Drug molecules are generally insoluble, making it difficult to deliver them to the diseased tissues. In this regard, mesoporous silica has become a promising drug carrier.
Surface Modifications
Mesoporous silica possesses extraordinary properties that make it an excellent material for nano-catalysis, nano-fabrication and especially for drug delivery. These unique features include large surface area, tunable pores with diameters in the range of micropores (less than 2 nm), mesopores (2-50 nm) and macropores (greater than 50 nm).
Mesoporous silicon is a promising drug delivery system that offers superior biocompatibility. There are two basic synthetic strategies to functionalize MSNs; co-condensation and post-synthetic grafting. Co-condensation involves introducing organic functional groups during mesoporous silica synthesis. After condensation, the resulting MSNs can be functionalized by ion-exchange with an acidic solvent such as ammonium nitrate or hydrochloric acid [103]. This technique allows for the formation of functional groups on the inner mesopore walls and exterior particle surfaces.
Another useful way to modify mesoporous silica is through dielectric barrier discharge plasma. This method allows for uniform surface modification in a cost-effective and environmentally friendly manner.
The results showed that adsorption of rifampin was dependent on the size of the molecule and the type of functional groups. The MSNs fabricated with TMPAC exhibited the highest rifampin load, which was probably due to the high specific surface area of these MSNs.
Drug Loading
The mesoporous structure of the synthesized MSNs allows for high drug loading capacity. This loading is a surface-related phenomenon and mainly depends on the total surface area, pore size and pore shape. These grafting techniques allow for a controlled modification of the MSNs morphology and porosity as well as their surfaces [141].
A number of factors affect the mesopore diameter of MSN materials, including the synthesis conditions (pH, temperature, reaction time), silica precursor, catalyst concentration, and experimental conditions such as reaction conditions. The mesopore size of the MSNs can also be adjusted by chemical treatment of the silica precursor with different surfactants and additives [142].
The presence of surfactants during the mesoporous chemistry can be disadvantageous for biomedical applications. This is because the common surfactants such as CTAB can interact with the phospholipids of the cell membrane and induce cell death at high concentrations.
Mesoporous silica nanoparticles are capable of enhancing the solubility and dispersibility of poorly water-soluble drugs, as well as delivering hydrophilic active agents. The tunable pore volume, morphology and surface of MSNs facilitate their functionalization with a wide range of molecules, including DNA or siRNA [145].
This is because the mesoporous matrix provides a large surface area for binding and dispersing these large-size molecules, thereby enabling them to be delivered to targeted cells in vivo [146].
For example, Wang et al. prepared dendritic mesoporous silica nanoparticles with a range of pore sizes to load the antibiotic rifampin, which is effective against Mycobacterium tuberculosis, in an ex vivo small intestine infection model. They found that rifampin loaded inside MSNs displayed improved antibacterial activity as compared to free lysozyme.
Targeted Drug Delivery
The physico-chemical properties of mesoporous silica have made it a promising drug delivery carrier. Silica nanocarriers exhibit a high loading capacity (especially for biologically active molecules), mechanical stability and tunable drug release mechanisms in response to internal and external stimuli.
In this method, the mesoporous silica consists of a hollow interior surrounded by a dense microporous shell or coating. A good example is a multifunctional MSN platform for the combinational therapy of cancer, which contains doxorubicin loaded into mesopores by physical absorption, and tumor-targeted fusion peptide and therapeutic peptide conjugated with 2,3-dimethylmaleic anhydride bound to the MSNs through disulfide bridges [187].
In terms of drug delivery, mesoporous silica offers several advantages over organic nanocarriers, such as their low cytotoxicity and large surface area. In particular, the tunable mesopore diameters allow for selective adsorption of drug molecules by controlling the size of the confined mesoporous matrix. This feature enables the tuning of MSN drug release rates in response to internal and external stimuli.
Biocompatibility
Mesoporous silica is characterized by its high surface area and pore volume, tunable mesopore dimensions and shapes, well-ordered structure, chemically accessible surfaces for surface modification, easy synthesis and handling, hydrolytic degradability under biologically relevant conditions with the formation of biocompatible degradation products, and excellent biocompatibility [1].
The polycation augments the binding capacity of the MSNs with nucleic acids, allowing adsorption and subsequent release of siRNA in vivo. The results showed that the silencing efficiency increased with increasing concentration of rifampin delivered by PEI-captured MSNs.
