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 Table of Contents  
REVIEW ARTICLE
Year : 2019  |  Volume : 11  |  Issue : 3  |  Page : 167-173

Nanoparticles: A promising novel adjunct for dentistry


1 Department of Conservative Dentistry and Endodontics, Dr. Harvansh Singh Judge Institute of Dental Sciences and Hospital, Panjab University, Chandigarh, India
2 Department of Private Practitioner, Dr. Harvansh Singh Judge Institute of Dental Sciences and Hospital, Panjab University, Chandigarh, India

Date of Web Publication3-Jul-2019

Correspondence Address:
Jagat Bhushan
Dr. Harvansh Singh Judge Institute of Dental Sciences and Hospital, Sector 25, Panjab University, Chandigarh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJDS.IJDS_26_19

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  Abstract 


Nanotechnology has delivered is impact on almost every facet of science and development. It is but natural that medicine and dentistry too are being influenced by this recent entrant which has immense potential. In contrast to bulk material, these nanoparticles are much more potent and can be manipulated for surface chemistry, charge and bonding capability. This article is a brief overview of current knowledge of nanoparticles and their actions, especially in reference to dentistry.

Keywords: Antibacterial, dentistry, nanoparticles


How to cite this article:
Bhushan J, Maini C. Nanoparticles: A promising novel adjunct for dentistry. Indian J Dent Sci 2019;11:167-73

How to cite this URL:
Bhushan J, Maini C. Nanoparticles: A promising novel adjunct for dentistry. Indian J Dent Sci [serial online] 2019 [cited 2019 Sep 17];11:167-73. Available from: http://www.ijds.in/text.asp?2019/11/3/167/261946




  Introduction Top


Antibiotics both topical and systemic have served the purpose of elimination of microorganisms since time immemorial. However, the evidence of complete elimination of pathogens, especially methicillin-resistant Staphylococcus aureus and vancomycin-resistant streptococci, has not been substantiated adequately. These antibiotic-resistant microorganisms employ an array of different characteristics to defy the antimicrobial action of exchange of genetic materials, thickening of the peptidoglycan wall, or deficiency of the porin channels. The increasing resistance against such bacterial species is on the rise and poses a major threat to various treatment modalities, causing higher treatment failures. To combat this, the concept of endodontic nanoparticles (NPs) has been introduced. These NPs have undergone very immense investigation due to their potential for application in many fields, ranging from biomedical, drug delivery, defense and security, medicine to electronics. The aim of this article is to have a brief overview into the present status, ongoing progress, and potential implications of NPs in dentistry more so in reference to endodontics.


  Definition Top


The advent of nanotechnology has become a powerful tool for various dental procedures such as biointegration, dental restorations, and dental tissue engineering.

The European Commission's Recommendation states that “nanomaterial” means a natural, incidental, or manufactured material containing particles, in an unbound state or as an aggregate or as an agglomerate and where, for 50% or more of the particles in the number size distribution, one or more external dimensions is in the range 1–100 nm.[1]


  Classification of Nanoparticles Top


The NPs can be classified under three main categories as follows:

  1. On the basis of origin, NPs can be classified as:


    1. Natural
    2. Artificial.


  2. On the basis of dimension, they are classified as zero-dimensional or nanostructures such as NPs, one-dimensional or nanorods, and two-dimensional or thin films refer to [Figure 1][2],[3]
  3. On the basis of structural configuration, they are described as carbon-based NPs, metal NP, dendrimers, and composites.[2],[3]
Figure 1: Classification of nanoparticles

Click here to view



  What Makes Nanoparticles Different from the Bulk Materials? Top


When compared with bulk materials, the NPs provide greater benefits as they are relatively low stability molecules having low coordination and unsatisfied bonds that allow them to interact with other particles effectively and with ease. Added to this, they exhibit quantum confinement effects in materials with delocalized electrons.[4],[5] Moreover, the high surface area to volume ratio plays a major role in determining the energy statistics of the particles. The concept of NPs as antimicrobial agents is very novel and utilizes quite different mechanisms which are in contrast to antimicrobial mechanisms of the antibiotics. Therefore, antibiotic resistance becomes a redundant issue. Not only do they disrupt the process of cell wall synthesis as done by the conventional bulk materials, but NPs also have the potential of inhibiting various enzymes, such as DNA-dependent RNA polymerase and DNA gyrase. Furthermore, chemical, magnetic, electrical, mechanical, and optical alterations and modifications can be undertaken to attain more benefits.


  Properties of Nanoparticles Top


The antimicrobial NPs have managed to grab attention for the treatment of infections pertaining to the oral cavity environment. This is possible because of their various physiochemical properties that include their different behavior with different substances, their antiadhesive nature, their biocidal characteristics, and their potentially satisfying delivery capability. Various surface characteristics of the NPs are due to their surface interaction with plasma proteins that restricts their uptake by the reticuloendothelial system.[6] Physical and chemical properties of the NPs can be explained under four headings.

Size

Size of the NP plays a pivotal role. They need to have an optimum size typically in the range of 10–100 nm. Sizes <10 nm and >100 nm are not able to exhibit the therapeutic effect because very small particles are steered clear of the body through kidneys and very large particles are taken up by the reticuloendothelial system for disposal.[7]

Surface charge

Surface charge has influence on the antimicrobial efficacy because suitably charged NPs can easily get attached to oppositely charged cell walls of the microorganisms, thus potentiating their effect. A strong charge will allow higher efficacy but on the other hand would compromise the stability of the NP formulation resulting from electrostatic repulsive forces among the NPs. Hence, NPs need to be optimally charged in relation to both negative/positive charging and amount of charge.[8]

Surface composition

The hydrophilic and biocompatible coating and high surface area/volume ratio both improve the interaction of NPs with the cellular receptors which can be further improved by binding ligands on the surface of NPs, thereby suiting various bioapplications. Surface composition becomes a very important parameter because of very high surface area-volume ratio possessed by the NPs. To quote an example, this surface composition has been very optimally exploited through the use of superparamagnetic iron oxide NPs for various biomedical applications owing to their low toxicity as well as biodegradability because iron product is recycled by the cells.

Protein adsorption

Certain polymers such as polyethylene glycol when coated on the NP surfaces inhibit protein adsorption which increases their half-life because circulating plasma proteins have a high affinity for the surface of the NP and quite a high number of these proteins have the potential to act as opsonins, making it prone to recognition and subsequent phagocytosis by monocytes and macrophages, thereby causing rapid removal from the body.[9],[10],[11],[12]


  Functionalization Top


Raw NPs normally are found lacking the desired properties for biomedical applications and have issues with their stability/target application/delivery at the target site. Hence, these are combined with certain other molecules to suitably modify the surface composition/structure/charge. As a result of functionalization, the NP may be the core which may have adsorption/coating of certain other materials. This surface may further have a molecule attached to it so that it becomes biocompatible and makes the assembly efficient to bind to the target site. This functionalization often utilizes covalent bonding/noncovalent bonding and/or encapsulation.


  Synthesis Top


There are two different types of approaches by which we can prepare NPs.

  1. Top-down approach
  2. Bottom-up approach.


The top-down approach reduces the size of the material from bulk to nanoscale utilizing special treatments such as grinding/ablation/etching/sputtering. The bottom-up approach is preparation of NP/nanostructures utilizing mostly chemical reactions.

Various methods that have been employed include:

  1. Chemical (by monomer formation, accumulation, nucleation, and growth)[13]
  2. Electrochemical (two-electrode system where bulk metal will be kept in an anode and transformed into metal crystals)[14],[15]
  3. Wet chemical (using ultrapure water and stirring motion)
  4. Pyrolytic (atomizing the solution and mixing with soluble polymers)
  5. Microwave (using deionized vacuum, absolute ethanol, and irradiation with microwave energy)
  6. Hydrothermal (using solvents and mineralizers in autoclaves and reactors)[16],[17]
  7. Mycosynthesis (using fungal filtrate, precipitation, and calcination)[18]
  8. Sonochemical (involving high-intensity ultrasound sonication of metal salt and oxygen)[15]
  9. Solution-gel (involves condensation and hydroxylation of precursor molecules)
  10. Co-precipitation (salt precursor is converted to metal hydroxide in an aqueous medium with the addition of ammonium hydroxide or sodium hydroxide)[19],[20]
  11. Biosynthesis (using plant extracts or microbial secretions to facilitate the formation of MeO-NP).[21]



  Application Top


The ongoing research to attain benefits of NP has increased manifold and finds application in various dental and medical fields. They are used as drug delivery vehicles to achieve biomedical benefits. They find their use in agriculture, food, cosmetics, paints, biotechnology, textiles, optical as well as engineering communication, electronics, metallurgy, defense, security as well as energy storage. Nanotechnology is a boon for the dental world. It can be applied in various branches of dentistry for various procedures.

  1. Conservative dentistry aids in restorations, to cure dentin hypersensitivity,[22] and can be used to enhance the effects and properties of bonding agent such as nanosolutions (nanoadhesives)[23] and polymers
  2. Endodontics is as an effective endodontic irrigant after cleaning and shaping of the canals to get rid of the oral microflora
  3. Prosthodontics for implants (growth factors and antibiotics incorporated as CaP coating on Ti implants),[24] impression materials (incorporated nanofillers in traditional vinyl poly siloxanes),[23] nanocomposite denture teeth,[25] etc.
  4. Oral diagnosis for the diagnosis of oral cancer (using photosensors and carriers,[26] nanoscale cantilevers, nanopores, nanotubes, and quantum dots) and treatment of oral cancer (using nanovectors for gene therapy and nanomaterials for brachytherapy)[27]
  5. Oral surgery for bone replacement method, as nanoanesthesia by nanorobots.[22] It can also be used in surgery as nanoneedles, nanotweezers,[28],[29] and nanosterilizing solution [30]
  6. Periodontics as dentifrobots (dentifrices made up of nanosized hydroxyl apatite molecules),[22] drug delivery methods, tooth repositioning,[29] nanosized titanium on skin that allows disintegration of particles for periodontal therapy [25]
  7. Orthodontics as nanoflex orthodontic wires with excellent deformability, corrosion resistance and strength,[31] tooth repositioning by orthodontic nanorobots [22]
  8. Dental materials as nanocomposites that change the superficial enamel layer by sapphires and diamond,[31] nanolight-curing glass ionomer restorative [29]
  9. Drug delivery in nanotherapeutics (leading to the reduction in dosage and adverse effects of drugs and can be used for Alzheimer's disease and Parkinson's disease).[32],[33],[34] Nanoencapsulation wherein new vaccines and antibiotics have been developed that have made possible the targeted delivery of genes and drugs to the human liver.[29],[35]



  Mechanism of Antimicrobial Action Top


The mechanism for antimicrobial activity is yet not fully understood and is being extensively investigated. This action may be caused by one or more mechanisms, but the most prominent mechanism in majority of the NPs is the generation of reactive oxygen species (ROS) and damage to the cell membrane refer to [Figure 2].
Figure 2: Mechanism of action of nanoparticles

Click here to view


Some of the possible mechanisms are given below.

Cell membrane disruption by electrostatic interaction

Generally, the microorganisms and their spores carry a negative charge on their surface, so an NP with opposite charge has high affinity for the surface of microorganisms and accumulates on the microbial cell surface. These positively charged NPs bond strongly with the cell membrane causing disorganization of the cell wall which is a causative factor for increasing the permeability allowing entry of more and more NPs into the microbe and further damage it by causing leakage of cellular contents. These NPs not only bind with the cellular membrane but also have a great potential to bind to mesosomes, thereby affecting respiration, division, as well as DNA replication.[36],[37]

Metal ion homeostasis

Regulation of metabolic functions is primarily dependent on metal ion homeostasis in the microbes. Excess of metal-based NPs disturbs this essential parameter for the survival of the cell causing irreversible damage and enforcing either retardation of growth or killing of the microbe.

Reactive oxygen species production

NPs after gaining access through the cell membrane of the microorganism cause release of ROS which cause oxidative stress within the cell and initiate multiprompt attack on the microbe. It inhibits the respiratory activity, decreases ATP production, and causes distortion and disruption of the cellular membrane. As soon as metal oxide NP is inserted into the bacterial cell, the formation of ROS occurs by active redox cycling, by cell–particle interaction, and by the pro-oxidant functional group on metal oxide NP surface.[38]

Protein and enzyme dysfunction

NPs catalyze the oxidation of amino acid side chain, leading to the formation of protein-bound carbonyls that cause loss of catalytic activity, leading to protein degradation and inactivation of various essential enzymes.[39],[40]

Genotoxicity and signal transduction inhibition

NPs have an ability to interact with the nucleic acid because of their electrical properties and have a negative influence on the replication process of chromosomal as well as plasmid DNA which is resultant to inhibition of signal transduction.[41],[42],[43],[44]

Other mechanisms

Photokilling

In the presence of light, photosensitized NPs cause photochemical alteration of the cell membrane as well as damage to the proteins, especially DNA causing photokilling of the microorganism.[45] Photothermal killing is also being explored for biomedical applications.

A complete understanding of the exact mechanisms is still not there, but a huge number of studies are being done worldwide and hopefully, yet elusive understanding is expected to be available soon.


  Strategies for Using Antibacterial Nanoparticles Top


The antibacterial NP can be used all by itself or as an adjunct or a combination of the above. According to the literature, nano-based formulations provide better penetration and allow slow and controlled release of active ingredients at target site.[46],[47],[48],[49]

The various strategies include:

  • Using NP itself as a novel antibacterial agent
  • Using functionalized NP to provide therapeutic effects
  • Supplementation of antimicrobial photodynamic theory
  • Incorporation into other media such as root canal sealer such as EndoSequence BC Sealer and gutta flow.



  Availability Refer to Figure 3 Top


Organic nanoparticles

Chitosan nanoparticles

Chitosan (poly,(1,4)β-d glucopyranosamine), a derivative of chitin, the second most abundant natural biopolymer, has received significant interest in biomedicine. The industrial extraction of chitin is generally obtained from crustaceans such as crabs, lobsters, and shrimps. The structure of chitin resembles that of cellulose, and both act as a structural support and defense material in living organisms. Chitosan and its derivatives such as carboxymethylated chitosan showed a broad range of antimicrobial activity, biocompatibility, and biodegradability. Due to its chelating property, sequesters trace metals/essential nutrients and inhibit enzyme activities essential for bacterial cell survival.
Figure 3: Availability of nanoparticles

Click here to view


Poly (lactic) coglycolic acid

Synergism effect of light and methylene blue-loaded NP in the reduction of bacterial counts in both planktonic phase and root canal has been found. It has been concluded that the use of poly (lactic) coglycolic acid NPs encapsulated with photoactive drugs might be a promising adjunct in antimicrobial endodontic treatment.[50]

Nonorganic nanoparticles

  • Bioactive glass
  • Bioactive mesoporous calcium silicate NPs
  • Tetracycline loaded-calcium-deficient hydroxyapatite nanocarriers.


Bioactive glass nanoparticles

Bioactive glass consists of SiO2, Na2O, and P2O5 at different concentrations. They are amorphous, ranging from 20 to 60 nm in size.

  1. High pH: Increase in pH due to release of ions in an aqueous environment
  2. Osmotic effects: Increase in osmotic pressure above 1% is inhibitory for many bacteria
  3. Ca/P precipitation: Induced mineralization of the bacterial surface.


Mesoporous calcium silicate

These are NPs (around 100 nm) with high specific surface area and pore volume for potential application of filling an apical root canal of a tooth.[51]

  • Injectability
  • Apatite mineralization
  • Osteostimulation
  • Drug delivery
  • Antibacterial efficiencies.


Tetracycline-loaded calcium-deficient hydroxyapatite

Osteoconductive drug delivery system composed of apatitic nanocarriers capable of providing sustained delivery of tetracycline in the periodontium.[52]

Metal nanoparticles

  • ZnO
  • Gold
  • Silver
  • TiO2
  • Si
  • MgO and CaO.


Zno nanoparticles

  • Mechanism


    • ROS generation on the surface of the articles
    • Zinc ion release
    • Membrane dysfunction
    • NPs internalization into cell.


  • Photocatalytic activity
  • High stability
  • Bactericidal effects on both Gram-positive and Gram-negative bacteria
  • Antibacterial activity against spores which are resistant to high temperature and high pressure.[53],[54],[55],[56],[57],[58]


Au nanoparticles

  • Mechanism


    • Attachment of these NPs to membrane which changes the membrane potential and then causes a decrease in ATP level
    • Inhibition of tRNA binding to the ribosome.


  • Nontoxicity, not inducing any ROS-related process
  • High ability to functionalization
  • Polyvalent effects
  • Ease of detection
  • Photothermal activity.[59],[60],[61],[62]


Silver nanoparticles

  • Use of silver compounds and NPs is widespread mainly owing to its antibacterial property
  • The antibacterial property of silver is mainly due to its interaction with sulfhydryl groups of protein and DNA, altering the hydrogen bonding, respiratory chain, unwinding of DNA, and interference with cell wall synthesis/cell division [63]
  • Silver in its metallic states inert but in the presence of moisture is ionized and forms silver ions. These silver ions are highly reactive, bind to tissue proteins, and induce tissue changes. These silver ions bring about structural changes in the bacterial cell wall and nuclear membrane barrier and result in cell death
  • Two main issues of using silver NPs are the potential browning/blackening of dentin and toxicity toward mammalian cells
  • The Ag NPs of different shapes (triangular, spherical, and rod) were tested against Escherichia coli[64]
  • A triangular nanoplate has a high percentage of{111} facets whereas spherical- and rod-shaped Ag NPs predominantly have {100} facets along with a small percentage of {111} facets
  • The {111} facets have high atom density, which is favorable for the reactivity of Ag.


TiO2 nanoparticles

  • Mechanism


    • Oxidative stress via the generation of ROS
    • Lipid peroxidation that causes to enhance membrane fluidity and disrupt cell integrity.


  • Suitable photocatalytic properties
  • High stability
  • Effective antifungal for fluconazole-resistant strains.[57],[65],[66],[67],[68]


Si nanoparticles

  • Influencing the cell functions such as differentiation, adhesion, and spreading
  • Nontoxicity
  • Stability.[67],[69],[70]


CuO nanoparticles

  • Mechanism


    • Crossing of NPs from the bacterial cell membrane and then damaging the vital enzymes of bacteria.


  • Effective against Gram-positive and Gram-negative bacteria
  • High stability
  • Antifungal activity.[56],[71],[72]


MgO and CaO nanoparticles

  • Mechanism


    • Damaging the cell membrane and then causing the leakage of intracellular contents and death of bacterial cells.


  • Effective against both Gram-positive and Gram-negative bacteria
  • High stability
  • Low cost
  • Availability.[70],[73],[74],[75],[76]



  Conclusion Top


Antibacterial NP-based treatment has the potential to improve antibacterial/antibiofilm efficacy. They have distinct advantages when applied in dentistry/endodontics. The whole concept of nanotechnology in healthcare should be accepted with positive zeal and caution for future development.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Introduction
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