CP0254 Developing Research Methods I

Question:

Write about Silica Nanoparticles for Drug Delivery Systems.

b. Biocompatibility, toxicity

Answer:

Scientists consider mesoporous silicon to be a new development in nanotechnology with many potential applications in healthcare.

Scientists have done extensive research on mesoporous silicon and found that they play a beneficial role in catalysis, drug delivery, and imaging.

There are many characteristics of the particles, including high specific areas, high pore volumes, tunable pores structures, high pore volumes, and physiochemical stability (1).

Researchers have used these characteristics in the development of hydrophilic active agents and hydrophobic ones.

Researchers have discovered many new characteristics in these active agents through various experiments. They also possess the ability to PEGylate and surface functionalization.

Scientists believe they could be used extensively as drug delivery vehicles for various types of cancer treatment.

Sol gel can be used to prepare silica nanoparticles.

They are first subject to hydrolysis.

They are then combined with head-groups of surfactants.

The interactions between surfactant, silica precursor and surfactant will vary depending on the type of surfactant.

This interaction can be characterized by hydrogen bonding, electrostatic force or hydrophilic interactions.

The hydrophilic, lipophilic balances with span 20, span 40 and span 60 are 8.6, 7.7 and 4.3 respectively.

The pH (2) value is the most important determinant of the interaction between silica precursors and surfactants.

This affects the overall morphology and structure of the articles.

Basic conditions show that silica particles are formed when the surfactant with a particular charge and its oppositely charged precursor form strong interactions.

In neutral conditions, hydrogen bonds between charged silica precursors or non-ionic surfactants form and lead to a longer time.

Different researchers have found that silica nanoparticles prepared using span 60 had a specific surface area of approximately 11,000.m2/Kg. The particle size was around 80nm.

The micrograph below shows that the surfactant chain length increases, which results in a decrease in particle size.

Nanoparticles with sizes between 150 and 80 nm are possible by using span 20, span 40, or span 60 non-ionic surfactants.

The span series of non-ionic surfactants allows for the modification of the size but not the order.

You can alter both the order and size by using other non-ionic surfactants like Brij 65.

Specific surface area (SSA), silica nanoparticles made using different surfactants and pH.

The ph system of reactions also affects the size of nano particles.

It is dependent on the ammonia concentration. Higher ammonia concentrations will result in a larger particle size.

Particle size is affected by the ph. The rate of monomer and polymer addition increases with an increase in ph.

The ph of 7 is the point at which condensed species become ionized, making them mutually repellible.

Particle aggregation is a phenomenon that causes particles to grow in size above ph 7.

Also, it is seen that particles with a high soluble are smaller and undergo dissolution. The particles then undergo re-precipitation of larger particles.

This is Ostwald ripening.

Stobers’ procedure is another one that can be performed in either a single step or two-step process.

The precursor to silica, the tetraethyl orsilicate (Si(OEt),) is shown here.

4. TEOS) undergoes hydrolisis in alcohol, similar to ethanol and methanol (3).

This is where ammonia acts like a catalyst.

The reactions lead to ethanol, which is then combined with ethoxysilols.

Further reactions can lead to loss of alcohol and water.

Cross linking occurs due to condensation after further hydrolysis.

The result is granular silica having diameters of 50-2000nm.

The second step is similar except that hydrochloric acid is used as a catalyst instead of ammonia.

Bio-Compatibility of Silica Nanoparticles

Silica nanoparticles can be used as a vehicle for drug delivery. Therefore, it is important to test their safety in the blood.

It is essential to test their biocompatibility as they come into direct contact with cells and tissues.

Researchers used silica powder as an experimental material in an experiment.

During the experiment, all hydrophilic mesoporous channels (MSNs) and MSNs -RhB were filled with PBS.

They were completely filled with PBS, so that they could absorb more water from the plasma.

It was discovered that they had no effect on plasma’s coagulation or anticoagulation functions.

Their hemo-compatibility was therefore satisfactory.

They can also be easily absorbed into cells and have no effect on cell survival.

Because of their compatibility, researchers have been able to use them both as biosensors and drug delivery systems.

This has allowed for both imaging and gene abilities.

Scientists discovered that primary cortical neural cell internalize this information.

It was amazing to find that they didn’t cause any cell death in vivo or in vitro.

They were also discovered to be beneficial due to their ability transport, bind and release DNA into cells. This aids in GFP plasmid transfect ion NIH-3T3 as well as human neuroblastoma SHY5Y cell lines (4).

The histocompatibility of silica nanoparticles and cells was therefore established.

Lu et al. published a paper in 2010 that showed promising results for biocompatibility of fluorescently labeled silicon nana particle.

The drug was administered to mice for a period of two months. It had a very low effect on non-target organs, and it delivered the drug well to cancerous target organs.

The extraordinary ability of camptothecin-loaded MSNs to accumulate in tumors and release the drug is remarkable.

They were also discovered to be released via urine.

The mice’s bodies excreted approximately 95% of the silica particles.

Fu et. al. (2013) also confirmed this finding (6).

These results demonstrated their potential to be effective drug delivery in the future.

Extensive researches revealed that silica nanoparticles are low in toxicity when they are exposed to moderate amounts.

They are widely used in biosensors to measure glucose, hypoxanthine levels and l-glutamate.

They can also be used as biomarkers for leukemia cell identification.

This can be achieved using optical microscopy imaging and DNA delivery.

These nanoparticles can agglomerate and cause protein aggregation in vitro when administered at 25 mg/mL.

Researchers tried to determine the cause of this phenomenon and found that oxidative stress is the primary reason.

Three main reasons have been identified: an increase in lipid peroxidation, decreased cellular glutathione levels and increased production of reactive oxygen substances that all contribute to the cells’ cytotoxic effects (8).

However, researchers have found that such nanoparticles can be avoided in moderate doses.

These nanoparticles can contribute to cytotoxicity if they are large in size or very high in dose (9).

They also depend on the type of cell they are given to.

Kim and colleagues conducted an experiment.

In 2015, Kim et al. found that monodisperse spherical silicon nanoparticles (SNPs), when administered in moderate amounts, resulted in endocytosis in the cells. However, higher doses of SNPs caused a decrease in cell viability (10).

More experimentation is needed to determine the appropriate doses and the effects on specific cell types.

Using the above discussion, it was discovered that silica nanoparticles can be used as drug delivery devices in health care as well as acting as gene carriers and biosensors.

It is well-established that silica nanoparticles are biocompatible.

There are certain risks associated with using them in an unsafe manner, such as in large doses or on unspecified cell types.

Researchers and healthcare professionals need to be cautious and educated about the characteristics of nanoparticles in order to practice safe.

Li Z, Barnes JC, Bosoy A. Stoddart JF. Zink JI.

Biomedical applications of nanoparticles made from mesoporous silica.

Chemical Society Reviews.

Singh LP. Agarwal SK. Bhattacharyya SK. Sharma U. Preparation and use of silica nanoparticles in cementitious materials.

Nanomaterials, Nanotechnology.

2011 January 1:9:

Stober silica is used to prepare spherical nanoparticles of silica.

Journal of American Science.

Bardi G. Malvindi MA. Gherardini LS, Costa M., Pompa P., Cingolani RL, Pizzorusso TR. The biocompatibility and gene carrying performance of CdSe/ZnS nanoparticles with primary neuron cells.

2010. Sep 30, 2011;31(25),:6555-66.

Lu J, Liong M., Li Z. Zink JI. Tamanoi F. Biocompatibility and drug?delivery efficacy of mesoporous silicon nanoparticles in cancer therapy in animals.

2010 Aug 16th, 6(16):1794-805

Fu C, Liu T. Li L. Liu H. Chen D. Tang F. Absorption, distribution and excretion of mesoporous silicon nanoparticles in mice exposed to different exposure routes.

2013 Mar 31, 34(10):2565-75.

Tang F, Li L., Chen D. Mesoporous Silica Nanoparticles: Synthesis, Biocompatibility, and Drug Delivery

Advanced Materials.

2012 Mar 22nd, 24(12):1504-4.

Xie G., Sun J., Zhong G. Shi L., Zhang D. Biodistribution of intravenously administered silica particles in mice.

Archives of toxicology.

2010 Mar 1;84(3),183-90

Effects of particle size and PEGylation on in vivo biodistribution, urinary excretion and biodistribution of mesoporous silicon nanoparticles.

2011 Jan 17, 7(2):271-80.

Kim IY, Joachim E. Choi H., Kim K. The toxicity of silica nanoparticles is dependent on their size, dosage, and the type of cell.

Nanomedicine: Nanotechnology in Biology and Medicine.

2015 Aug 31;11(6).1407-16.

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