, Chen L, Velleman L, Li C, Zhu H, He C et al 2015J. Colloid Interface Sci.445151

[2] Beltran-Osuna A A and Perilla J E 2016J. Sol–Gel Sci.

Technol.77480

[3] Chen S, Hu J, Wang F and Liu H 2018J. Dispersion Sci.

Technol.391

[4] Huh S, Wiench J W, Yoo J, Pruski M and Lin V S 2003 Chem. Mater.154247

[5] Vetrivel S, Chen C T and Kao H M 2010New J. Chem.34 2109

[6] Gharibe S, Afshar S and Vafayi L 2011African J. Pharmacy Pharmacol.52265

[7] Holzapfel V, Musyanovych A, Landfester K, Lorenz M R and Maila V 2005Macromol. Chem. Phys.2062440 [8] Yang Y, Chu Y, Yang F and Zhang Y 2005Mater. Chem.

Phys.92164

[9] Covolan V L, Mei I and Rossi C L 1997 Polym. Adv.

Technol.844 Figure 6. Cumulative release of DOX from HCSNs of varying

thickness synthesized using sulphonated PS template (Ts1, Ts2and Ts3) at pH 6, 7.4.

Figure 7. In-vitrocytotoxicity studies on HCSNs (Ts2).

(9)

[10] Wei Y, Wang W, Jin D, Yang D and Tartakovskaya L 1996J. Appl. Polym. Sci.641893

[11] Lin S H, Lai S M, Lin C M, Chou C W and Lee C H 2016J. Polym. Res.231

[12] Zhang X, Zhang L and Yang Q 2014J. Mater. Chem. A2 7546

[13] Liu C, Ge C, Wang A, Yin H, Ren M, Zhang Yet al2011 Korean J. Chem. Eng.281458

[14] Stober W, Fink A and Bohn E 1968J. Colloid Interface Sci.

2662

[15] Nguyen A T, Park C W and Kim S H 2014 Bull. Korean Chem. Soc.35173

[16] Ge C, Zhang D, Wang A, Yin H, Ren M, Liu Y et al 2009J. Phys. Chem. Solids701432

[17] Venkatathri N 2007Bull. Mater. Sci.30615

[18] Yang J, Lind J U and Trogler W C 2008Chem. Mater.202875 [19] Zhang Q, Ge J, Goebl J, Hu Y, Lu Z and Yin Y 2009Nano

Res.2583

[20] Ma S, Wang Y and Zhu Y 2011J. Porous Mater.18233 [21] Moorthy M S, Bharathiraja S, Manivasagan P, Oh Y, Jang B,

Phan T T Vet al2017J. Porous Mater.251

[22] Allen T M and Cullis P R 2013Adv. Drug Delivery Rev.65 36

[23] Kumar S, Poonia N, Madaan K, Lather V and Pandita D 2014J. Pharm. Bioallied Sci.6139

[24] Bianco A, Kostarelos K and Prato M 2005 Curr. Opin.

Chem. Biol.9674

[25] Zeng L, An L and Wu X 2011J. Drug Deliv.20111 [26] He Q and Shi J 2011J. Mater. Chem.215845

[27] Kwon S, Singh R K, Perez R A, Abou Neel E A, Kim H-W and Chrzanowski W 2013J. Tissue Eng.41

[28] Deepika D and Ponnanettiyappan J 2018J. Nanoparticle Res.201

[29] Zhang W H, Fan X D, Tian W and Fan W W 2012eXPRESS Polym. Lett.6532

[30] Ding X, Yu K, Jiang Y, Hari B, Zhang H and Wang Z 2004 Mater. Lett.58361

[31] Yang Y, Chu Y, Zhang Y, Yang F and Liu J 2006J. Solid State Chem.179470

[32] Mulijani S, Dahlan K and Wulanawati A 2014Int. J. Mater.

Mech. Manuf.236

[33] Liu C, Yin H B, Wang A L, Wu Z A, Wu G, Jiang Tet al 2012Trans. Nonferrous Met. Soc. China221161

[34] Varga N, Benko M, Sebok D, Bohus G, Janova´k L and Dekany I 2015Microporous Mesoporous Mater.213134 [35] Nandiyanto A B D, Kim S G, Iskandar F and Okuyama K

2009Microporous Mesoporous Mater.120447

[36] Shin K, Kim J J and Suh K D 2010J. Colloid Interface Sci.

350581

[37] Chen Z, Niu D, Li Y and Shi J 2013RSC Adv.36767 [38] Deng Z, Wu L, Chen M, Zhou S and You B 2006Langmuir

226403

[39] Zou H, Wu S and Shen J 2008Langmuir2410453 [40] Zhou X, Cheng X, Feng W, Qiu K, Chen L, Nie Wet al2014

Dalton Trans.4311834

[41] Li M, Zhang C, Yang X L and Xu H B 2013RSC Adv. 3 16304

[42] Jiao Y, Guo J, Shen S, Chang B, Zhang Y, Jiang X et al 2012J. Mater. Chem.2217636

[43] Thommes M, Kaneko K, Neimark A V, Olivier J P, Reinoso F R, Rouquerol Jet al2015Pure Appl. Chem.871 [44] Zhang Y, Zhi Z, Jiang T, Zhang J, Wang Z and Wang S

2010J. Controlled Release145257

[45] Toni M E A, Khan A, Abbas I M, Puzon L J, Badr G, Al- Hoshan Met al2012J. Colloid Interface Sci.37883 [46] Maria G, Berger D, Nastase S and Luta I 2012Microporous

Mesoporous Mater.14925

[47] Bouchoucha M, Cote M F, Gaudreault C R, Fortin M A and Kleitz F 2016Chem. Mater.284243

[48] Ayad M M, Salahuddin N A, El-Nasr A A and Torad N L 2016Microporous Mesoporous Mater.229166

[49] Mhlanga N and Ray S S 2015 Int. J. Biol. Macromol. 72 1301

[50] Li L 2010ACS Nano.46874

References

Related documents

Since the number density of the bigger sized particles to be present at the interface are less they behave comparatively hydrophilic (higher surface tension) than

The structure of the resulted antimicrobial agent (HST) was characterized, and the antibacterial activities were tested. The results indicated that HS has high loading capacity and

The mesoporous silica shell was synthesized over MWCNTs and SWCNTs using the modified Stöber, surfactant-assisted self-assembly method at room temperature under basic con-

In this research, to employ core–shell nanoparticle as sens- ing probe [28], we developed a DNA-functionalized Si@SiO 2 core–shell nanoparticles-based optical sensor, employing it

More specifically, TiO 2 , CdS, and ZnS were considered as the host materials and Ag as the dopant to form single, core/shell, hollow, and hollow bi-layer NPs

Figure 12: (a) TEM image of CuO-CdSe nanoparticles decorated core-shell heterostructure, (b) HRTEM of CuO-CdSe nanoparticles decorated core- shell heterostructure,

Aqueous solution containing spherical silver nanoparticles of 20–80 nm size have been generated using a newly developed novel electro-exploding wire (EEW) tech- nique where thin

1. Experimentally synthesized ZnO and ZnO@Ag nanoparticles showed characteristic nano rod and hybrid core-shell nanorod appearance respectively. All the experimental