ABSTRACT

Abstract (706 words)

A 2016 Global Burden of Diseases study highlighted that around 3 billion people worldwide are affected by dental caries. To alleviate this burden of oral healthcare, especially for high caries-risk patients, dental caries prevention is inevitable. However, enhanced measures are needed to counter the caries process in high-risk patients given the affected population with the existing preventive regimens. In recent years, arginine (Arg)-fluoride (F) interventions for caries prevention have gained research interest due to their biofilm modulation potential targeted for high caries-risk patients. The caries preventive potential of Arg in Duraphat® (professionally deliverable 5% NaF varnish) was investigated through several in vitro studies to demonstrate a superior anti-caries effect than Duraphat®. While the caries preventive potential of Arg in other F-containing varnishes is unknown. Moreover, Duraphat® contains an excipient olophony which might trigger a hypersensitivity reaction in asthmatic/allergic patients and is thus contraindicated. With biotic-F strategies being imperative given the global burden of dental caries, it is essential to identify whether Arg incorporation in other professionally deliverable F-containing agents demonstrates a promising caries preventive potential.

Therefore, as a primary exploratory study examining the F release potential of Arg-incorporated F varnishes, the original research presented in this thesis was undertaken.

The planned original research was based on the results of a systematically conducted scoping review with the objectives to investigate the caries preventive potential of professionally deliverable F-containing agents with incorporated Arg and identify the future scope of research on Arg-F interventions for caries prevention. PubMed, SCOPUS, and Web of Science databases were systematically searched to include in vitro studies, clinical trials, systematic reviews with/without meta-analysis, umbrella reviews, systematic scoping reviews, and narrative reviews examining the effect of professionally deliverable Arg-F interventions on caries prevention. Data were extracted as per the pre-determined variables in the registered protocol. Further, the evidence was synthesized and discussed based on study designs. Of 124 records identified, 7 articles (6 in vitro investigations and 1 scoping review) were included for a complete review with no clinical studies with/without appraisal.

Arginine variants — L-Arg and L-Arg.-HCl were examined for a potential professional application aimed at caries prevention being reported with in vitro studies and concentrations ranging from 1% - 10 % w/v. Four in vitro studies explored L-Arg enriched 5% NaF varnish (Duraphat®) as a promising caries preventive agent. While only 1 study each, considered incorporating L-Arg in MI varnish®/nanohydroxyapatite and glass ionomer cement for primary/secondary and tertiary caries prevention, respectively. While the scoping review highlighted the scope for incorporating Arg to professionally deliverable F-containing agents. It was concluded that Arg-F varnish was predominantly investigated through in vitro studies and the data so far suggest that Arg was exclusively incorporated in Duraphat®. The caries preventive potential of Arg in other F-containing varnishes remains unexplored.

Based on the identified research gap, the original study was performed with 4 commercially available F varnishes with distinct F content, namely — Duraphat® (5% NaF), Fluor Protector® (0.9% SiH2F2), Fluor Protector S® (1.5% NH4F), and Fluorimax™ (2.5% NaF). L-arginine (2% w/v.) was incorporated in these varnishes to estimate the F release potential at 1 h, 4 h, 6 h, 24 h, 3 days, and 7 days using F-ion selective electrode attached to a potentiometer. In addition, at predetermined time-points media pH of eluded varnishes was estimated with a PH electrode and the primary inorganic F extraction was performed to identify any potential chemical interplay with Arg in F varnishes. For all experiments, a negative control group (no varnish) was included to eliminate characterized media contaminants. The en masse measured pH for the experimental groups was significantly higher than the controls (p<0.01) with inconsistencies recognized at a time point for Fluor Protector S® (Arg-containing varnish <control) and Fluorimax™ (p=0.166). For all time points, the F release for the Arg-containing groups was significantly higher than the control groups (p<0.001). Similarly, the computed integrated mean and cumulative F releasefor the experimental (with Arg) groups was significantly higher than the commercial controls (p<0.001). The primary extracted F concentrations for the Arg-containing groups were significantly lower than the control groups (p<0.001) demonstrating a chemical interplay with Arg incorporation. Under the conditions of the study, it was concluded that irrespective of the inorganic F content, incorporating Arg in F-containing varnishes increases their F release potential.

Keywords: Arginine, caries prevention, fluoride, professionally deliverable agents, varnish.