Carbamide peroxide nanoparticles for dental whitening application: Characterization, stability and in vivo/in situ evaluation
Graphical abstract
Introduction
Carbamide peroxide (CP) is a hydrogen peroxide derivative bonded with urea, known also as urea hydrogen peroxide. This active is extensively used as a green oxidizing agent in organic synthesis and as disinfecting, antiseptic or bleaching agent in cosmetics and pharmaceutical industries [1,2]. The CP material safety data sheet (MSDS) describes this raw material as an oxidizing and corrosive agent [2]. The CP used in home whitening products, without a dentist monitoring at moment of the time application, is the most popular method for obtaining whiter teeth, the technique involves the application of a whitening gel in a custom-fitted soft plastic tray to the patient for home use [1,[3], [4], [5]]. The bleaching agents action mechanism is similar among the CP agents, with those containing hydrogen peroxide decomposing in water and oxygen, which diffuses through the enamel organic matrix and dentin, releasing water and the free radical O2⋅. The great oxidative power of the released free radical causes the oxidation of macromolecular chromogenic organic pigments in smaller molecules; these simple molecules reflect more light and, thus, the bleaching effect [1,[6], [7], [8]].
Due to their chemical nature, bleaching agents are unstable. Studies have reported that these agents presented degradation in bleaching teeth products, decreasing the content designated on the label and the concentration required for its effective action, which compromises the efficacy and bleaching quality [6,9,10]. Regardless of the type, concentration or presentation form, bleaching agents are sensitive under certain storage conditions, losing their potency over time when exposed to factors such as light, heat or environmental adversity. Because of these factors, package information should recommend the storage at low temperatures, aiming the protection against light, moisture, and impurities since degradations are as faster as temperature increases. Hence, oxidizable substances should be stored in a cool place [[11], [12], [13]].
Nanotechnology is applied to develop and produce nanometer-scale material, covering the delivery of active principles, called nanodelivery systems. These systems include nanoemulsions, polymeric nanoparticles (nanospheres or nanocapsules) and liposomes [[14], [15], [16]]. The resultant systems could increase the clinical efficacy due to the ultrasmall size, large surface area, solubility, permeability, site-specific delivery, decreased adverse effects and control release [14,15]. A new alternative for CP stabilization is the use of polymeric nanoparticles, mainly the systems are biocompatible and biodegradable system. Nanoparticles are formed by carrier systems lower than 1 μm in size that could stand out due to the ability to stabilize therapeutic active agents during storage, in the application in pharmaceutical form and to control their release [16,17]. The nanotechnology has been used in odontology for many kinds of applications. Bioadhesive nanoparticles for oral cavity application have been shown to have the potential to further improve stability in this environment [18]. The literature reports the growing use of nanomaterial in dentistry [19,20] and the majority of applications were directed to the control of dental caries [21], dentin hypersensitivity or remineralization [22,23]. However, to our knowledge, there are no studies using nanomaterials in teeth bleaching applications.
Considering these developments, the present study aimed to evaluate the CP nanoparticles for application in dental bleaching. After characterization of the nanoparticles, comparative stability studies were conducted to verify if the CP carrier provided an improvement in stability and in vivo efficacy, and in situ histological analyses of pulp damage were performed to ensure product safety.
Section snippets
Materials
CP was purchased from Sigma-Aldrich (Saint Luis, USA). Potassium iodide and ammonium molybdate were purchased from Synth (São Paulo, Brazil). Glacial acetic acid was purchased from Maia (São Paulo, Brazil). Ultra-purified water, used to prepare all solutions, was obtained from a Milli-Q gradient system (Millipore, USA). The CP polymeric nanoparticles and blank nanoparticles were purchased from Nanovetores SA (Florianopolis, Brazil), nanoparticles developer and producer (the characterization,
Carbamide peroxide nanoparticle characterization
The nanoparticles presented a bimodal population size, P1, with 11.22 ± 3.62 nm, and P2, with 398.3 ± 22.90 nm, with predominance of the P1 size (77%), average size of 13.35 ± 0.26 and polydispersity index was 0.38 ± 0.007. The CP content was 27.67% ± 0.05. Both populations could be confirmed with TEM photomicrographs, observed in Fig. 1. In accordance with the literature, polymeric nanoparticle systems have been described in the size range of 50–615 nm [15]. The bimodal distribution was also
Conclusions
The present study demonstrated that a technological strategy a nanostructured carrier system using polymer nanoparticles as carbamide peroxide delivery have advantages. The stability studies of nanoparticles revealed the improved stability of the developed system when compared active free. The results obtained on the characterization suggest that the stabilization of the nanoparticles occurs through a steric effect, since the zeta potential is low. The efficacy of bleaching gels containing the
Ethics approval and consent to participate
Humans were used for part of this research and it was approved by the Ethics Committee on Research with Human Beings (CEPSH) of the Federal University of Santa Catarina (UFSC), at the number 33292314.6.0000.0121.
Conflict of interest
The authors have no conflict of interest rather than article.
Acknowledgements
The authors would like to thank FAPESC (Fundação de Amparo a Pesquisa do Estado de Santa Catarina) for financial support (TECNOVA). The authors thank the laboratory of the Nucleus of Research in Ceramic and Composites of the Department of Mechanical Engineering of UFSC (CERMAT) of UFSC for equipment used, the Zetasizer Nano ZS (Malvern Instruments, Worcestershire, UK). The authors thank the Electronic Microscopy Laboratory (LCME) at UFSC for photomicrographs done using TEM. The authors thank
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