Nanocurcumin mediated photodynamic therapy as a novel approach for root canal disinfection: ex-vivo study

Antibacterial photodynamic therapy has gained popularity in the field of endodontics to enhance root canal disinfection strategies [1]. This is particularly important in case of resistant infections and post-treatment disease [2]. One of the main microorganisms recovered from root filled teeth with post-treatment apical periodontitis is Enterococcus faecalis [3]. Indeed, E. faecalis is one of the main pathogens implicated in endodontic treatment failures [4]. Several studies have previously shown that E. faecalis is capable of surviving and even forming biofilm in the presence of medicaments like calcium hydroxide [5,6] or antibiotics [7,8]. Consequently, the incorporation of adjunctive approaches like antibacterial photodynamic therapy (aPDT) has been recommended to achieve successful treatment outcomes [9]. Recent systematic reviews have shown that aPDT has still not shown conclusive results as compared to other intracanal disinfection techniques [9,10].

The mechanism of aPDT is based on three key factors: photosensitizer (PS) (a non-toxic dye), target cell or tissue, and a light source with a specific wave length [11,12]. PSs have a stable electronic configuration set at the lowest or ground state level. By activation of the PS with light source, the PS is promoted from the ground state to an excited state (singlet state), meaning, electrons move to higher energy orbitals. This singlet state is unstable with an ultimately short lifetime thus these electrons are liable to lose their excess energy and return to ground state by emitting light or heat. Moreover, changes in electron spins can also alter the molecule to the triplet state. This process is known as “intersystem crossing”. The triplet state PS reacts with the substrate or cells in two different pathways; namely a type I and type II reaction. Type I reaction involves electron transfer from triplet state PS to an organic substrate within the cells, leading to the production of free radicals. These free radicals interact with oxygen at a molecular level and produce reactive oxygen species (ROS) such as superoxide, hydroxyl radicals and hydrogen peroxide. These oxidizing molecules potentially react with bacterial biomolecules and inhibit them. In the type II reaction, energy transfer occurs between the excited PS and the ground state molecular oxygen, producing singlet oxygen that can interact with a large number of molecules in the cell to generate oxidized products [13,14]. Compared to other antibacterial modalities, aPDT has the advantage that bacteria rarely develop resistance to ROS [15].

Antibacterial photodynamic therapy uses either red light (630–700 nm) or blue light (380–500 nm) as a light source [16]. Conventional PDT using red light [17] has some drawbacks; the increased risk of thermal injury to oral tissues [18], the risk of tooth discoloration following application of phenothiazine dyes [19,20]. Moreover, red light sources with corresponding photosensitizer’s absorption wavelengths are expensive and are not commonly available in dental offices [16]. On the other hand, blue light used in modified aPDT using a LED source [17] has minor thermal effects on host tissues [19]. In addition, all dental offices own blue light sources for curing composite resin materials [21,22]. However, the selection of photosensitizers with absorption wavelengths matching that of blue light is mandatory for successful results [16]. Currently, photosensitizers such as rose bengal, hypericin, porphyrin, fullerenes and flavin derivatives have been tested in-vitro settings but the results have still not been translated clinically. One of these blue light-sensitive photosensitizers is curcumin [23].

Curcumin, an ecofriendly naturally driven product extracted from roots of Curcuma Longa (turmeric) [24,25], has been the subject of interest for much research due to its excellent photodynamic activity [26]. Moreover, it has several pharmacological effects such as anti-inflammatory activities, antioxidant, bactericidal, antifungal and analgesic effects. Furthermore, curcumin appears to inhibit mecA gene transcription, resulting in lower penicillin-binding protein 2a (PBP2a) expression, which allows ß-lactam antibiotics to act more efficiently [27].

However, curcumin is known for its inherent hydrophobicity. Being water insoluble, different solvents are used for its dissolution such as dimethyl sulfoxide (DMSO) [28]. DMSO, which has a foul odor, has been shown to cause drastic effects on cellular processes and extreme changes in miRNA. This may be a threat, when it affects developmentally significant genes, and have detrimental effects later in life or perhaps in future generations [29]. Additionally, a major drawback of the phototherapeutic treatments currently used for root canal disinfection is the limited penetration of a photosensitizer. Higher photosensitizer per mass content could be achieved when photosensitizer is used in the nano-scale (1 to 100 nm in size) or conjugated with nanoparticles, leading to higher reactive oxygen species production [30]. This may further enhance its antibacterial properties, and may overcome curcumin hydrophobicity as well as improve its penetration into dentinal tubules [31].

Therefore, the objective of the current study was to prepare, characterize and test the antibacterial activity of nanocurcumin photosensitizer to be used for aPDT in endodontics. Furthermore, its penetration into dentinal tubules was assessed when compared to both curcumin and methylene blue as the control photosensitizer.

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