In today’s world, nanoparticles are playing a key role in making this world a better place by serving in different fields and industries through various means and sources. Aluminum oxide is a compound comprising aluminum and oxygen where its formula is known and written as Al2O3.

The entire chemical compound has diversity in its nature and possesses remarkable properties and characteristics which enable its production and applicability at a large scale. The prominent and most significantly used applications of aluminum oxide can be seen in the field of biomedical as they are being used in this field for quite a long time and benefiting this area of science immensely.

Introduction

The improved characteristics of nanoparticles are the reason for them being utilized so much in industry and research than the bulk materials. Ultrafine particles of smaller sizes than 100 nm fabricates nanoparticles. The effects are because of its small size as a good amount of atoms are exposed on the surface when they are made from the nanoparticles. When they are made from a nanoscale, significant changes come in the behavior and performance of the materials. When they are composited from nanoparticles, enhancements are made, for instance, enhanced thermal conductivity, enhanced electrical conductivity, and enhanced strength and hardness.

Aluminum Oxide

Al2O3 is the chemical formula of Aluminum oxide, which is oxygen and aluminum’s chemical compound. Aluminum oxide is known as Aluminum (III) oxide and it occurs the most out of various other aluminum oxides. Commonly, it is known as alumina and can be identified as alundum, aloxite, or aloxide depending on certain applications or forms. Aluminum oxide is important for producing aluminum metal, as a refractory material because of its high melting point and as an abrasive because of its hardness.

Properties of Aluminum Oxide Nanoparticles

Nanosized aluminum oxide, also known as nanosized alumina, comes in the spherical form or the form of closely spherical nanoparticles, and oriented form or undirected fibers. Despite have spherical morphology, aluminum oxide nanoparticles look like white powder. They are graded as an irritant and highly flammable in both solid and liquid forms as they can be the factor in serious respiratory and eye irritation.

Properties of nanoscale colloidal alumina particles

Their fibers and particles are of a small diameter which is 2-10 nm. They have more than 100m2/g specific surface area. High defectiveness of the nanoparticles’ specific structure and material surface. Following are included in the nanoparticle’s specific structure and there is a possibility of modification in them; surface composition, structure, phase composition, degree of crystallinity, and pores’ size and volume.

Properties of the nanoscale fibers of aluminum oxide

20,000,000:1 is their length-diameter ratio. Their fibers are highly oriented. The fibers have a weak interaction among themselves. There are no surface pores in it. They have a high surface concentration of the hydroxyl groups

Physiochemical properties

The dimensions and size of the nanoparticles heavily determine the nanoparticle's physiochemical characteristics. When the size changes, there comes a difference in the atomic arrangement too in the nanoparticles. According to reports, nanoparticles have 3 distinctive layers and they are not pointed objects. The surface layer is the outermost and first layer. The surface layer is made up of metal ions or molecules and they are the reason for the functioning of the nanoparticle's surface eventually. The shell layer is the 2nd layer and it is very different from the first and the third layer. The nanoparticle's core is the last and third layer and it represents the nanoparticle's basic chemical formula itself.

Structure determination

Thermal, magnetic, mechanical, optical, and electrical characteristics come in the general physicochemical properties. The energy levels and electrons determine the electric conductance, emission, and absorption, making optical and electronic characteristics symbiotic. Emission and spectra of absorbance are displayed by the nanoparticles. Nanoparticles' capillary force, friction, adhesion, elastic modulus, hardness, and other mechanical characteristics are studied for facilitating these particles’ usage in the industry. When it comes to synthesizing wear resistance products, scientists use improved hardness. Long-lasting lubricants are designed by using low friction, and adhesion is used for the particle removal processes.

Thermal properties

Nanoparticle’s thermal characteristics are determined by the kind of metal that makes up the nanoparticles. In comparison with most non-metallic compounds’ fluids or solids, a higher thermal conductivity is possessed by oxides of aluminum and metals like copper. When nanoparticles are added to these metal oxides and metals, it enables the fluid to have an enhanced thermal conductivity whereas it was a bad thermal conductor before.

Manufacturing process

Laser ablation, hydrothermal, sputtering, pyrolysis, sol-gel, and ball milling are among the many techniques that can be used to synthesize Aluminum oxide nanoparticles. However, the most commonly utilized method for the production of nanoparticles is laser ablation as it can be made in liquid, vacuum, or gas. Laser ablation offers many benefits in comparison with other techniques like high and rapid purity processes.

Moreover, one can easily collect the nanoparticles that are made through the laser ablation of materials in liquids as compared to the nanoparticles that are made through the laser ablation of materials in the gas state. A way was recently found by Max-Planck-Institut für Kohlenforschung, a chemist in Mülheim an der Ruhr for producing corundum (alpha-alumina), alumina’s extremely stable variant, in nanoparticle’s form by utilizing the simple mechanical method in a ball mill.

Derivation of aluminum oxide

Recycled alumina and bauxite mineral are the two main sources of aluminum oxide. However, bauxite mineral, aluminum's ore is the main significant source of aluminum oxide. Instead of being a mineral, Bauxite mineral is a sedimentary rock, made up of a mixture of aluminum compounds with other nonmetals, metals, and their oxides like quartz (SiO2), magnetite (Fe3O4), and hematite (Fe 2O3). Brazil, Jamaica, China, and Australia are bauxite’s biggest manufacturers. Alumina has one small natural source but due to its frequent characterization as a gem and because of its characteristics of reflection and light absorption in the visible range when it is mixed with transition metals, it leads to a beautiful and colorful crystal.

Recycling of virgin aluminum

One of the other easy methods to obtain aluminum oxide is to recycle virgin aluminum. Due to aluminum oxide's characteristics of hardness and durability, one can't see the existence of the dissimilarities in functionality and characteristics of the virgin Aluminum and its recycled counterparts. In recycling, energy is utilized in a very small amount and unrecyclable Aluminum oxide’s amount is 10%, which is very low and it makes this particular source an extremely fascinating one particularly for industries like the construction industry as they utilize aluminum oxide in huge amount. Sufficient aluminum oxide is provided by these 2 sources to the world but better techniques might be used for our planet’s sustainability as mining is included.

Bayer process

When the bauxite mineral is obtained, then the Bayer process is used for crushing it and then purifying it to Aluminum. Just moments after sodium hydroxide’s hot solution is used to wash the bauxite mineral, aluminum is produced, and then aluminum oxide is obtained. The obtained aluminum hydroxide later gets calcinated to alumina. Rarely corundum or obtained alumina bulk is used to develop alumina nanoparticles. Laser ablation is the preferred method for the production of nanoparticles because of its versatility in nanoparticle size and the different media. The used nanoparticles are mostly pure. On interaction with the solid, the laser beam produces a plasma and evaporates to molecules and their clusters.

Formation of fumes

A fume is produced by the evaporated particles and it is expanding with time. On further expanding, it interacts in the setup with an ambient gas or a different fluid that meets with it for forming alumina nanoparticles. X-ray diffraction (XRD), transmission electron microscopy (TEM), and emission spectroscopy were then used to analyze the nanoparticles for characterizing the collected type of nanoparticles.

Applications of Aluminum Oxide Nanoparticles

Drug delivery

Aluminum nanoparticles have been utilized in ordered mesoporous aluminum oxide’s form to enhance Telmisartan’s oral delivery as a poor-water soluble compound. Telmisartan is an anti-blood pressure drug. Evaporation induced self-assembly method synthesized ordered mesoporous aluminum oxide. X-ray diffraction (XRD), scanning electron microscopy, and Fourier transforms infrared then characterized it and then its pores were loaded with Telmisartan through the usage of a solvent impregnation method. Loading efficiency of 45% was seen between the nanoparticles and the drug in results. Moreover, when ordered mesoporous aluminum oxide was being loaded, it led to the release of Telmisartan and its major dissolution.

Aluminum oxide-ibuprofen nanocomposite’s sol-gel was fabricated in another study for increasing ibuprofen’s bioavailability. This was the reason for the fabrication of nano-aluminum oxide by aluminum oxide alkoxide’s controlled hydrolysis, followed by loading of the nano-aluminum oxide particles with the ibuprofen that’s insoluble in water. Then, Thermogravimetric analysis, Fourier transform Raman spectroscopy, Emmett and Teller method, Brunauer, UV-Vis spectrophotometry, and XRD analysis was used to characterize the prepared nanocomposite.

Effect on solubility

In sol-gel nanocomposite’s form with the aluminum oxide, there was a major increase in ibuprofen’s solubility and controlled release. The main mechanism and reason behind these significant increases is some of the characteristics of the sol-gel nano-aluminum oxide’s surface for instance high density of hydroxyl groups, highly porous structure, and high surface area. In this study, the major revelation is of the suitability of the nano-aluminum oxide particle of this type as an efficient and effective drug delivery vehicle.

Biosensing

There have been recent reports on the usage of aluminum nanoparticles as novel platforms to detect various molecules. Aluminum oxide nanoparticles are utilized for sensing bovine serum albumin. Self-assembled anodic aluminum oxide modified LSPR (localized surface plasmon resonance) sensor's surface for performing the biosensing. In self-assembled anodic aluminum oxide, a well-organized aluminum oxide nanohole structure was produced on an LSPR chip. Nanocarbon-modified aluminum oxide nanocrystal’s shell/core was utilized in another study for sensing the DNA in a competitive bioassay. Easy surface engineering was enabled by this carbon layer and that’s why it was utilized as a platform for increasing aluminum oxide nanocrystal’s surface reactivity, biocompatibility, and stability.

Florescent nature of aluminum oxide

Aluminum oxide nanostructures and their fluorescent nature was implemented for various detection purposes like in vitro DNA detection, intracellular cargo monitoring, and cell imaging, for the purpose of them being used in biosensing applications. Moreover, there have been reports that aluminum nanoparticles have the ability of sensing chemicals. Just like this feature, aluminum oxide nanoparticles are also utilized with chitosan for detecting phenolic molecules as a nanocomposite. Aluminum nanoparticles were decorated on a chitosan film and then fabricated nanocomposite was loaded with horseradish peroxidase (HRP).

Cancer therapy

A modified pulse anodization process was used to fabricate aluminum oxide nanomaterial in the nanotubes’ form containing Thapsigarin, they were then loaded with Thapsigarin. An autophagy inhibitor, 3-methyladenine co-administered Thapsigarin for targeting autophagy signaling in both the normal and the cancerous cells. Aluminum oxide nanotube loaded with Thapsigarin displayed no cytotoxic effect in the normal cells however in the cancer cells, it induces autophagy signaling, referring to the ability of the aluminum oxide nanotubes for anti-cancer therapy as a new generation of the drug delivery vehicle. There have been reports on the anti-cancer characteristics of the spherical nano-aluminum oxide particles other than their suitability for cancer therapy. Rajan Y.C. et al. fabricated poly-glutamic acid-modified aluminum nanoparticles in this study and implemented them as cytotoxic agents for inducing the death of the cell in the prostate cancer cells. Aluminum nanoparticles displayed cell toxicity towards the treatment of PC-3 prostate cancer cells.

Surface potential and viability

In another study, increased surface zeta-potential was shown by the nano-petal AlNPs-treated mouse neuroblastoma Neuro-2a cells towards the negative values along with decreased viability. The shape of the utilized aluminum oxide nanostructures determines the zeta potential's value and cell viability's percentage. Cell toxicity of the highest level was showed by nano-petal aluminum oxide, followed by wedge-like nanoparticles and nanoplates. Aluminum nanoparticles showed the highest change in cell surface’s zeta potential.

AINPs are also utilized as an adjuvant in cancer immunotherapy in vivo and in vitro as an enhanced cancer treatment strategy in which aluminum nanoparticles were utilized as a cancer antigen carrier to dendritic cells’ autophagosomes, effectively presenting the delivered antigens to the T-cells. AlNPs applications lead to a major increase in the amount of the activated T-cells, resulting in provoking a significant cancer remission and potent anti-tumor activity of these cells. Moreover, it is proved in this study that when it comes to boosting cancer vaccines’ efficacy, the potential candidate is AINPs.

Anti-microbial effects

Aluminum nanoparticles exhibit strong antimicrobial activities due to their large surface area. Sadiq M. et al. proved aluminum nanoparticle’s anti-Escherichia coli (E. coli) property in his study, in which bacterium E. coli incubated 179 nm-sized-AlNPs of different concentrations. Scientists observed a mild anti-growth effect because of the electrostatic interaction between the bacterial cells and the nanoparticles. Moreover, a small decrease was seen in the bacterium's extracellular protein content. In another study, aluminum nanoparticles displayed anti-growth effects which were originated from nanoparticle's direct attachment to these bacterial cell walls.

Aluminum oxide as a silver nanocomposite

When utilized in aluminum oxide–silver nanocomposite’s form, great antimicrobial characteristics are shown by the aluminum oxide nanomaterials against Staphylococcus epidermis (S.epidermidis) and E.coli, which refers to the nano-aluminum oxide’s potential biomedical applications as the composite structures.

There was another research in which aluminum oxide nano-coatings, in the form of aluminum oxide core/Fe3O4/shell magnetic nanoparticles, displayed remarkable magnetically-derived photothermal killing effects on various drug-resistance, gram-positive and gram-negative bacterial isolates. The aluminum oxide shell is a recognizer of bacterial cells in this intelligently designed nanocomposite. Although, the Fe3O4 core subsequently kills the bacterial cells photothermally. In addition, a magnetic field is used to use the core Fe3O4 for guiding the nanoparticles towards the bacterial cells.

Treatment of other diseases

Vasoactive intestinal peptide conjugated Alpha-Aluminum nanoparticles and was utilized as anti-asthmatic nano-drugs for preventing the mouse model from getting allergic asthma. The vasoactive intestinal peptide was protected against enzymatic degradation in the asthmatic mouse model's lung by using alpha-aluminum nanoparticles, and they displayed a strong anti-asthmatic activity than the non-conjugated vasoactive intestinal peptide and beclomethasone.

Nano-thrombolytic system has been used to explain AINPs' potential advantages. AINPs sol-gel form was loaded with the thrombolytic enzyme streptokinase for showcasing this potential. When they have a size of less than 500 nm, an efficient and effective thrombolytic activity was seen on various samples by prepared streptokinase-aluminum nanoparticles along with streptokinase's sustained release.

Bimolecular preservation and stabilization

According to Volodina V.K. et al’s study, protein molecules can be correctly folded by the aluminum nanoparticles and they can be the nano platform for that. Aluminum nanoparticles interact with the denatured negatively charged proteins electrostatically for being utilized as a renaturing material. They also prevent the misfolding and aggregation of the denatured negatively charged proteins. Until the un/misfolded protein folds correctly, the refolding process is kept under control by the aluminum nanoparticles in addition to the reaction.

Immunotherapy

A major target of next-generation vaccines and immunotherapy is autophagy induction because of autophagy’s central role in presenting the antigens to the T lymphocytes. AINPs have been researched as an autophagy inducer because of this reason. Cysteine peptidase A and B were conjugated in one study to Aluminum nanoparticles and they were utilized as leishmania vaccine for inducing autophagy in the macrophages. When these nanoparticles were administered, fast internalization is shown of the conjugated nanoparticles by leishmania-infected macrophages. Aluminum nanoparticles can also be used to design an anti-HIV vaccine as they are effective and efficient nano-adjuvants to provoke mucosal and systematic immunity. A peptomer was covalently conjugated onto the aluminum nanoparticles, leading to a nanoconjugate of 300 nm that can cause a strong immunologic reaction in mucus.

Pharmaceuticals

The nanoparticles are still being utilized for drug delivery purposes in various fields of medicine. Dosage's accuracy determines the nanoparticle's power in delivering the drugs into the body and they can release it in very certain locations at a set time in the body, which leads to fewer side effects as the drugs' therapeutic efficiency will increase. Fewer side effects will be caused as compared to the number of side effects that will be caused if current methods are used for the delivery of the drug.

Alumina nanoparticles are a good option for IV delivery of the drug into body parts because of their durability. The durability of the nanoparticle matters here as such body parts has extremely low pH, making it easy to degrade the nanomaterials before nanomaterials reach their desired location. The most concerning thing right now is aluminum toxicity as recently people have been linking cancer and aluminum. However until now, aluminum has shown no carcinogenic effect so that link has not been proven, still one should take care while adding aluminum nanoparticles for delivery of the drug.

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Advantages of Aluminum Oxide Nanoparticles

AINPs are attractive and efficient nanomaterials because of a number of their great characteristics. Some of them are mentioned below:

(i) Due to having known methods of manufacture, they are easily available.

(ii)They can be easily conjugated with molecules of other origins like biological and chemical molecules because of their vast surface area.

(iii) AINPs can interact easily with biological interfaces, enabling them to be utilized for biological purposes.

(iv) In harsh, complicated non-biological environments and other numerous conditions, AINPs are stable enough for being utilized.

(v) They are ideal nanomaterial when it comes to developing various nanomaterials because of the fact that their surface functionalization protocols are very clear.

Conclusion

Aluminum oxide nanoparticles have gained popularity and prominence in the field of biomedical specifically as they are serving this field for a long time. This enables these nanoparticles to fight and combat a series of deadly diseases as well which is a huge achievement for such tiny particles. Their excellent nature in which they are present and then molded into the form that can be used for beneficial purposes is a very hard and tiring process but once achieved can work wonders for the industries as well as the humans. 

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References:

https://www.azonano.com/article.aspx?ArticleID=3318

https://www.researchgate.net/publication/326480862_Biomedical_applications_of_aluminium_oxide_nanoparticles

https://www.sciencedirect.com/science/article/abs/pii/S0927775717309494

https://cutt.ly/2SPRueO