PHARMACEUTICALLY OPTIMIZED TOPICAL NANOGEL FORMULATION 61 ACKNOWLEDGMEN TS This study wa s supported by a research grant from Ege University (15-ECZ-005). We would like to acknowledge E.U. Pharmaceutical Sciences Research Center (FABAL) for enabling us to use its laboratory instruments. REFERENCES ( 1) M. P. Lu p o, Antioxidants and vitamins in cosmetics, Clin. Dermatol., 19(4), 467–473 (2001). (2) P. Ratta n awiwatpong, R. Wanitphakdeedecha, A. Bumrungpert, and M. Maiprasert, Anti-aging and brightening effects of a topical treatment containing vitamin C, vitamin E, and raspberry leaf cell cul- ture extract: a split-face, randomized controlled trial, J. Cosmet. Dermatol., 19, 671–676 (2020). (3) A. M. Ma i a, A. R. Babya, W. J. Yasaka, E. Suenaga, T. M. Kaneko, and M. V. R. Velasco, Validation of HPLC stability-indicating method for vitamin C in semisolid pharmaceutical/cosmetic preparations with glutathione and sodium metabisulfi te, as antioxidants, Talanta, 71, 639–643 (2007). (4) A. Chiu a nd A. B. Kimball, Topical vitamins, minerals and botanical ingredient as modulators of envi- ronmental and chronological skin damage, Br. J. Dermatol., 149, 681–691 (2003). (5) C. L. Ph i llips, S. Tajima, and S. R. Pinnel, Ascorbic acid and transforming growth factor-ß1 increase collagen biosynthesis via different mechanisms: coordinate regulation of pro-alpha 1(I) and pro-alpha 1(III) collagens, Arch. Biochem. Biophys., 295, 397–403 (1992). (6) J. C. Gee s in, D. Darr, R. Kaufman, S. Murad, and S. R. Pinnell, Ascorbic acid specifi cally increases type I and type III procollagen messenger RNA levels in human skin fi broblast, J. Invest. Dermatol., 90, 420–424 (1988). (7) J. M. Pul l ar, A. C. Carr, and M. C. M. Vissers, The roles of vitamin C in skin health, Nutrients, 9, 866 (2017). (8) P. K. Vem u la, U. Aslam, V. Ajay Mallia, and G. John, In situ synthesis of gold nanoparticles using mo- lecular gels and liquid crystals from vitamin-C amphiphiles, Chem. Mater., 19(2), 138–140 (2007). (9) B. Rozman , A. Zvonar, F. Falson, and M. Gasperlin, Temperature-sensitive microemulsion gel: an effec- tive topical delivery system for simultaneous delivery of vitamins C and E, AAPS PharmSciTech, 10(1), 54–61 (2009). (10) J. H. Ya n g, S. Y. Lee, Y. S. Han, K. C. Park, and J. H. Choy, Effi cient transdermal penetration and im- proved stability of L-ascorbic acid encapsulated in an inorganic nanocapsule, Bull. Korean Chem. Soc., 24(4), 499–503 (2003). (11) Z. Jiao, X. Wang, Y. Yin, and J. Xia, Preparation and evaluation of vitamin C and folic acid-coloaded antioxidant liposomes, Part. Sci. Technol., 37(4), 453–459 (2019). (12) D. Li, C . F. van Nostrum, E. Mastrobattista, T. Vermonden, and W. E. Hennink, Nanogels for intracel- lular delivery of biotherapeutics, J. Contr. Release 259, 16–28 (2017). (13) A. V. Kab a nov and S. V. Vinogradov, Nanogels as pharmaceuticals carriers: fi nite networks of infi nite capabilities. Angew. Chem. Int. Ed. Engl. 48(30), 5418–5429 (2009). (14.) S. Rençbe r , S. Y. Karavana, F. F. Yılmaz, B. Eraç, M. Nenni, S. Özbal, Ç. Pekçetin, H. Gurer Orhan, M. Hoşgör Limoncu, P. Güneri, and G. Ertan. Development, characterization and In Vivo assessment of mucoadhesive nanoparticles containing fl uconazole for the local treatment of oral candidiasis, Int. J. Nanomed., 11, 2641–2653 (2016). (15) Y. Wanga, S. Xuc, W . Xionga, Y. Pei, B. Li, and Y. Chen, Nanogels fabricated from bovine serum albu- min and chitosan via self-assembly for delivery of anticancer drug, Colloids Surf. B: Biointerfaces, 146, 107–113 (2016). (16) G. Sandri, S. Rossi , F. Ferrari, M. C. Bonferonia, C. Muzzarelli, and C. Caramella, Assessment of chitosan derivatives as buccal and vaginal penetration enhancers. Eur. J. Pharmaceut. Sci., 21, 351– 359 (2004). (17) J. Y. Chang, Y. K. O h, H. S. Kong, E. J. Kim, D. D. Jang, K. T. Nam, and C. K. Kim, Prolonged an- tifungal effects of clotrimazole-containing mucoadhesive thermosensitive gels on vaginitis, J. Contr. Release, 82(1), 39–50 (2002). (18) M. Mathew and S. Su b ramanian, In vitro screening for anti-cholinesterase and antioxidant activity of methanolic extracts of ayurvedic medicinal plants used for cognitive disorders, PLoS One, 9(1), e86804 (2014). (19) T. Şenyiğit, F. Son v ico, S. Barbieri, Ö. Özer, P. Santi, and P. Colombo, Lecithin/chitosan nanoparticles of clobetazol-17-propionate capable of accumulation in pig skin, J. Contr. Release, 142(3), 368–373 (2010).

JOURNAL OF COSMETIC SCIENCE 62 (20) C. Yohannan Panicker, H. Tresa Varghese, and D. Philip, FT-IR, FT-Raman and SERS spectra of vita- min C, Spectrochim. Acta Mol. Biomol. Spectrosc., 65(3-4), 802–804 (2006). (21) K. E. Burke, Mechanisms o f aging and development-a new understanding of environmental damage to the skin and prevention with topical antioxidants. Mech. Ageing Dev., 172, 123–130 (2018). (22) M. P. Lupo, Antioxidants and vitamins in cosmetics, Clin. Dermatol., 19(4), 467–473 (2001). (23) P. Saokar Telang, Vitami n C in dermatology. Indian Dermatol. Online J., 4(2), 143–146 (2013). (24) A. Shayan, A. Khair, and M. Nathalie, Advancement in nanogel formulations provides controlled drug release, Int. J. Pharm, 584(30), 119435 (2020). (25) B. A. Aderibigbe and T. N aki, Design and effi cacy of nanogels formulations for intranasal administra- tion, Molecules, 23(6), 1241 (2018). (26) P. Islam, J. J. Water, A . Bohr, and J. Rantanen, Chitosan-based nano-embedded microparticles: impact of nanogel composition on physicochemical properties. Parmaceutics, 9(1), 1–12 (2017). (27) International Conference on Harmonisation (ICH) (2005) [Online] http://www.ich.org/LOB/media/ MEDIA417.pdf. (28) J. Y. Jun, H. H. Nguyen, S. Y. R. Paik, H. S. Chun, B. C. Kang, and S. Ko, Preparation of size- controlled bovine serum albumin (BSA) nanoparticles by a modifi ed desolvation method, Food Chem., 127, 1892–1898 (2011). (29) I. Lee and K. Akiyoshi, S ingle molecular mechanics of a cholesterol-bearing pullulan nanogel at the hydrophobic interfaces, Biomaterials, 25(15), 2911–2918 (2004). (30) D. J. Mastropietro, R. N i mroozi, and H. Omidian, Rheology in pharmaceutical formulations-a perspec- tive, J. Dev. Drugs, 2(2), 1–6 (2013). (31) K. A. Wadile, P. P. Ige, and R. O. Sonawane, Preparation of itraconazole nanoparticles and its topical nanogel: physicochemical properties and stability studies, Int. J. Pharm. Sci. Dev. Res., 5(1), 1–8 (2019). (32) S. Güngör, M. S. Erdal, a nd Y. Özsoy, Plasticizers in transdermal drug delivery systems, Recent Adv. Plast., 5, 91–112 (2012).