Combination of UVB Absorbing Titanium Dioxide and Quercetin Nanogel for Skin Cancer Chemoprevention

Sunscreens are widely prescribed and used to prevent skin cancer; however, they have been reported to contain various chemicals which mimic hormones and disrupt hormonal functioning in humans. The aim of this study was to develop topical nanogel for skin cancer prevention using an antioxidant compound quercetin (Qu) and inorganic titanium dioxide (TiO2). Two formulations of Qu nanocrystals were optimized with low and high concentration of drug using the Box-Behnken design with the quadratic response surface model and further homogenized with TiO2. Qu nanocrystal (0.08% and 0.12%) formulations showed a particle size of 249.65 +/- 2.84nm and 352.48 +/- 3.56nm with zeta potential of -14.7 +/- 0.41mV and -19.6 +/- 0.37mV and drug content of 89.27 +/- 1.39% and 90.38 +/- 1.81% respectively. Scanning electron microscopy (SEM) images showed rod-shaped nanocrystals with a particle size below 400nm. Qu (0.08%), Qu (0.12%), Qu (0.12%)+TiO2 (5%), and Qu (0.12%)+TiO2 (15%) nanogels showed over 70% drug release with significantly (p<0.001) enhanced skin deposition of Qu as compare with Qu suspension within 24h. The average numbers of tumor, tumor volume, and percentage of animals with tumors at onset in the Qu (0.12%)+TiO2 (15%) nanogel-pretreated group was found to be significantly (p<0.05) less as compared with the UV only exposed group. Further, Qu (0.12%)+TiO2 (15%) nanogel significantly (p<0.001) downregulated COX-2, EP3, EP4, PCNA, and cyclin D1 expressions in contrast to Qu and TiO2 only pretreated groups. Therefore, novel combination of Qu (0.12%)+TiO2 (15%) with enhanced skin deposition can be used as a chemopreventive strategy in UVB-induced skin photocarcinogenesis.