Synthesis of porous silica hollow spheres using sacrificial template for drug delivery applications

Article history: Received January 22, 2014 Received in revised form February 02, 2014 Accepted 8 May 2014 Available online 30 May 2014 In this work, we report on the synthesis of SiO2 hollow spheres using carbon nanospheres as the sacrificial template by hydrothermal method. The synthesized substrates are in a spherical morphology and uniform size distribution. The effects of hydrothermal process, concentration and the reaction temperature were optimized during synthesis of carbon nanospheres. Infrared spectroscopy (IR), and scanning electronic microscopy (SEM) methods were used for identification of the synthesized products. The synthesized SiO2 nanospheres were used as drug carrier to investigate in vitro release behavior of monoterpenic phenol isomers, carvacrol and thymol, in simulated body fluid (SBF). Ultraviolet-visible spectroscopy (UV-vis) method was carried out to determine the amount of the drugs entrapped in the carrier. The results indicated that SiO2 nanospheres have high ability to adsorb the drugs and there is no need for adjusting the pH during the adsorption process. The drug release profile shows a three stages pattern and indicates a delayed release action. © 2014 Growing Science Ltd. All rights reserved.


Introduction
Morphology of nanostructures plays an important role in determining their properties.Because of low density, high surface area, loading ability, encapsulation of guest molecules, high porosity, ease of production, and suitable biodegradability, hollow nanospheres are of great interest 1, 2 .Performance of SiO 2 nanospheres is strongly influenced by the size of their porosity and their surface area.SiO 2 nanospheres have many applications in medical sciences 3 , biotechnology photovoltaic chromatography 4,5 and targeted drug delivery 6 .So far, many physical and chemical methods were used to synthesis the SiO 2 nanospheres, such as hydrolysis 7 , hydrothermal, sol gel, polymerization 8 , using sacrificial templates 9 , and etc.Among these, sacrificial templates method has attracted much attentions due to its ability to control particle size 10 .By controlling template size and concentration, reaction time and temperature, desired morphology and size of SiO 2 nanospheres could be obtained 11 .In this research, SiO 2 nanospheres with uniform morphology and size distribution were synthesized using carbon sacrificial templates.In addition, the effects of temperature, concentration and reaction time were optimized.To create porosity in SiO 2 nanospheres, cetyltrimethylammonium bromide (CTAB) was used as surfactant.Exploring of drug loading on porous SiO 2 nanospheres showed that these particles have good potential to be a drug carrier with no need to pH adjustment.

Materials and Methods
All the reagents were of analytical grade and were from Merck Company.Reagents were used without any further purification.
The FT-IR spectra were recorded using KBr disks on an FT-IR SHIMADZU 8400S infrared spectrometer and absorptions were reported as wave numbers ( cm -1 ).Ultraviolet-visible (UV-Vis) absorption spectrum was measured on a T80 spectrophotometer.The morphologies of particles were observed by scanning electron microscopy (SEM, LEO-1455 VP).50 mL of glucose solution (0.4 M) was transferred into an autoclave receptacle and maintained at 180 °C for 12 h.The product was dispersed in water using ultrasonic bath, then centrifuged for 20 min at a speed of 6000 rpm, and finally washed with ethanol.The procedure of dispersing, centrifuging and washing repeated six more times.After solvent evaporation, carbon nanospheres were obtained.
To synthesize the SiO 2 hollow spheres, 0.06 g carbon nanospheres were dispersed in 100 mL ethanol, and 0.05 g CTAB was added to the mixture.The pH was adjusted at 10.5 by addition of 10 mL ammonia solution (25%).Then, while using an ultrasonic bath, 2 mL of tetraethylorthosilicate (TEOS) was added dropwise to the suspension.After 1h sonication, the product was centrifuged and washed with water and ethanol until pH 7 and let to dry.The obtained precipitate (C@SiO 2 ) was calcined at 600 °C for 3h to burn the carbon cores and obtain the SiO 2 hollow nanospheres as final product.
The loading of the monoterpenic phenol isomers (carvacrol and thymol) was carried out by the soaking of 0.01 g of SiO 2 hollow spheres in 5 ml ethanolic solution of drugs (6.5 mM).The suspension was stirred for 48h.After centrifugation of drug-loaded SiO 2 nanospheres, the amount of the drug loaded was measured using the absorption intensity of the drug remained in solution at 420 nm by means of UV-vis spectroscopy method.In addition, the in vitro release of the drug was performed by soaking the drug-loaded powder in simulated body fluid (SBF), with continuous stirring at 37 • C in a water bath.The release ration of the drug from the carrier into the solution was measured by examining the concentration of the drug in SBF at different time intervals, by means of UV-vis spectroscopy.

Results and discussion
IR spectrum of carbon nanospheres shows that they contain carboxyl, ester and alcoholic functional groups on their surface.According to IR spectrum, the peaks at 875-750 cm -1 , 1460-1000 cm -1 , 1715-1700 cm -1 , 3000-2815 cm -1 and 3700-3000 cm -1 region are attributed to the out of plane aromatic C-H, C-O stretching, ester stretching, aliphatic C-H stretching, and carboxylic acid stretching vibrations, respectively.Comparing Fig. 1, a and b shows that with increasing the hydrothermal time (from 8 to 16h), glucose loses more water and finally polymerizes.Therefore by reducing the oxygen to carbon ratio, the intensity of the 3700-3000 cm -1 peaks are reduced 13 .As shown in IR spectra of glucose core and SiO 2 shell before and after calcination (Fig. 2), the functional groups attached to the carbon nanospheres are eliminated that could be due to the complete burning of carbon template.The peaks at 470 and 1110 cm -1 region are attributed to the Si-O bending and stretching vibrations, respectively.The peak around 3500 cm -1 could be due to the O-H stretching vibration of water.EM images Fig 3 a -d

Conclusi
In summ sacrificial te uniform mo process con of SiO 2 can delivery.Th during adso rates.

Fig
Fig. 1.IR Sp and (b) after