Title : Design and optimization of a nanotechnological platform for future delivery of Sarcomphalus joazeiro (Mart.) extract in dental bleaching
Abstract:
Although effective in removing stains from teeth, peroxides can trigger severe side effects, such as gum inflammation and dental hypersensitivity, due to free radical penetration into dentinal tubules. In this scenario, Sarcomphalus joazeiro stands out as a promising alternative; its bark extract is rich in saponins acting as triterpenic biosurfactants with intrinsic whitening potential and detergent/emulsifying properties, removing residues without causing oxidative stress or reducing pH. However, conventional formulations release active compounds on the tooth surface, failing to penetrate the enamel's interprismatic spaces (0.1 µm). Since plant extracts comprise a complex matrix with components of varying polarities, an oil-in-water (O/W) microemulsion (10–100 nm) represents an ideal nanotechnology platform to encapsulate these molecules and facilitate their permeation into the internal dental structure safely. Therefore, this study aimed to develop and optimize an O/W microemulsion to deliver S. joazeiro extract for future dental applications. A D-optimal Mixture Design (DoE) was used via Design Expert® software to define the proportions of Myritol® 312 LB, water, and surfactants (Kolliphor® RH 40 and Span® 80). The surfactant ratio was fixed at 37.3% Span® 80 and 62.7% Kolliphor® RH 40 to match the required hydrophilic-lipophilic balance (rHLB) of the oily phase. Consequently, twenty-four pseudo-random formulations were produced using a low-energy method under magnetic stirring (organic phase at 50 °C, 500 rpm, followed by dropwise addition of the aqueous phase). After 48 hours, the dependent variables were obtained through the analysis of droplet size and polydispersity index (PdI) via dynamic light scattering (DLS) using a ZetaSizer NanoZS (1:400 v/v dilution in purified water). Beyond these variables, the optimized formulation (MEMY) was also analyzed for transmittance via UV-Vis spectrophotometry set at 650 nm to evaluate translucency. Following ANOVA for each dependent variable, the models were applied in the optimization stage to select points with a droplet size < 50 nm. The optimized formulation was replicated in triplicate. The droplet size ANOVA was highly significant (p < 0.05) with no lack of fit (p > 0.05), displaying a model F-value of 90.06, lack of fit F-value of 0.348, adjusted R² of 0.973, and predictive R² of 0.957. Hence, the adequate precision value was 26.911, is minimum of 4, proving model reliability. Conversely, the PdI model lacked statistical significance (model F-value of 1.45, p = 0.259, adjusted R² of 0.039, adequate precision < 4) and was excluded from optimization criteria. Subsequently, graphical optimization generated an overlay chart based on the 50 nm threshold, from a theoretical point was selected. The MEMY formulation presented an ideal average hydrodynamic droplet size of 30.84 d.nm ± 1.53, a monodisperse profile (PdI 0.071 ± 0.006), and high transmittance (86.92% ± 7.18), characteristic of microemulsified systems. This experimental design proved highly effective in modeling a microemulsified platform, establishing a viable nanocarrier for future delivery of S. joazeiro extract in safe dental whitening.
