Drug delivery system composed of mesoporous silica and hollow mesoporous silica nanospheres for chemotherapeutic drug delivery
Graphical abstract
Introduction
Controlled and site specific delivery along with zero premature releases are the essential conditions for a drug delivery system of chemotherapeutic drugs ((e.g. Taxol, Doxorubicin, Camptothecin etc.) as they are very toxic to the healthy cells [1]. To achieve this goal several drug delivery systems (liposomes, polymer capsules, hydrogels, nanogels, nanoparticles etc) have been discovered in the last few decades and already been approved by FDA [2,3]. Recently, mesostructured materials have attracted the scientists due to their various interesting properties including high surface area, porous structure, tunable pore size, thermal stability etc. for the loading and delivery of chemotherapeutics in a controlled manner under external stimuli [[4], [5], [6]].
The last few years have witnessed tremendous development in the design and synthesis of hollow and micro/nanostructured materials and their application in various fields [7,8].Among various hollow and micro/mesostructured materials mesoporous silica nanoparticles (MSN) [9]gained substantial attention from chemists and biologists because of their low toxicity, high biocompatibility, uniform mesopores, easy drug loading, high loading capacity, and ability to release the encapsulated guest under different external stimuli [[10], [11], [12], [13]].Due to theenormous applications of MSN, various synthetic routes have been discovered during the last few years for the synthesis of mesoporous silica with different morphologies and controllable pore size [[14], [15], [16], [17]]. Out of all methodologies two traditionally and most widely used preparation methods of MSN are soft template and hard template methods [18,19].
In case of soft template method; templating agents such as vesicles, emulsion (e.g. oil in water, air in water), polymer micelles are used [[20], [21], [22]].This method involves some complex chemical steps. It is difficult to maintain the uniform size distribution, shell thickness, core size, of the prepared MSN due to the low stability and poor uniformity of the soft templates in solution [[20], [21], [22]].To overcome these problems, another approach was developed which is known as hard templating methods [[23], [24], [25]]. In this case, a sacrificial hard template is used. Mesoporous silica is formed around the template followed by removal of the core. Generally inorganic or polymeric beads are used as sacrificial templates in this method. Although this method can produce MSN but it is difficult to prepare the sacrificial template. The removal of the template is also multistep procedure and need more time [[23], [24], [25]].
Although various procedures have been developed throughout the years for the etching of the template core, selective etching of the template core remains one of the favorite methods to the chemist [26]. In this method, a specific portion is selectively etched by the application of acidic/basic solution or by calcinations [26]. Recently, cationic surfactant assisted selective etching using cetyltrimethyl ammonium bromide (CTAB) have been developed by Zheng and co-workers to prepare MSN [27]. Besides hard template and soft template approaches, there are some other methods by which mesoporous silica can be prepared. A wet chemical based route was developed by Yu and coworkers to prepare hollow silica spheres [28]. RuisongGuo and co-workers have prepared hollow mesoporous silica using a cationic surfactant cetyltrimethylammonium chloride (CTAC) [29]. Hollow mesoporous silica spheres were also prepared under hydrothermal treatment using acidic conditions by Wang and coworkers [30].A sol-gel route followed by distillation-precipitation polymerization was employed to prepare a core shell anatasetitania/hollow silica spheres where hollow silica spheres were shell and anatasetitania act as a core [31].A one pot synthetic route was also applied by Binyang Du and coworkers [32]to prepare hollow silica spheres using thermo responsive polymer.
Although several routes have been discovered through several years by various groups but still new routes which will be more straightforward, more economical and easily scalable to the industrial level so that it can be employed for practical application are necessary for the synthesis of MSN and HMSN.
Keeping all these in mind, herein, we report a straightforward and a simple procedure for the synthesis of mesoporous silica and hollow mesoporous silica from mesoporous iron silicate via selective etching of the core under acidic conditions (Scheme 1). Recently mesoporous zinc silicate has been prepared by Kangtaek Lee and co-workers [33] by using well known layer by layer technology. We adopted this methodology with slight modification [33].First, we prepared iron silicate and a simple acid treatment etched iron oxide selectively and produced mesoporous silica (MSN). The size of the synthesized mesoporous silica was around 200 nm with pore diameter of 3.6–4.2 nm. Then we coated this iron silicate by iron oxide followed by silica using a layer by layer (LbL) technique [34].Due to the wide range of material choice, simple methodology, versatility, LbL method becomes one of the prominent technology for coating [[35], [36], [37], [38]]. After the coating, hollow mesoporous silicananospheres (HMSN) were prepared by acid treatment which selectively etched iron oxide. The size of the hollow mesoporous silica was 200–300 nm with pore diameter of 3.6–4.6 nm. We explored these as delivery system of a prominent anticancer drug doxorubicin which is one kind of anthracyclin antibiotic extensively used for the treatment of solid tumors, breast, prostate, uterus, ovary, stomach, and liver tumors [39].We have shown the release of the drug from MSN and HMSNunder external stimuli (pH).
We have also studied the cytotoxicity and cellular uptake of the prepared MSN and HMSN. It has been found that MSNand HMSN, prepared by this method shows good biocompatibility and can release the drug over a period of 4 h. Overall this manuscript describes a new facile method to prepare mesoporous silica and hollow mesoporous silica and their application in chemotherapeutic delivery. We hope this study will help further in the future development of preparation of MSN and HMS and their application as drug delivery vehicles.
Section snippets
Materials
Doxorubicin (DOX), iron acetate, cetyltrimethylammonium chloride (CTAC), tetraethylorthosilicate (TEOS), sodium dihydrogen phosphate, disodium hydrogen phosphate, ethanol, were purchased from Sigma-Aldrich. All the chemicals were used without further purification. Deionized (DI) water obtained from a Millipore water (18 MO·cm) purification system was used for all the experiments.
MFS
We used iron acetate as a metal source and followed a literature procedure with modification for the rest of the
SEM analysis of the prepared compounds
The particle size, morphology and the size distribution were analyzed by SEM measurements. Fig. 1(a &b) shows the SEM images of MFS and CMFS. It is revealed from the images that both MFS and CMFS particles are well dispersed and the morphology of the particles are almost spherical. The size of the particles varies from 200 to 300 nm. Fig. 1 (c & d) shows SEM images of MSN and HMSN. It can be seen that the size of the particles are around 200 nm and the particles are well dispersed with
Conclusion
For the past few years, mesoporous silica has shown various applications in different fields of science. And day by day new synthetic methodology is emerging for the synthesis of these mesoporous materials. In this paper, we reported a simple methodology for the preparation of mesoporoussilica (MSN) and hollow mesoporous silicananospheres (HMSN). First we prepared mesoporous iron silicate and then we coated this iron silicate with iron oxide and silica using layer by layer technique. We have
Conflicts of interest
The authors declare no conflict of interest.
Notes
The authors declare no competing financial interest.
Acknowledgement
The authors would like to thank SIC, IIT Indore for providing all the facility and infrastructure. We are grateful to the Powder X-ray diffraction (P-XRD), Facility equipped at Sophisticated Instrument Centre (SIC), IIT Indore. We are grateful to the BET facility quipped at Sophisticated Instrument Centre (SIC), IIT Indore. C. Adhikari A. Mishra acknowledges financial support from IIT Indore.
References (49)
- et al.
In-vitro evaluation of sol-gel processed spray dried silica gel microspheres as Carrier in controlled drug delivery
Int. J. Pharm.
(2000) - et al.
Drug-loaded polyelectrolyte microcapsules for sustained targeting of cancer cells
Adv. Drug Deliv. Rev.
(2011) - et al.
A simple approach to prepare monodispersemesoporous silica nanospheres with adjustable sizes
J. Colloid Interface Sci.
(2012) - et al.
Calorimetric investigation of metal ion adsorption on 3- glycidoxypropyltrimethylsiloxane + propane-1,3-diamine immobilized on silica gel
Thermochim. Acta
(2005) - et al.
Attachment of 2-aminomethyl-pyridine molecule onto grafted silica gel surface and its ability in chelating cations
Polyhedron
(2004) - et al.
Ligand-decorated nanogels: fast one-pot synthesis and cellular targeting
Biomacromolecules
(2012) - et al.
Encapsulation of water-insoluble drugs in polymer capsules prepared using mesoporous silica templates for intracellular drug delivery
Adv. Mater.
(2010) - et al.
Engineering inorganic nanoemulsions/nanoliposomes by fluoride-silica chemistry for efficient delivery/Co-delivery of hydrophobic agents
Adv. Funct. Mater.
(2012) - et al.
Synthesis of single crystal hollow silver nanoparticles in a fast reaction-diffusion
Chem. Mater.
(2011) From Microporous to mesoporous molecular sieve materials and their use in catalysis
Chem. Rev.
(1997)
Nanoengineering of inorganic and hybrid hollow spheres by colloidal templating
Science
Metal nanostructures with hollow interiors
Adv. Mater.
Advances in microporous and mesoporous solids—highlights of recent progress
Adv. Mater.
Tailor-made polyelectrolyte microcapsules: from multilayers to smart containers
Angew. Chem. Int. Ed.
Preparation of novel hollow mesoporous silica spheres and their sustained-release property
Nanotechnology
Permeable silica shell through surface-protected etching
Nano Lett.
Precise tuning of porosity and surface functionality in Au@SiO2 nanoreactors for high catalytic efficiency
Chem. Mater.
Micrometer-sized mesoporous silica spheres grown under static conditions
Chem. Mater.
Room temperature growth of mesoporous silica fibers: a new high-surface- area optical waveguide
Adv. Mater.
Hollow spheres of Mesoporous Aluminosilicate with a three-dimensional pore network and extraordinarily high hydrothermal stability
Nano Lett.
Organic functionalization and morphology control of MesoporousSilicas via a Co-condensation synthesis method
Chem. Mater.
Electrostatic self-assembly of silica Nanoparticle−Polyelectrolyte multilayers on polystyrene latex particles
J. Am. Chem. Soc.
Hollow micro-/nanostructures: synthesis and applications
Adv. Mater.
A facile route to hollow nanospheres of mesoporous silica with tunable size
Chem. Commun.
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