Question:


Write about Silica Nanoparticles and Drug Delivery Systems.a. Preparation/formulation

b. Biocompatibility/toxicity

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Answer to Question: CP0254 Developing Research Methods I

Scientists view mesoporous silica as a relatively recent innovation in the field. It has many potential uses in healthcare.

Researchers have extended their research into mesoporous Silica. They have shown a positive role in catalysis and in drug delivery and imaging.

They have a wide range of properties, including high specificities, tunable structure, high pore volume, and physiochemical instability (1).

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

Researchers discovered new features in the compounds through a range of experiments. It has been shown that they have surface functionalization and can be PEGylated.

These characteristics led scientists to believe that these can be extensively used for drug delivery purposes in various cancer treatments.Formulation:

Solgel methods can be used to make silica nanoparticles.

The first step is hydrolysis.

The surfactants are then added to the mixture.

Depending on the nature of the surfactant being used, the interaction between the surfactant (and the silica pre-cursor) will change.

This interaction is characterized by the formation of hydrogen bonding or electrostatic forces.

The hydrophilic-lipophilic balance with span 20, 40, 60 and 60 are respectively 8.6, 6.7, 4.3 and 4.3.

The value of pH (2) determines the amount of interaction between the silica-precursor and surfactants.

This is what affects the overall structure of the articles.

In basic conditions, it is observed that the surfactant containing a particular charge forms strong interaction with the precursor of an oppositely charged charge. This results in ordered silica particle.

The duration of the hydrogen bonds formed between charged silica pre-cursors and non-ionic suprafactants under neutral conditions is longer.

Multiple researchers discovered that silica particles can be made with span 60, which is used in Bet to prepare them. Their specific surface was approximately 11,000.5 m2/Kg.

As you can see, the surfactant’s chain length is increasing which causes a decrease in the size of the nanoparticles.

Nanoparticles of sizes between 150 nm and 80 nm can easily be produced by using span 20, span 40 or span 60, which are non-ionic surfactants.

The span series of non ionic sufactants can be modified in size, but not in order.

But, you can change both the size as well as the ordering by using non-ionic suprafactants like Brij65.

Specific surface area (SSA), for silica nanoparticles, synthesized using different surfactants.

The ph systems of the reactions also influence the size of nanoparticles.

It depends on how much ammonia is present in the solution. A higher concentration will lead to a smaller particle size.

Particle size will increase as a function of the ph. Also, the rate at which monomer addition occurs and polymerization is affected by the pH.

It is known that condensed substances become ionized when the ph is around 7. This results in them becoming mutually repellent.

As silica’s solubility increases above 7 ph, particles grow in size because of particle aggregation.

A decrease in the number of particles is also observed. Highly soluble small particles undergo dissolution, which then results in re-precipitation for longer less soluble particles.

This is Ostwald maturing.

Stobers process is another method that can be used. It may be done in one or two steps.

Here you will find the precursor of silica (Si(OEt),

4, TEOS), is made to undergo hydrolisis reactions in alcohol just like ethanol and/or methanol with ammonia (3).

This is when ammonia acts as a catalyst.

A mixture of ethoxysilols and ethanol is produced by reactions.

There are further reactions that can occur, leading to the loss or alcohol.

Cross-linking occurs through condensation upon further hydrolysis.

This produces granular silicon with diameters ranging from 50 to 2000nm.

This is the second step of the process. Hydrochloric Acid is used in this stage as a catalyst.Source:

Bio-Compatibility of Silica nanoparticles

Silica nanoparticles are used as a vehicle to deliver drugs and it is vital that we test their safety within our bloodstream.

Because they come in direct contact with cells and tissues, it is crucial to check their biocompatibility.

Researchers collected dry silica particles for an experimental study.

During the experiment all the hydrophilic, mesoporous MSNs were filled with PBS.

They did not have any space that could absorb further water in plasma.

They did not have any effect on the plasma’s coagulation and anticoagulation function.

It was concluded that their hemo-compatibility is satisfactory.

They are easy to enter the cells and do not interfere with cell survival.

Researchers have used them to deliver drugs, as well as as biosensors because of their histocompatibility. Scientists like Bardi et al. (2010), have developed NH2functionalisd CdSe/ZnS quantum dot (QD)-doped SiO2 NPs.

This has enabled both imaging and gene capability.

Scientists found that the primary cortical nerve cells in the brain are responsible for absorbing this information.

It was astonishing to see that the drugs did not cause cell death both in vivo as well as in vitro.

They are also useful due to their ability bind, transport and release DNA in cells. This allows for GFP plasmid transfer ion of NIH-3T3 or human neuroblastomaSH-SY5Y cells (4).

This proved the compatibility of silica particles with cells.Source:

Lu et al. published a paper showing promising results for biocompatibility.

It was administered to mice over a two-month period. It showed a lower effect on non-target organs and a high rate of success in delivering cancer drugs to those organs.

Camptothecin loaded MSNs are extremely capable of accumulating in tumors and releasing drugs.

They also released the drugs through urine.

The mice were able to excrete approximately 95% the silica microparticles.

Fu et.al. (2013), who also studied excretion ability, supports this conclusion (6).

This demonstrated their future effectiveness as drug delivery systems.Toxicity:

Numerous researches proved that silica microparticles can be toxic when they are exposed to low levels.

They are extensively used in biosensors for measuring glucose, hypoxanthine levels (l-glutamate), and lactate.

They are also used to identify leukemia cells using biomarkers.

This can also be done using optical microscopy imaging (OMI), DNA delivery, Drug delivery, and even cancer therapy (7).

Some cases showed that nanoparticles could agglomerate and result in protein accumulation when given in vitro 25 mg/mL.

Researchers attempted to discover the reason for this, and they concluded that oxidative Stress is the main cause.

Three reasons were identified as the main reason for the cytotoxic effects on cells: an increase of lipid peroxidation; a decrease in cellular glutathione and an increase in reactive oxygen species production.

However, scientists have shown that cytotoxicity can still be avoided if these nanoparticles were used in moderate amounts.

The only time these nanoparticles contribute to cytotoxicity is when their dose and size are very high (9).

They depend on the cell type that they are administered.

Kim et.

Kim et.al. discovered that Monodisperse, spherical silica particles (SNPs), resulted when they were introduced in moderate amounts in cells’ endocytosis. Higher doses however resulted a decrease in cell survival (10).

Therefore, more research is required to identify the correct doses and sizes of particles as well as the cell types that they can have adverse effects.Conclusion:

These discussions led to the conclusion that silica microparticles are very important as drug delivery vehicles in healthcare and as biosensors and gene carriers.

Their high biocompatibility level is already known.

The dangers of using the nanoparticles in an inappropriate manner such as high doses, large sizes or on unknown types of cells can increase.

Researchers and healthcare professionals should be cautious, and at the same time be familiar with the properties of the nanoparticles. This will ensure that safe practices are followed.References:

Li Z. Barnes JC. Bosoy A. Stoddart DJF. Zink I.

Biomedical applications: Mesoporous Silica nanoparticles

Chemical Society Reviews. 2012;41(7):2590-605.

Singh LP. Agarwal SK. Bhattacharyya SK. Sharma U. Preparation nanoparticles of silica and their beneficial role in cementitious substances.

Nanomaterials & Nanotechnology

2011 Jan 1, 1:9.Ibrahim IA, Zikry AA, Sharaf MA.

Stober silica.

Journal of American Science. 2010;6(11):985-9.

Bardi G. Malvindi MS, Gherardini LI, Costa M. Pompa PA, Cingolani RO, Pizzorusso TO. The biocompatibility with amino functionalized SiO 2 nanoparticles of primary neural cells and their gene-carrying performance. Biomaterials.

2010 Sep 30;31(25),:6555-66.6

Lu J. Liong M. Li Z. Zink JI. F. Biocompatibility, Biodistribution, Drug?delivery Efficiency of Mesoporous Silica Nanoparticles for Cancer Therapy in Animals. Small.

2010 Aug 16th;6(16).

Fu C. Liu T. Li L. Liu H. Chen D. Tang. The absorption of silica nanoparticles and their toxic effects on mice were determined by using different exposure routes. Biomaterials.

2013 Mar 31.34(10).2565-75.

Tang F. Li L. Chen D. Mesoporous Silica Nanoparticles – Synthesis, biocompatibility, drug delivery.

Advanced Materials.

2012 Mar 22nd;24(12),:1504–34.

Xie GG, Sun J. Zhong GF, Shi L. Zhang D. Biodistribution toxicity of intravenously administered silicon nanoparticles to mice.

Archives of toxicology.

2010 Mar 1st;84(3):183-90He Q, Zhang Z, Gao F, Li Y, Shi J.

In vivo biodistribution of mesoporous Silica nanoparticles and their urinary excretion: effects of particle sizes and PEGylation small.

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

Kim IY. Joachim E. Choi H. Kim K. Toxicity of silica microparticles depends upon their size, dosing, and the cell type.

Nanomedicine: Nanotechnology Biology and Medicine.

2015 Aug 31.11(6).1407-16.

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