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

AAPS PharmSciTech volume 20, Article number: 240 (2019) Cite this article

Abstract

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 ± 2.84 nm and 352.48 ± 3.56 nm with zeta potential of − 14.7 ± 0.41 mV and − 19.6 ± 0.37 mV 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 400 nm. 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 24 h. 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.

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Funding

This project was funded by the Specialized Program of Research Excellence (SPORE) a subaward from Moffett Cancer Center (4 P5O CA168536-04, NIH), and National Institute on Minority Health and Health Disparities (NIMHD) P20 program (Grant # IP20MD006738-03 to M.S.)

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Affiliations

  1. College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 1520 S Martin Luther King Jr. Blvd, Tallahassee, Florida, 32307, USA

    Arvind Bagde, Arindam Mondal, Shallu Kutlehria, Aragaw Gebeyehu, Nilkumar Patel & Mandip Singh

  2. College of Pharmacy and Health Sciences, St. John’s University, Queens, New York, New York, 11439, USA

    Ketan Patel

  3. College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana, 70125, USA

    Nusrat Chowdhury

  4. H. Lee Moffitt Cancer Center and Research Institute, Inc., Tampa, Florida, USA

    Nagi Kumar

Authors
  1. Arvind Bagde
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  2. Ketan Patel
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  6. Aragaw Gebeyehu
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  7. Nilkumar Patel
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  9. Mandip Singh
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Correspondence to Mandip Singh.

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Bagde, A., Patel, K., Mondal, A. et al. Combination of UVB Absorbing Titanium Dioxide and Quercetin Nanogel for Skin Cancer Chemoprevention. AAPS PharmSciTech 20, 240 (2019). https://doi.org/10.1208/s12249-019-1424-x

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  • DOI: https://doi.org/10.1208/s12249-019-1424-x

KEY WORDS

  • topical delivery
  • skin cancer chemoprevention
  • nanogel
  • quercetin
  • titanium dioxide