# Sol-Gel Silica Nanoparticles in Medicine: A Natural Choice. Design, Synthesis and Products
## 3 Silica NP Design
### NPs Synthesis Methodologies
#### 3.3.4 Template Syntheses  
Template synthesis is dedicated to the production of mesoporous materials, topic out of the scope of this short review. A very short summary of synthesis process is presented. The seminal work conducted by researchers at the Mobil Oil Corporation in the early 1990s on the synthesis of mesoporous silicates has led to a number of syntheses in which surfactants are used as templates [152]. Ordered mesoporous materials are unique materials that are defined by an ordered and repetitive mesostructured of pores and disordered arrangement at the atomic level. Their synthesis is based on the use of surfactants that act as templates to direct the morphology of the final amorphous material. Simply, the synthesis process  
Figure 10: Examples of sol-gel NPs core-shells possibilities (from left-to-right, up-to-bottom): hollow-spheres (core, core-shell and hollow sphere); nanostructure mesoporous spheres; LIPOSIL structure; SPION-core-silica-shell and ORMOSIL NPs.  
starts with the dissolution of surfactant molecules into polar solvents to yield liquid crystal suspensions. The pair surfactant/solvent defines the working phase diagram. When the surfactant concentration is above the critical micellar concentration (CMC) then the surfactant molecules self-assembly into micelles. Higher surfactant concentrations allow the formation of micellar cubic, hexagonal or lamellar self-assembly structures. Once the (liquid crystal) aggregates are formed, the silica precursors are added to the suspension, the sol-gel reactions occurs and a mesoporous silica material is produced. Finally, the surfactant is removed by chemical or thermal degradation [29] (Figure 11).  
A definite breakthrough in drug delivery was the use of mesoporous silica NPs to host drugs/therapeutic-molecules/markers. A correct selection of the mesoporous design depends on the molecule to be hosted, and is the first criterion used. The most used mesoporous silica NPs in drug or bioencapsulation are MCM-41 and SBA-15. The synthesis of MCM-41 (from the Mobil Composition of Matter series) involves liquid crystal templating commonly cetyl trimethylammonium bromide (CTAB) that lead to a 2D hexagonal pore channel array with 3.6 nm in size. The diameters of MCM-41 NPs can be controlled in a size range from 25 nm to 100-150 nm. The SBA-15 (Santa Barbara type) is also largely used as biocarrier. This type of mesoporous silica material is prepared by cooperative self-assembly with a pluronic P123 (a non-ionic block co-polymer). The channels adopt also a 2D hexagonal packing with a diameter varying from 6 to 10 nm depending on the synthesis conditions.  
The release of the drug from the host mesoporous NP is definitely the big challenge. This may occur through diffusion all through the pore channels (in passive drug delivery) or released under specific stimuli as pH, temperature, ultra-sons or light (in stimuli-responsive systems). Although an impressive variety of mesoporous NPs have design, synthesized and (in vitro and in vivo) tested no products have reached the market so far.