Successful endodontic treatment primarily depends on effective disinfection of the root canal system through the integrated use of irrigants, intracanal medicaments, and sealers. While traditional agents such as sodium hypochlorite, ethylenediaminetetraacetic acid, calcium hydroxide, and zinc oxide eugenol have long been used, limitations in antimicrobial efficacy and biocompatibility have led the development of newer intracanal agents. Recent advancements, including nanoparticle-based, herbal, and bioceramic agents, offer superior biocompatibility, antimicrobial activity, and biofilm disruption. This review highlights the evolution, clinical relevance, and comparative properties of older and newer intracanal agents, emphasizing their roles in enhancing treatment outcomes through evidence-based approaches.
Key points
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Effective disinfection of the root canal system depends on the combined use of irrigants, medicaments, and sealers for successful endodontic treatment outcome.
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Advancements in endodontic materials, such as nanoparticle-based and bioceramic agents, offer improved antimicrobial efficacy with better biocompatibility.
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Although traditional agents such as calcium hydroxide and sodium hypochlorite are still considered the gold standard in endodontic procedures, there are still limitations for these agents.
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Evidence-based selection of intracanal agents is crucial for achieving optimal antimicrobial efficacy, while minimizing cytotoxicity and ensuring long-term clinical success.
Abbreviations
| AAE | American Association of Endodontists |
| AgNPs | silver nanoparticles |
| BCS | bioceramic-based sealers |
| Ca(OH) 2 | calcium hydroxide |
| Ca 2+ | calcium ions |
| CHX | chlorhexidine |
| CNPs | Chitosan NPs |
| DT | dentinal tubules |
| EDTA | ethylenediaminetetraacetic acid |
| EDTAC | EDTA with cetyltrimethylammonium bromide |
| ICM | intracanal medicament |
| MTA | mineral trioxide aggregate |
| MTAD | mixture of tetracycline, citric acid, and detergent |
| NaOCl | sodium hypochlorite |
| n-EDTA | nisin-incorporated EDTA |
| NP | nanoparticle |
| PDT | photodynamic therapy |
| PIPS | photoacoustic streaming |
| PLGA | poly lactic-co-glycolic acid |
| RCS | root canal system |
| REPs | regenerative endodontic procedures |
| SCAP | stem cells of apical papilla |
| SWEEPS | shock wave enhanced emission photoacoustic streaming |
| TAP | triple antibiotic paste |
| ZOE | zinc oxide eugenol |
Introduction
Optimal disinfection of the root canal system (RCS) is fundamental to the success of endodontic treatment. , According to the American Association of Endodontists (AAE), the term “intracanal medicament (ICM)” refers to a chemical agent that is placed within the RCS and retained between appointments, to alleviate pain and inhibit microbial activity. While ICMs are traditionally used to provide an extended antimicrobial effect between appointments, it is important to note that effectiveness of root canal disinfection is not exclusively reliant on these medicaments. To enhance the efficacy of endodontic treatment outcomes, concomitant use of irrigants, medicaments, and sealers is crucial in ensuring optimal disinfection.
Over the years, a wide range of irrigants, ICMs, and sealers have been developed to enhance treatment outcomes. Traditionally, sodium hypochlorite (NaOCl), ethylenediaminetetraacetic acid (EDTA), and calcium hydroxide (Ca(OH) 2 ) have been the gold standards for irrigation and intracanal disinfection, while zinc oxide eugenol (ZOE) and resin-based sealers have been commonly used for obturation. , However, advancements in material science, and an in-depth understanding of microbial resistance and biofilm behavior have led to the development of novel agents with enhanced antimicrobial properties, improved biocompatibility, and better sealing ability. , Newer nanoparticle (NP) or herbal agents, bioactive medicaments, and bioceramic-based sealers (BCS), offer promising alternatives by improving penetration, long-term stability, and interaction with dentin ( Fig. 1 ). The evolution of older and newer irrigants, medicaments, and sealers and their evidence-based applications in modern practice are explored in the following sections.
Schematic comparison of older versus newer intracanal agents based on antimicrobial activity, antibiofilm properties, and biocompatibility.
Endodontic Irrigants
Evolution
For endodontic therapy to be successful, effective removal of bacteria, necrotic pulp tissues, and accumulated inorganic debris is essential. Chemical preparation of the RCS is deemed required, since regardless of the instrumentation approach used, over 30% to 40% of the root canal surface remained uninstrumented. As a result, a number of irrigating agents, such as NaOCl, chlorhexidine (CHX), 17% EDTA, citric acid, and 37% phosphoric acid solution, amongst others, have been suggested for use in conjunction with canal preparation.
An ideal irrigant should completely remove the smear layer, lubricate the canal, efficiently kill microorganisms, induce no inflammation, and not damage the dentin. However, an irrigant that meets all these requirements is currently lacking. To date, there is no root canal irrigant that can dissolve both organic tissue and inorganic matter.
Strategies to overcome sodium hypochlorite limitations
Although newer irrigant solutions are introduced in dentistry, NaOCl still remains the gold standard. However, to improve its antibacterial efficacy and minimize toxicity, various strategies have been employed.
Irrigant activation systems
Irrigant activation systems in endodontics include photon induced photoacoustic streaming (PIPS), photodynamic therapy (PDT), and shock wave enhanced emission photoacoustic streaming (SWEEPS). PIPS and PDT enhances the penetration of NaOCl into the dentinal tubules (DT), increasing its bactericidal potency, while SWEEPS enables the use of NaOCl in lower concentration without minimizing its antimicrobial effect. These light-activated irrigation techniques also exhibit negligible apical extrusion, indicating their safer use for root canal disinfection. Additionally, the incidence of postoperative pain was minimal in laser activation compared to manual dynamic activation.
Newer and alternative irrigant solutions
NaOCl is highly cytotoxic and if the irrigant extrudes beyond the apex, severe tissue damage can occur. As a result, more biocompatible materials have been studied and discussed below.
Tetraclean NA
Citric acid-based irrigants were found to be the most efficient decalcifying agents. In vitro studies have shown better antimicrobial substantivity of TetracleanNA against Enterococcus faecalis in infected dentin, suggesting its potential use as a final rinse. In addition, its lower surface tension enables better DT penetration compared to a mixture of Tetracycline, Citric Acid, and Detergent (MTAD) and QMix.
Nanoparticles
Silver nanoparticles (AgNPs) are widely experimented as a viable alternative to NaOCl, owing to its ability to penetrate deeper into the DT and eliminate endodontic biofilms. However, its potential cytotoxicity and tooth discoloration must be further studied. , Compared to other biomaterials, chitosan oligosaccharide exhibits higher antimicrobial, antioxidant, and antiinflammatory properties. Laser activation of irrigant with 0.2% chitosan has shown higher smear layer removal at the apical third of the RCS. On the other hand, PDT and chitosan demonstrated an enhanced antibacterial potential against E faecalis . , Chitosan NPs (CNPs) have also been found to reduce the harmful effects of NaOCl. Besides these agents, various other NPs are being explored for their antimicrobial properties. However, their clinical application is limited.
Herbal agents
In the recent years, various herbal irrigants have been investigated. Numerous varieties of eucalyptus extracts have been proven to have antimicrobial effects on E faecalis , Streptococcus mutans , C. albicans, and Lactobacillus . Other most commonly examined agents for their antimicrobial efficacy include propolis, triphala, aloe vera, and 0.6% carvacrol, amongst others. Although, these agents exhibited bactericidal activity, they were not as potent as NaOCl. However, they were least detrimental to root dentin microhardness compared to conventional irrigants.
Ozonated water
A recent systematic review concluded that ozonated water, though comparable at the level of disinfection, is not a better disinfecting irrigant than NaOCl and CHX. It can be used as a final irrigant instead of EDTA, since it removes the smear layer, improving the bond strength between sealer and dentin with minimum impact on marten hardness.
Strategies to overcome limitations of ethylenediaminetetraacetic acid
17% EDTA is considered the conventional chelating agent in endodontics due to its enhanced potential to remove smear layer, release of growth factors in regenerative endodontic procedures (REPs), and its compatibility with NaOCl. However, it also exhibits cytotoxicity and inflammatory effects. As a result, modifications have been made to overcome these disadvantages ( Table 1 ).
Table 1
Endodontic irrigants: mechanisms, key effects and limitations ,,,,
| Endodontic Irrigants | Mechanism of Action/Properties | Key Effects/Uses | Limitations |
|---|---|---|---|
| NaOCl | Decomposes into HOCl (antimicrobial and proteolytic), and chlorine gas (antimicrobial) | Dissolution of organic and inorganic tissues, antimicrobial |
Cytotoxic and can damage periapical tissues when accidentally extruded
Decomposes at room temperature |
| CHX | Positively charged and it binds to the negatively changed bacterial cell wall |
Bacteriostatic effect in low concentrations
Bactericidal at high concentration |
No proteolytic activity, therefore, does not penetrate into the biofilm matrix
Cannot be used as a stand-alone irrigant |
| EDTA | Complex molecule that binds to metal ions, forming a chelator | Removes smear layer, allowing NaOCl to penetrate further into the tubules |
Insignificant antimicrobial activity. After all ions are bound, it is no longer reactive
Though time dependent, the microhardness of dentin can be reduced |
| EDTA, CHX and detergent (QMix) | Contains EDTA, chlorhexidine gluconate, and a detergent | Antimicrobial with effective chelation properties- more open dentinal tubules after smear layer removal | If using NaOCl with Qmix, then an intermediate solution such as saline must be used to avoid precipitate formation |
| MTAD | Mixture of tetracycline, citric acid, and detergent- a surfactant mixture used as final irrigant |
Minimal impact on dentin microhardness compared to Qmix
As effective as EDTA in removing smear layer |
Push out bond strength similar to NaOCl, but chelator qualities need further study.
Not as effective at smear layer removal compared to Qmix and EDTA |
| EDTAC | EDTA with surfactant | Irrigating 17% EDTAC for 1 min optimally removes smear layer without erosion | After 1 min, there is no significant difference in dentin microhardness between EDTA and EDTAC |
| N-EDTA | Nisin incorporated Ethylenediamine tetra Acetic Acid was prepared with high-performance liquid chromatography |
Had negligible cytotoxicity compared to MTAD
Similar smear layer removal ability compared to MTAD |
Can be a potential alternative irrigant. However, further studies are necessary to understand its limitations |
| Tetraclean NA | Tetraclean NA is citric acid, cetrimide, and polypropylene glycol |
Antimicrobial activity against
E faecalis
.
Enhanced penetration into dentinal tubules due to lower surface tension |
Further studies needed to show any improvements in bond strength |
| AgNPs | Disrupt bacterial cell membranes and biofilm formation |
Effectively eliminate endodontic biofilms
Penetrate deeper into dentinal tubules Gradually increase dentin hardness |
Potential cytotoxicity and tooth discoloration must be further studied |
| Chitson Oligosaccharide | Exhibits higher degree of deacetylation and polymerization; lower molecular weight and viscosity; completely water soluble |
Antimicrobial, antibiofilm, antioxidant, and antiinflammatory properties
Effective drug carrier |
Not the most effective in removing calcium hydroxide |
| PHMB |
Cationic antiseptic with a wide spectrum of antimicrobial, antifungal, and antiviral activity
Disrupts the osmoregulation and metabolic activity of the bacterial membranes and enzymes, leading to cell death |
Antimicrobial activity against
E faecalis
and S. epidermidis from the mature dentin biofilm
Antibacterial activity against pathogens causing apical periodontitis |
Minimal tissue dissolving and smear layer removal properties
Limited research and clinical evidence |
| O3 Water | O3 dissociates into reactive oxygen species, damaging bacterial cells | Biocompatible, good final irrigant since it improves the bond strength with minimum impact on Martens hardness | Minimal disinfecting properties compared to NaOCl and CHX |
| Herbal Irrigants | Citric acid releases Transforming growth factor-beta 1 in regenerative endodontic cases |
Eucalyptus extracts- antimicrobial effects on
E faecalis
, S. mutans, C. albicans and Lactobacillus
Least detrimental to root dentin microhardness |
Further studies are needed to assess the antimicrobial and smear layer removal effects compared to traditional irrigants |
| HOCl |
NaOCl decomposes to HOCl (antimicrobial and proteolytic action) and chlorine gas (antimicrobial).
Chlorine derived from NaOCl can take 2 forms: OCl- or HOCl |
Both are antimicrobial and has proteolytic effect, dissolving lipids and neutralizing amino acids. |
Effects are heavily based on available chlorine gas
Further studies are necessary to determine potential limitations |
Abbreviations: HOCl, hypochlorous acid; O3, ozone; OCl-, hypochlorite; PHMB, polyhexamethilene biguanide.
Mixture of tetracycline, citric acid, and detergent MTAD removes smear layer with significantly less erosion of the dentin surface when compared to EDTA. The presence of citric acid aids in its chelating property, enabling the penetration of doxycycline into the DTs for a sustained antibacterial effect. It also exhibits solubilizing action on dentin and pulp comparable to that of conventional EDTA and citric acid (5%).
Ethylenediaminetetraacetic Acid with Cetyltrimethylammonium bromideEDTA with cetyltrimethylammonium bromide (EDTAC) facilitates optimum smear layer dissolution. Nonetheless, its ability to erode the dentin surface is time dependent; shorter duration of exposure leads to negligible erosion, whereas prolonged irrigation can cause degradation of collagen and reduces the hardness of the dentin. EDTAC enhances the wettability of dentin for the flow and adhesion of the sealer when used as a final irrigant. Lasing EDTAC considerably improved smear layer removal compared to hydrogen peroxide, and also offers photothermal disinfection benefits.
Nisin-incorporated ethylenediaminetetraacetic acidNisin incorporated into EDTA has similar cytocompatibility when compared to MTAD. Besides aiding in the removal of smear layer, it also exhibits enhanced antibacterial and antibiofilm properties. Therefore, with further studies, nisin-incorporated EDTA (N-EDTA) could be considered as an alternative irrigant.
QMix
QMix demonstrated better debridement of smear layer from the apical 1/3rd of RCS compared to NaOCl, EDTA and CHX. It is biocompatible and exhibits higher bond strength with endodontic sealers/bonding agents and dentin. Irrigation with NaOCl and Qmix resulted in greater sterilization of canals. Nevertheless, surfactants in Qmix besides increasing its penetration into dentin, also resulted in the reduction of dentin microhardness.
SmearClear
A mixture of 17% EDTA, cetrimonium bromide and surfactant, called SmearClear, has been investigated for its chelating and disinfecting properties. The ability to remove calcium ions (Ca 2+) from the root canal was most efficient with SmearClear followed by MTAD.
To conclude, AAE guidelines 2016, states that the use of 1.5% NaOCl and 17% EDTA as irrigants is still considered the standard due to their effective removal of organic and inorganic substances. However, in certain cases with higher risk of NaOCl extrusion such as open apex, apical bony fenestration, and iatrogenic factors, alternative irrigants can be considered. ,
Intracanal Medicaments
Evolution
During the late 19th and early 20th centuries, ICMs were introduced with the goal of achieving a sterile root canal environment, as confirmed by bacterial sampling before obturation, to prevent endodontic failure. Various volatile agents and combination of medicaments were experimented to achieve this unattainable state. Phenolic compounds and aldehydes were most commonly used for their germicidal action. Application of these agents has drastically reduced due to their carcinogenic effects. Various traditional ICMs, their mechanism of action, and the potential disadvantages that led to the cessation of use are mentioned in Table 2 .
Table 2
Traditional intracanal medicaments: agents not commonly used and/or banned due to toxicity, inefficiency, or safety concerns ,,,
| Medicament | Mechanism of Action | Key Effects/Uses | Limitations |
|---|---|---|---|
| Eugenol |
Suppression of voltage gated sodium channels, and inhibits impulse transmission
Inhibiting the synthesis of prostaglandins Disrupts bacterial cell membrane |
Antioxidant, analgesic, antimicrobial, and antiinflammatory | Local tissue irritation, allergic reactions in patients and dental professionals (contact dermatitis) |
|
PCP
CPCP CMCP |
Denaturation of proteins, enzyme deactivation, and damage to the cytoplasmic membranes of bacteria
Release chlorine that inactivates sulphydryl-group-containing enzymes |
Bactericidal activity
Camphor- diluting agent and vehicle; mitigates the irritating effects of unadulterated phenol or parachlorophenol |
Cytotoxic and/or antigenic effects |
| Thymol | Causes tension and instability of bacterial cell membranes | Antibacterial | May have allergenic properties |
| Formocresol | Antimicrobial vapors are released by the volatile chemical formaldehyde which acts as a germicide | Germicidal | Potential carcinogen, mutagenic, and genotoxic |
| Glutaraldehyde | Protein cross-linking affects the bacterial cell wall, suppression of transport mechanisms within cells | Disinfection | Occupational asthma, breathing difficulties, respiratory irritation, eye itching, rhinitis and skin rashes |
| Iodine-potassium iodine | Iodine interacts with the disulphide bonds in the bacterial enzymes and causes disruption | Antimicrobial activity | Dentin discoloration from prolonged exposures. May also cause allergenic reactions |
| Chloramine T | The extended antibacterial action of chloramine-T is caused by the relatively slow release of reactive chlorine | Antimicrobial shows reduced cytotoxicity as opposed to NaOCl | Higher concentrations will result in increased cytotoxicity |
| Aminoacridine | Blocks bacterial protein synthesis | Low strength antiseptic | Frequently used as an irrigant due to low surface tension |
| PBSC | Gram-positive bacteria were treated with penicillin, penicillin-resistant bacteria with bacitracin, gram-negative bacteria with streptomycin, and yeasts with sodium caprylate | Poly-antibiotic | Banned use of PBSC for intracanal treatments because of possible penicillin allergy and sensitization potential |
| PBSN | Sodium caprylate replaced with nystatin/neomycin | Poly-antibiotic and antifungal | Penicillin allergy |
Abbreviations: CMCP, camphorated monochlorophenol; CPCP, camphorated parachlorophenol; PBSC, penicillin, bacitracin, streptomycin, and caprylate sodium; PBSN, Penicillin, Bacitracin, Streptomycin, and Nystatin; PCP, parachlorophenol.
The shift toward biocompatible and targeted antimicrobial agents led to the widespread adoption of Ca(OH) 2 (introduced in the 1920s by Hermann) as a standard ICM. Its high alkalinity, bactericidal properties, and ability to induce hard tissue formation made it a revolutionary addition to endodontic therapy. Later, antibiotic-based pastes such as triple antibiotic paste (TAP) was developed to address persistent infections. However, concerns regarding antibiotic resistance have driven interest in herbal and nanoparticle-based medicaments, which offer antimicrobial action with fewer side effects.
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