Evaluation of Effect of Silver Nanoparticles Reinforced Double Antibiotic Paste on Inflammatory Biomarkers , Post Endodontic Pain and Periapical Healing in Teeth With Symptomatic Apical Periodontitis :a Parallel, Double-blind, Randomized Controlled Trial.

Background and rationale Apical periodontitis (AP) is an inflammatory condition that arises from bacterial infection in the necrotic root canal system causing local inflammation of periapical tissues. The infected pulp is the primary cause of apical periodontitis, resulting in destruction of periapical tissues and bone resorption. AP can be symptomatic or asymptomatic.

Symptomatic apical periodontitis (SAP) presents with spontaneous pain, tenderness to percussion/palpation, and pain on mastication. Radiographic signs may be absent early, but inflammatory mediators like pro-inflammatory cytokines IL-1β, TNF-α, IL-6, IL-8, matrix metalloproteinases (MMP-2, MMP-8, MMP-9), and mediators such as prostaglandin E2 (PGE2), substance P, and calcitonin gene-related peptide are markedly elevated. These molecules collectively contribute to periapical tissue destruction, bone resorption, and pain perception, reflecting the active disease state and host inflammatory response. Quantifying levels of proinflammatory and anti-inflammatory cytokines involved in these immune processes holds promise as potential biomarkers to objectively assess the presence or absence of endodontic disease. Biomarkers used to assess endodontic pathology can be collected from various oral and dental sites, including the dental pulp, dentin, saliva, and gingival crevicular fluid (GCF).

The collection of GCF involves a simple, fast, and noninvasive procedure that can be completed chairside, making it a promising tool to improve diagnosis in endodontics. Inflammatory markers collected in GCF have been widely studied in recent decades IL-1β and MMP 9 significantly increased in Apical Periodontitis Moreover, the persistence of intracanal microorganisms and their by-products, even after thorough chemo-mechanical debridement, remains the primary reason for endodontic failure. Enterococcus faecalis is one of the most resistant organisms associated with persistent periapical infections due to its ability to penetrate dentinal tubules and form biofilms. Therefore ICM are essential adjuncts for disinfection between appointments in multi-visit endodontic therapy to eliminate the bacteria.

Calcium hydroxide has been the gold standard; however, it demonstrates limited activity against E. faecalis and other resistant species. Long-term use of calcium hydroxide can reduce the fracture resistance of the teeth. Antibiotics are valuable alternatives for the management of bacterial infections. During endodontic treatment antibiotics may be applied systemically or locally. Due to the ineffectiveness of systemic antibiotics in necrotic teeth, the local application of antibiotics is a more effective mode for delivery during root canal treatment.Considering the polymicrobial nature of tooth infection, single empirical antibiotics are not able to provide a bacteria-free zone in the canal. It is essential to use a combination of antibiotics against all endodontic pathogens to prevent microbial resistance. The most practical combination in order to reach a sufficient result is Triple Antibiotic Paste (TAP).

TAP containing metronidazole, ciprofloxacin and minocycline has been proposed as a root canal medicament due to its antimicrobial effects. It is more useful in reducing bacterial count than calcium hydroxide .However among the components of the mixture, minocycline can induce tooth discoloration even in low concentrations.To avoid discoloration caused by minocycline, a double antibiotic paste (DAP) made of only metronidazole, and ciprofloxacin has been proposed which showed equal effectiveness as that of TAP. DAP not only provided better antimicrobial effect but also helps in reduction in pain almost equal in efficacy to TAP Moreover residual antibacterial efficacy of DAP is longer than that of TAP. Acc to Afsaneh Rahmati et al. DAP also shows significantly better outcomes compared to calcium hydroxide as ICM in the treatment of teeth with Periapical lesions. DAP offer a more effective therapeutic approach in managing necrotic pulps and apical periodontitis, potentially improving patient outcomes and treatment success rates. American Association of Endodontists recommended the use of diluted antibiotics (TAP) in a concentration of 0.1-1 mg/ml. However bacteria remain viable in dentinal tubules of teeth with apical periodontitis and this relatively low concentrations of DAP may not be effective against established bacterial biofilm.