INTRODUCTION:

Nanotechnology is the science related to both engineering and advancement in technology operated at the nanoscale, which is about 1 to 100 nanometers¹or in other words, one nanometer is 1 billionth or 10^-9of a meter. The origin of the word “nano” comes from the Greek word “dwarf”, meaning small. Though, the world of the nanoscale is small, but it has envisaged enormous potential. To imagine, the diminutiveness of the nanoscale to the meter is to compare the smallness of a marble to the magnanimous earth. History dates back to when, Norio Taniguchi first described the term nanotechnology to describe engineering from the ground level that is from atoms and molecules.

However, the baseline motivation towards the field of nanotechnology probably comes from Richard Feynman for his historical presentation, “There is plenty of room at the bottom” on nanotechnology given by him, in 1959, at the conference of American Physical Society. He pointed out that the building of substances can be done at a very miniature level (molecular level), without physical restrictions.²

Nanotechnology, since its evolvement, has reached onto every sector possible. It has extended from the fields of engineering, information, communication, automobiles to medicine, pharmaceutical research, genomics, and diagnosis and has been increasing to multifold levels day by day. Researchers are continually manipulating small particles like atoms and molecules of an element to develop different possibilities. The various nanoparticles include nanopores, nanotubes, quantum dots, nanoshells, nanospheres, nanowires, nanocapsules, dendrimers, nanorods and liposomes.³

The application of the same principles has led to the development of very efficient dentistry tools concerning diagnosis, prevention and treatment, helping us achieve more significant positive outcome in oral health care. Nano dentistry is a term used for nanotechnology used in dental field. The physical, chemical and biological aspects must be well looked into before the nanomaterial is taken for its usage.⁴Some researchers follow a “top-down” technique, that is, creating small particles out of milling huge blocks or fragmenting an active ingredient to develop small submicron particles for efficient use. Others might follow a “bottom up” pattern, to develop substances from the molecular level. The encapsulation achieved with nanoparticles helps to extend the therapeutic effect by its controlled release, and helps in maximizing the curative effect with its direct contact with the target site.²

Nanoparticles have extensive usage, starting from preventive drugs for oral diseases, treatment of malodour, in prosthesis fabrication to dental implants. The most common nanoparticle used is that of silver, followed by carbon and iron particles. Hydroxyapatite is a natural nanoparticle produced by our body, formed of collagen.⁴ Hence, they are commonly used on the surfaces of the implant body to increase their affinity towards the bone formation. Ergo, operating on such a minute aspect provides a perspective to envision the restoration of a tooth at a level that offers a closer approximation of its individual anatomic structures.⁵

Benefits of Nano dentistry:

Nano dentistry is nothing but futuristic improvisation to what has been followed age long. It uses the same basics of material or medicine at a molecular level, to achieve greater predictability of treatment provided. The various advantages of using Nano dentistry are

1. Stability- The material incorporated has better stability; hence, its shelf life is increased to incredible amounts. In addition, when the same material is either dispensed or used in the oral cavity, its stability against the oral fluid is more.

2. Preparation Techniques- Since, the preparation is at nanolevels, with appropriate armamentarium, it is easy and its large-scale manufacturing is possible.

3. Controlled Release- Corresponding to its function at nanolevels, it makes its way quickly to target site, (especially, dentogingival sac), as carriers or vectors, thus maximizing its therapeutic potency.²

Applications of Nanotechnology in dentistry:

The recent era has seen many developments in dentistry, aiming to improve the reliability, predictability and increasing safety of the procedure. Modern technologies such as nanotechnology, digitalized dentistry, cosmetic dentistry and usage of lasers for daily routine procedures, have helped considerably to diversify treatment methodologies and achieve results at faster pace. Nanotechnology has been applied in various aspects of dentistry. It is envisioned that in the longer term, biomimetic approaches and nanotechnology will be used to repair and rebuild damaged enamel.⁴

Nanobiomaterials in preventive dentistry:

The modern dentistry era is based on a conservative rather than a conventional approach. Nano particles helps us to fulfill this by preventing decay at a very early stage. Dental caries are a result of interactions between the bacterial organism with the tooth surface with diet, time, and host as the interplay. When a tooth surface is subjected to an acidic pH over a long time, it results in the demineralization of the tooth structure, causing dental caries.⁶ For prevention of dental caries, a modification of the biofilm layer over tooth surface has been suggested, which does not wear off and protects the tooth surface over a long period. For example, nanoparticles of graphene because of their planar arrangement into thin sheets are capable of forming resistant biofilm over teeth and hence protect it from corrosive actions. Similarly, silver has antibacterial properties because of its bactericidal effects. Thus, when used in combination with toothpastes, imparts increased oral health. Silica filler particles, when used in combination, also helps in detaching the plaque and bacterial deposition under the influence of forces in the mouth. Hence, they also become a suitable choice for polishing agents. Even, nanoparticles like of, Zirconia oxide are found to have anti-biofilm activity against certain bacteria (such as Enterococcus feacalis and Streptococcus obrinus) and therefore can be successfully used as a polishing agent in dental practices.³But, a clinician should always keep in mind, that these are just an adjunct. The patients are still susceptible to caries if conventional oral health care such as tooth brushing or fluoride application is neglected.²However, there is still ambiguity answering the questions like on the longevity of polishing effect and if the surface eliminates plaque formation.⁷

Nanobiomaterials in restorative dentistry:

The negative effect of amalgam restorations has continuously let us made progress towards alternatives more aesthetic and oral environment friendly, keeping the in mind it being of high strength and durability the same as amalgam. Contemporary nano composites are fabricated with the bottom up approach (the nanoparticles are combined at molecular levels) whereas the microfilled composites are fabricated with top down approach where the active ingredient like ceramics, quartz, and glasses are fragmented to sizes below 100nm.² These materials can offer esthetic and strength advantages over conventional microfilled and hybrid resin based composite systems in terms of smoothness, refinement, the precision of shade characterization, flexural strength and micro hardness.⁵The knowledge of shape and size of the particle, that is, macro, micro and nano filler particles⁸ helps in determining its best use in composite materials. Silica is the most common dental filler used in resin composites. They can be of two forms, nano particle – a single nanoparticle of size 5-25 nm and nanoclusters – a group of nanoparticles, forming larger sized particles. It imparts high strength renders to its size, surface area, biocompatibility, low cytotoxicity, adsorption capacity and low density. Apart from this, zirconia is also one such material, when used as a nanoparticle in conjunction with composites, imparts better efficacy and durability than ceramics because of its commendable strength and high shear capacity. Hydroxyapatite, also, has the property of attaching itself to the natural tooth particles and helping it to repair enamel surfaces. Hence it has been widely used in toothpastes and mouth rinsing solutions to provide a clean oral environment.⁴

Nanoparticles in Prosthodontics:

Apart from the material advances and surface coated implants, nanoparticles are also making their way into denture base resins to enhance their properties. The plaque deposition on denture base resins is a common source of denture stomatitis in daily denture wearers. It has been illustrated that the inclusion of metallic nanoparticles like titanium oxide, ferric oxide and silver to PMMA has reduced the adhesion of plaque to a considerable extent, thereby decreasing the chances of denture stomatitis. The biomolecular adherence is reduced based on increased hydrophobicity due to addition of the metal nanoparticles to PMMA. In addition to this, studies have shown no changes in color stability or mechanical strength by addition of the metal nanoparticles.⁴ For fixed dental prosthesis, like, crowns, bridges, inlays and other dental elements, nanostructured yttrium stabilized zirconium oxide ceramics has been extensively used because of its high strength, durability, and better aesthetics.

Nanoparticles in orthodontics:

In the wake of excessive root resorption caused by orthodontic forces, there is a constant need to make it less harmful. A study done by Katz et al. showed that a surface coating on the wire with inorganic fullerene-like tungsten disulfide nanoparticles (IF-WS2) had decreased the number of frictional forces on the tooth subjected to movement orthodontically. Cao et al in a study also demonstrated the high antimicrobial and bactericidal properties of nitrogen-doped titanium oxide thin film, when coated unto brackets, which helped to prevent demineralization of enamel and gingival orthodontic patients. Incorporation of nanoparticles leads to better mechanical properties, like increase in elastic modulus, decreased surface roughness and better durability. Advancement in nanotechnology also led to the development of nanorobots that directly come in contact with the periodontal tissues and allow fast and painless straightening of tooth, change in positioning and tissue healing within no time.³

Nanotechnology on Dental Implants:

According to GPT 8, a dental implant is a material or device placed in and/or on oral tissues to support an oral prosthesis. Hence not only, it has to be capable of bearing the masticatory stresses, but it also has to integrate with the bone and bio mimic itself as its tooth counterpart. The surface chemistry, topography and wettability has a major role to play to enhance the activities occurring at tissue implant level. Nanobiomaterials have been constantly used in implantology, be it to enhance osseointegration or act as a protective biofilm to counter microbial action.⁸ The newer implant designs use titanium that is coated with a thin layer of hydroxyapatite or iron oxide nanoparticle, which promoted bone growth and helped in osseointegration of the implant with the surrounding bone. More recently, zirconium has also been tried as an agent of implant surface modification.Anodized silicon, titanium, and aluminum are frequently used as nanoporous anodic alumina (NAA), porous silicon (pSi) and Titania nanotubes (TNTs) for development of drug-releasing implants.

Nanoparticles as Dental Drug-Delivery Systems:

Nanotechnology is the new trend in the drug delivery system in the biomedical and pharmacy field.¹⁰They have been suggested as drug-delivery systems for periodontal infection since a long time. Pocket formation causes the destruction of the supporting periodontal tissues causing exfoliation of the teeth. Because of their size, they can be projected onto the target cell with ease. Hence, it a very significant medium of site-specific treatment approach and effectively manage periodontal infection. Comparing local versus systemic drug systems, the local delivery systems would outrun based on site specificity, faster dispersion of the drug, effect for a longer time, and would counteract the adverse effects of systemic drugs. They are usually distributed as gels, strips, films, or fibers, which could be directly inserted into the dentogingival unit and leading to slow release of the drug over 3- 30 days. There have been numerous formulations of polymeric and non-polymeric nanoparticles for local drug delivery over the years. In a study by Elsaka et al., the combination of titanium oxide nanoparticles to a glass-ionomer cement proved enhancement in antibacterial effect. In another study, a combination of minocycline and fluoride proved to be an excellent antibacterial and anticariogenic agent. Liu et al. also suggested using chitosan nanoparticles for local drug delivery system. It inhibited the growth of P. gingivalis and A. actinomycetemcomitans and helped in changing the inflammatory response in human gingival fibroblasts. In the non-polymeric criteria, the charge on the nanoparticle helps to attach the antimicrobial or anti calculus agents to it thereby, prolonging their effect in the oral cavity. Although many developments have been in this context, there is still a need for further research to make this line of treatment a viable option in the future.¹⁰

Nanomaterials as salivary sensors:

Salivary sensors or biosensors is a novel technology, which makes sample collection easy and noninvasive, making them an upcoming and promising choice for diagnosis. The use of nanotechnology as salivary biosensors has been envisioned for a long time now. It is basically a self-sustained device which contains an element (a biologically active element), that when subjected to an environment, detects the amount of chemicals present and relates to it with high specificity, even in the presence of low detection levels. Clark and Lyons developed the first biosensor, which was an enzyme-based glucose sensor, to detect the glucose level in the body to indicate diabetes. Its use ranges from immunoassays for detection of salivary hormones, antibodies, and cancer biomarkers. The various uses of nanotechnology as salivary biosensors are as follows

· In detection of HIV, hepatitis and other viral diseases. The salivary sensors, detect the particular antibody related and hence make diagnosis fast and easy.

· A surface plasmon resonance (SPR) biosensor helps in detecting changes in cortisol levels in saliva. It helps in detection of psychiatric disorders, like depression, schizophrenia, or differing amounts of stress levels, thereby providing an early diagnosis.

· With a wireless mouth guard biosensor, it has been possible to detect uric acid and phosphate levels, which help in detecting obesity in children at an early stage.

· Hormonal changes can also be detected with SPE technology.

· Cardiovascular indicators like, CRP and lactate, can also be detected by salivary biosensors which would help indicating diseases like myocardial infarction and onset of major cardiovascular diseases¹¹.

· Nanotechnology is very popular in field of cancer therapy due to its various advantages.¹²Wei et al was the first to apply the usage of nanotechnology to determine salivary biomarker ( IL-8 and multiplex of other proteins) to detect oral cancer. he early diagnosis of cancer could greatly reduce the mortality rates of the disease.¹³Further, salivary biomarkers are also used to detect breast, lung and pancreatic cancer. This became a significant breakthrough, since nanotechnology made it easy to collect samples, without the apprehension of undergoing biopsy procedure. The OFNASET (Oral fluid Nano sensor test) technology platform combines leading technologies such as self-assembled monolayers, microfluidics, and cyclic enzymatic amplification for detection of cancer. Apart from oral cancer, it can assess for breast, pancreatic, and lung cancers, Type II diabetes, Alzheimer's disease, and Sjogren's syndrome.¹¹.

Following is an overview of the basic nanoparticles and usage in dentistry (as discussed above)

Nanoparticle (major element)	Uses in dentistry
Carbon nanotubes	Cavity restoration
Graphene	As a coating on implants, acrylic teeth (for its action against biofilm)
Hydroxyapatite	Decreases dentinal hypersensitivity, used in toothpastes, mouth rinses For coating on implants- facilitates osseointegration
Iron oxide	Controls microbial infections, used in implants
Zirconia	Crowns, dental implants, nano-composites, polishing agent (active against enterococcus feacalis)
Silica	Fillers particles, polishing agent, for dentinal hypersensitivity
Silver	Antibacterial properties, used in tooth pastes, mouth rinses
Titanium	Drug releasing implants
Biosensors like SPR, Quartz crystal biosensor for ATPase H + transporting, lysosomal accessory protein (ATP6AP1),	For cancer detection. Also, Diabetes, CVS diseases, obesity, sexual hormonal diseases, drug abuse via salivary markers

Hazards of using nanoparticles:

With its numerous advantages, the use of nanoparticles in day-to-day dentistry has some drawbacks. The substantial administration of nanomaterials in dental materials and treatment plan has a potential effect on human cell toxicity.¹³The three most important factors that cause toxicity are the size, charge, and shape of the nanoparticle used. Along with which the mechanism of action, by which it causes damage, involved in cell lysis and cell apoptosis.

The size of the nanoparticle affects the surface chemistry and charge on the constituent particle. The most extensive literature for the toxicity of nanoparticles comes from the inhalation of a particle with a mean diameter of 10μm. The shape of the nanoparticle interferes with macromolecules like the potassium channel, which may further damage the heart by causing an arrhythmia. Also, studies indicate its damage to blood cells, like platelets. It increases its aggregation, thereby leading the clotting of the vessels. The charge on a nanoparticle directly effects its bioavailability and the determines the level of its toxicity. For example, Cationic nanoparticles such as gold and polystyrene can cause hemolysis and blood clotting, whereas anionic nanoparticles were found to be less toxic.^15,16,17

In the case of biosensors too, it is important that we consider important factors in the design and implementation of these sensors: (i) toxicity and biocompatibility; (ii) easy removability and washability for hygiene purposes; and (iii) robustness and high stability.^14,18,19 Since, the designing is specific for its usage as indicator of biomarker, the fabrication requires expansive skill.

SUMMARY AND CONCLUSION:

Every field involved in Health Care services must be dynamic and open to introducing newer methods and technology. The incorporation of Nanomedicine in Dentistry has opened new doors to increase the scope of dentistry and has made path-breaking changes in oral surgery, among other procedures. There is an increasing need for awareness about the futuristic and advanced forms of treatment provided today. Nanomedicine offers an opportunity for dentists to incorporate more biomimetic substances in dental treatment so that there is greater coordination between the nanostructures replacing the parts of the teeth with our body's regenerative processes.²⁰

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Received on 30.06.2020 Modified on 01.08.2020

Research J. Pharm. and Tech. 2021; 14(7):3976-3980.

DOI: 10.52711/0974-360X.2021.00689