Safety assessment of Paeonia lactiflora root extract for a cosmetic ingredient employing the threshold of toxicological concern (TTC) approach.

Botanical extracts, widely used in cosmetics, pose a challenge to safety assessment due to their complex compositions. The threshold of toxicological concern (TTC) approach, offering a safe exposure level for cosmetic ingredients, proves to be a promising solution for ensuring the safety of cosmetic ingredients with low exposure level. We assessed the safety of Paeonia lactiflora root extract (PLR), commonly used in skin conditioning products, with the TTC. We identified 50 constituents of PLR extract from the USDA database and literature exploration. Concentration of each constituent of PLR extract was determined with the information from USDA references, literature, and experimental analysis. The genotoxicity of PLR and its constituents was assessed in vitro and in silico respectively. Cramer class of the constituents of the PLR extract was determined with Toxtree 3.1 extended decision tree using ChemTunes®. Systemic exposure of each constituent from leave-on type cosmetic products containing PLR at a 1% concentration was estimated and compared with respective TTC threshold. Two constituents exceeding TTC threshold were further analyzed for dermal absorption using in silico tools, which confirmed the safety of PLR extract in cosmetics. Collectively, we demonstrated that the TTC is a useful tool for assessing botanical extract safety in cosmetics.

Safety assessment of Cnidium officinale rhizome extract in cosmetics using the Threshold of Toxicological Concern (TTC) approach.

Cosmetics often contain botanical extracts, which present a challenge for safety assessors due to their complex composition. The threshold of toxicological concern (TTC) approach is considered as a solution for the safety assessment of botanical extracts in cosmetics as part of next-generation risk assessment. In this study, we applied the TTC approach to evaluate the safety of Cnidium officinale rhizome extract (CORE), a widely used botanical extract in skin conditioning products. We identified 32 components of CORE through the USDA database and literature and determined the content of each component through literature or actual analysis where an authentic standard was available. Macro- and micronutrients were also analyzed to exclude them as safe components. The Toxtree® software was used to identify the Cramer class of remaining components. We estimated the systemic exposure of each component from leave-on type cosmetic products containing CORE at a 1% concentration and compared the results to TTC thresholds. All components of CORE had a systemic exposure below the TTC threshold. While batch variations and presence of unknown chemicals in individual CORE materials should be considered, this study demonstrated that the TTC approach can be a useful tool for the safety assessment of botanical extracts in cosmetics.

Improved stability and skin permeability of sodium hyaluronate-chitosan multilayered liposomes by Layer-by-Layer electrostatic deposition for quercetin delivery.

Layer-by-Layer (LbL) technology, based on the electrostatic interaction of polyelectrolytes, is used to improve the stability of drug delivery systems. In the present study, we developed multilayered liposomes with up to 10 alternating layers based on LbL deposition of hyaluronate-chitosan for transdermal delivery. Dihexadecyl phosphate was used to provide liposomes with a negative charge; the liposomes were subsequently coated with cationic chitosan (CH) followed by anionic sodium hyaluronate (HA). The resulting particles had a cumulative size of 528.28±29.22nm and an alternative change in zeta potential. Differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) revealed that the multilayered liposomes formed a spherical polyelectrolyte complex (PEC) after deposition. Observations in size distribution after 1 week found that the particles coated with even layers of polyelectrolytes, hyaluronate and chitosan (HA-CH), were more stable than the odd layers. Membrane stability in the presence of the surfactant Triton X-100 increased with an increase in bilayers as compared to uncoated liposomes. An increase in the number of bilayers deposited on the liposomal surface resulted in a sustained release of quercetin, with release kinetics that fit the Korsmeyer-Peppas model. In an in vitro skin permeation study, negatively charged (HA-CH)-L and positively charged CH-L were observed to have similar skin permeability, which were superior to uncoated liposomes. These results indicate that multilayered liposomes properly coated with polyelectrolytes of HA and CH by electrostatic interaction improve stability and can also function as potential drug delivery system for the transdermal delivery of the hydrophobic antioxidant quercetin.