SURFACTANT PENETRATION 105 pore radius/number density could play an important role in skin barrier protection. Bind- ing surfactants with other bulky molecules such as nonionic surfactants and polymers is one of the common methods to increase surfactant micelle size (62). For example, mixing C12E6 with SDS reduces SDS CMC and induces its micelle growth (63), thereby limit- ing SDS monomer and micelle skin penetration and reducing SDS-induced skin irritation. In the experiments directed by Moore et al. (50), Polyethylene oxide (PEO) was mixed with SDS in solution. Hydrophilic polymers like PEO are known to form micelle-like complexes with anionic surfactants such as SDS, with the polymer forming a corona around the anionic surfactant micelles. An obvious increase in the average SDS micelle radius from 20 to 25 A was observed with the addition of PEO. This binding effectively reduced SDS skin penetration attributed to the steric hindrance and/or the slow diffusion of SDS. Adding humectant to the surfactant solution is known to improve the skin mildness by providing hydration (64,65). Ghosh and Blankschtein (66) demonstrated that it is also an effective way to reduce surfactant penetration. In their study (66), electrical currents served as an index to refl ect the amount of SDS presented in the skin barrier. The results indicated that the amount of SDS in the skin continuously increased when the pure SDS concentration exceeded the CMC. However, it was not the case for the mixture of SDS in 10% glycerol solution. Ghosh and Blankschtein (66) stated three hypothesizes to account for the reduced SDS penetration by adding 10% glycerol: (i) the glycerol addition reduced the SDS CMC (ii) the addition of the 10% glycerol increased the SDS micelle size, hindering them from penetrating into the skin (iii) 10% glycerol reduced the radius and/or the density of the aqueous pores in the skin barrier. Both (i) and (ii) hypotheses were proved to be invalid. The data in Table VI demonstrated that the 10% glycerol addition effectively reduced the average pore radius and the pore number density in the skin. Table V CMCs, Micelle Diameter, and Zeta Potential of 16 Surfactant Systems Tested by 14 C-SDS Surfactant system CMC, mM Micelle diameter, nm Zeta potential, mV SLS 3.15 ± 0.03 2.73 ± 0.19 -54.1 ± 3.8 SLS in NaCl (0.01 M) 2.64 ± 0.31 3.43 ± 0.16 — SLS in NaCl (0.05 M) 1.43 ± 0.12 4.86 ± 0.26 — SLS in NaCl (0.10 M) 1.06 ± 0.07 5.51 ± 0.15 — SLS in NaCl (0.25 M) 0.671 ± 0.0015 0.628 ± 0.06 — SLS with 2% PEO 2.30 ± 0.18 3.04 ± 0.12 -24.2 ± 0.7 SLS with Dimethyl dodecyl amine oxide 4.86 ± 0.22 126 ± 20 -77.5 ± 3.6 SLS with Lauramidopropyl betaine 0.526 ± 0.032 4.10 ± 0.30 -52.9 ± 6.5 SLS with Lauric acid 9.26 ± 0.08 2.26 ± 0.10 -72.7 ± 4.1 Sodium dodecyl benzene sulphonate 2.00 ± 0.08 3,94 ± 0.07 -47.9 ± 5.1 SLE1 S 1.32 ± 0.04 2.26 ± 0.15 -46.1 ± 4.5 SLE3S 0.452 ± 0.037 2.19 ± 0.06 -27.6 ± 2.3 SLI with LAPB 0.289 ± 0.023 4.07 ± 0.41 -63.0 ± 6.3 C12E6 0.0695 ± 0.0014 25.3 ± 1.1 -7.2 ± 0.9 SLS with C12E5 0.0993 ± 0.0022 1.85 ± 0.06 -39.4 ± 4.7 SLS with C12E6 0.0992 ± 0.0034 1.91 ± 0.17 -32.5 ± 1.4

JOURNAL OF COSMETIC SCIENCE 106 CONCLUSION AND PERSPECTIVES The focus of this article is to summarize the state-of-the-art understanding of surfac- tants’ penetration into the skin, which have been studied by many researchers for decades. Nevertheless, an explicit surfactant penetration model still could not be given so far. It is likely that different penetration hypotheses play a role simultaneously, and a combi- nation of all the mechanisms enables surfactant penetration into the skin. With respect to mild cleansing, the addition of nonionic/amphoteric surfactants, hydrophilic polymers, or humectants such as glycerol can minimize the skin penetration of anionic surfactants, reducing the occurrence of skin irritation. On the other hand, a complete prevention of surfactant penetration into the skin is diffi cult and challenging, implying that surfactants can be used as penetration enhancers for transepidermal-active delivery. ACKNOWLEDGMENTS The author is grateful for the opportunities provided by the College of Pharmacy, Shenyang Pharmaceutical University, and the ViaX Online Education. REFERENCES (1 ) K. Holmberg, B. Jönsson, B. Kronberg, and B. Lindaman, “Introduction of surfactants,” in Surfactants and Polymers in Aqueous Solution, 2nd Ed., John Wiley & Sons Ltd., (2002), pp. 1–23. (2) A. Mehling, M. Kleber, and H. Hensen, Comparative studies on the ocular and dermal irritation poten- tial of surfactants. Food Chem. Toxicol., 45, 747–758 (2007). (3) Y. Nakama, “Sufactants,” in Cosmetic Science and Technology, 1st Ed., Elsevier Ltd., (2017), pp. 231–224. (4 ) A. Seweryn, Interactions between surfactants and the skin – theory and practice, Adv. Colloid Interf. Sci., 256, 242–255 (2018). ( 5) L. Zhang, X. Zhang, P. Zhang, Z. Zhang, S. Liu, and B. Han, Effi cient emulsifying properties of glyc- erol-based surfactant, Colloids Surf. A, 553, 225–229 (2018). (6 ) P. López-Mahía, S. Muniategui, D. Prada-Rodríguez, and M. C. Prieto-Blanco, “Surfactants and deter- gents,” in Encyclopedia of Analytical Science, 2nd Ed. Elsevier Ltd., (2005), pp. 554–561. (7) D. Bajpai, A. Mishra, J. Clark, T. Farmer, Synthesis, chemistry, physicochemical properties and indus- trial applications of amino acid surfactants: a review, Compt. Rendus Chem., 21, 112–130 (2018). (8) Y . Yu, J. Zhao, and A. E. Bayly, Development of surfactants and builders in detergent formulations. Chin. J. Chem. Eng., 16(4), 517–527 (2008). (9) J . Steber, “The ecotoxicity of cleaning product ingredients.” in Handbook for Cleaning/Decontamination of Surfaces., 1st Ed., Elsevier B.V, (2007), Vol. 2, pp. 721–746. (10) D . Zhao and Y. Wan, The synthesis of mesoporous molecular sieves. Stud. Surf. Sci. Catal., 168, 241– 300 (2007). (11) M . Teresa Garcia, E. Campos, A. Marsal, and I. Ribosa, Fate and effects of amphoteric surfactants in the aquatic environment, Environ. Int., 34, 1001–1005 (2008). Table VI Skin Aqueous Pore Radius and Normalized Pore Number Density Resulted by Various Solutions Solution Average pore radius, rpore (A) Normalized pore number density, (ε/τ)normal SDS 33 ± 5 7 ± 1 SDS with 10% glycerol 20 ± 5 3 ± 1 PBS control 20 ± 3 1 10% glycerol 11 ± 4 0.5 ± 0.1 See references 68., 69., 70., 71., 72., 73.