br Appendix A Supplementary data br References br T Zhang
Appendix A. Supplementary data
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J. Chang, B. Zhang, Albumin-bioinspired Gd:CuS nanotheranostic agent for in vivo photoacoustic/magnetic resonance imaging-guided tumor-targeted photothermal therapy, ACS Nano 10 (2016) 10245–10257.  L. Li, L.H. Rashidi, M. Yao, L. Ma, L. Chen, J. Zhang, Y. Zhang, W. Chen, CuS nanoagents for photodynamic and photothermal therapies: phenomena and pos-sible mechanisms, Photodiagnosis Photodyn. Ther. 19 (2017) 5–14.
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International Journal of Pharmaceutics
journal homepage: www.elsevier.com/locate/ijpharm
Combination of microneedles and microemulsions to increase celecoxib topical delivery for potential application in chemoprevention of breast cancer
Gabriela Mojeiko, Moacir de Brito, Giovanna C. Salata, Luciana B. Lopes
Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Brazil
In spite of the high incidence of breast cancer worldwide, there are few strategies for its chemoprevention, and they have limited adherence mainly due to their serious adverse eﬀects. As a new approach for local breast cancer chemoprevention, we developed and optimized microemulsions for topical delivery of celecoxib to the breast skin, and evaluated their combination with microneedles to improve drug penetration for localization in the mammary tissue. Microemulsions containing water at 15% (ME-15), 29% (ME-29) and 60% (ME-60) were obtained and characterized. They were isotropic, displayed Newtonian behavior and particle size smaller than 100 nm. ME-15 and ME-29 increased transepidermal water loss (TEWL) compared to ME-60, and displayed stronger vascular toxicity, evidenced by hemorrhage and lysis in HET-CAM assays. ME-60 was more eﬃcacious at increasing celecoxib cutaneous and percutaneous delivery (1.3–4-fold). Increasing the number of microneedle roller applications from 1 to 8 increased the number of skin punctures and TEWL; its association with ME-60 promoted no further increase in TEWL, but improved (1.6–4-fold) celecoxib cutaneous and percutaneous de-livery. Microemulsion incorporation reduced celecoxib IC50 in MCF-7 cells (3.3-fold), suggesting that presence of formulation components in the mammary tissue might improve drug cytotoxicity.
Breast cancer is the most incident malignancy for women in both high- and low-income regions, with an estimated number of cases in 2012 of 1.7 million (Ferlay et al., 2015; Kwa et al., 2017). Considering population aging, obesity, and advances in screening techniques, the incidence is destined to increase (Blucher and Stadler, 2017). New strategies for treatment have been studied along the years, including targeted drug delivery and local treatment of in situ carcinoma, but chemoprevention strategies have not received pronounced attention (Migotto et al., 2018; Naz et al., 2017; Pedrosa et al., 2015).