CP0254 Developing Research Methods I

Question:

Write about Silica Nanoparticles as Drug Delivery Systems.

b. Biocompatibility & Toxicology

Answer:

Scientists have praised mesoporous silica as a breakthrough in the field nanotechnology, with huge potentials for healthcare.

Scientists have carried out extensive research on mesoporous Silica. They have discovered their benefits in catalysis as also in drug delivery and imaging.

These particles exhibit a variety of characteristics, such as high specific area, tunable porous structures, high pore volumes, and also high physiochemical stability (1).

These properties were previously used by researchers to create hydrophilic and/or hydrophobic active substances.

In a variety of experiments, researchers have recently discovered that these agents possess surface functionalization and PEGylation.

These features led scientists to believe they can be used extensively for drug delivery in different treatment options for cancer patients.

Solgel method can be used for the preparation of silica nanoparticles.

Hydrolysis is the first step.

Next, they are mixed with head groups surfactants.

The interaction between the surfactant a silica precursor will change depending on its nature.

This interaction results in hydrogen bonding and electrostatic force, which can vary depending on the surfactant used.

The hydrophilic or lipophilic balance with span 20 span 40 span 60 is 8.6, 6.7, 4.3 in the respective order.

The value of pH (2) is the main determinant of the silica pre-cursor and surfactants’ interaction.

This, in turn, is shown to have an impact on the overall morphology.

It is shown that the surfactant of one particular charge and an oppositely charged precursor create strong interactions, resulting in ordered particles of silica.

When hydrogen bonds are formed between non-ionic surfactants and charged silica precursors, neutral conditions result in a longer duration.

Researchers have discovered that silica nanoparticles can be prepared by using span 60 in the Bet method. This means that the specific surface area is approximately 11,000.500 m2/Kg, and the particle size is about 80nm.

Below is a micrograph showing that nanoparticles are smaller when the chain length of surfactant is increased.

Nanoparticles can be made between 150 and 80 nm by using span 20 or span 40 in the non ionic surfactant categories.

You can alter the size of the span series non-ionic suprafactant, but you cannot change the order.

The ordering and size can be modified by using non-ionic surfactants such as Brij 65.

Specific surface area (SSA), of silica particles synthesized with different surfactants.

The ph of the reactions affects how small the nano particles will be.

It all depends on the amount of ammonia. The higher the concentration, the smaller the particle size.

Particle size can increase with an increase of the ph. This affects the rate at which monomer addition takes place. Polymerization is also affected by the pH.

Condensed species that are ionized at a pH of around 7 become mutually repellent.

The solubility and size of silica increases above ph 7, which is why particles appear to be increasing in size.

You can also see that the number of particles decreases when highly soluble small particles are dissolved and then re-precipitate on longer, less soluble particles.

This is Ostwald Ripening.

Stobers’ method is another process that may be used in one- or two-step processes.

Here is the precursor of silica known as the tetraethyl Orthosilicate, (Si(OEt).

4, TEOS), is subject to hydrolisis reaction with alcohol in alcohol similar to that of ethanol or methanol, in the presence ammonia (3).

Ammonia is used as a catalyst.

These reactions produce ethanol and a mixture ethoxysilols.

You may also experience further reactions, which can result in the loss of water or alcohol.

Cross linking is achieved by further condensation following further hydrolysis.

This results in granular silica whose diameters range from 50 to 2000nm.

Similar steps are followed in the second step, where hydrochloric acids is used as the catalyst to replace ammonia.

Bio-Compatibility With Silica Nanoparticles

Silica nanoparticles serve as a vehicle for drug delivery. It is therefore important to check their safety in blood.

Their biocompatibility must be tested as they are directly in contact with tissues and cells.

Researchers took silica powdered particles as part of an experimental study.

During the experiment, PBS was actually used to fill all the hydrophilic mesoporous MSNs and MSNsRhB channels.

When the plasma was mixed with them, there was no room left that could absorb additional water.

They had no effect whatsoever on the plasma’s anticoagulation and coagulation functions.

They were therefore found to be hemo-compatible.

They also easily enter cells and don’t affect cell survival.

They are compatible with many other drugs and have been used as biosensors.

This has been beneficial for imaging as well as gene capabilities.

The scientists discovered that these cells are internalized in primary cortical neurons cells.

It was quite surprising to observe that they did NOT cause cell death in vitro and in vivo.

They also proved to be very useful because they could bind, transport, and then release DNA into cells. This is what makes them so useful in transfecting NIH-3T3 and SH-SY5Y human neuroblastoma cell lines (4).

It was also proved that silica nanoparticles can be used in conjunction with cells.

Lu et al. published a paper that demonstrated promising results in biocompatibility in 2010.

The two-month study in mice showed that the drug had a negligible effect on the non-target organs. In addition, it was highly effective in delivering cancer drugs to the target organs.

Camptothecin-loaded MSNs can accumulate in tumors, releasing the drugs.

They can also be released by urine.

The mice excreted 95% to 90% of the silica nanoparticles.

Fu et.al. in 2013 also supported this claim (6).

Their future potential for drug delivery was demonstrated by this.

Researches revealed that silica particles are low in toxicity when they are exposed to moderate doses.

They are therefore extensively used in biosensors that measure glucose, hypoxanthine levels as well as l-glutamate, lactate, and hypoxanthine levels.

They are also biomarkers used in the identification of leukemia cells.

This can be achieved by optical microscopy imaging, DNA delivery or drug delivery as well as cancer therapy (7).

There have been cases where these nanoparticles tended to agglomerate, causing protein aggregation if administered in vitro in 25 mg/mL.

Researchers attempted to identify the root cause and concluded that oxidative stresses is responsible for the cytotoxic effects in vivo as well as in vitro.

They have identified three main reasons for the cell’s cytotoxic effects: increased lipid peroxidation and decreased cellular glutathione.

However, scientists have stated that these nanoparticles can be used in low doses to avoid cytotoxicity.

This is because these nanoparticles have a limited ability to cause cytotoxicity when they are extremely large (9).

They also depend upon the cell type they are administered to.

Kim et.

In 2015, the researchers Kim and colleagues found that Monodisperse silica nanoparticles in spherical form (SNPs), when given in moderate amounts, induce endocytosis. But at higher doses, they cause cell death (10).

It is necessary to do more experiments to find the optimal doses of the particles and which cell types they cause negative effects.

The above discussions revealed that silica particles are essential for drug delivery in health care. They also serve as biosensors and gene carriers.

Their high biocompatibility has been established.

But there are some toxicity risks that could be increased if they are used improperly, in high doses, in large sizes or on unknown cell types.

To ensure safe use, researchers and healthcare professionals must be aware of the characteristics of nanoparticles.

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