LLY507 br celecoxib cytotoxicity Compared to potent
celecoxib cytotoxicity. Compared to potent cytotoxic drugs like pacli-taxel and doxorubicin, the obtained celecoxib IC50 was high, and jus-tifies its intended use to alter other pathways involved in cancer de-velopment (Carvalho et al., 2017b; Elmets et al., 2010; Fischer et al., 1999). Celecoxib incorporation in ME-60 reduced its IC50, an eﬀect generally attributed to a more eﬃcient drug delivery into LLY507 and/or increased solubility of lipophilic drugs in the aqueous culture medium (Migotto et al., 2018; Pepe et al., 2016; Stover and Kester, 2003). However, the fact that ME-60 droplet size increased when it was diluted in the cell culture medium, suggests some sort of formulation destabi-lization, and that (i) the increased cytotoxicity might result from the combined eﬀects of the drug and formulation components and not necessarily from the intact microemulsion-mediated delivery, and (ii) presence of formulation components in the mammary tissue might aid drug cytotoxicity. We do not expect ME-60 to cross the skin intact, but because of the ability to puncture the skin, microneedle application might improve the amount of microemulsion components reaching the mammary tissue, and thus, aid drug cytotoxic eﬀects against cancer cells. Future studies will focus on assessing celecoxib eﬀect on COX-2 in vivo.
Our results demonstrate that microemulsion optimization was es-sential to combine enhancement of celecoxib penetration and for-mulation safety, and support the combination of ME-60 with micro-needles to further improve celecoxib delivery. With this study, we hope to contribute to the development of an eﬀective, well accepted and much needed local strategy for chemoprevention of breast cancer.
This study was supported by São Paulo Research Foundation (FAPESP, grant# 2013/16617-7) and National Counsel of Technological and Scientific Development (CNPq, grant# 443549/ 2014-1). Fellowships from PIBIT/CNPq (to G. Mojeiko) and FAPESP (grant# 2017/23213-0 to G.C. Salata) are greatly appreciated. The authors would like to thank Dr. Leticia Costa-Lotufo (Institute of Biomedical Sciences, University of Sao Paulo) for use of the cell culture facility.
Appendix A. Supplementary data
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