Considering the high incidence of skin and breast tumors and the unavailability of strategies to localize drugs in these tissues while avoiding systemic exposure and side effects, we propose the development of cationic nanocarriers for topical delivery of chemopreventive and chemotherapeutic agents. Because tumor development and progression are multifactorial, the co-incorporation of compounds capable of interfering with multiple signaling cascades may potentiate each other effects' and improve the efficacy of the treatment. Based on these facts, we propose to combine agents that exhibit anti-proliferative, cytotoxic and estrogen receptor-modulating activity in cationic microemulsions. Cationic amphiphilic peptides that are able to penetrate across biological barriers will be added to the system to impart the positive charge and facilitate the translocation of active compounds across biological barriers. The internal structure, diameter, zeta potential and rheological properties of selected nanocarriers will be assessed. Subsequently, we will study whether and how formulation composition affects skin permeability, P-glycoprotein-mediated transport and skin penetration and distribution of the drugs. Formulations promoting co-localization of specific combinations of drugs will be selected for evaluation of cytotoxic effects in tumor cells in culture, skin equivalents of cancer and animal models of breast cancer. (AU)
Articles published in Agência FAPESP Newsletter about the research grant:
JUNQUEIRA GARCIA, MARIA TERESA;
GONCALVES, THALITA PEDRALINO;
MARTINS, ERICKA SAO FELIX;
MARTINS, TEREZA SILVA;
DE ABREU FANTINI, MARCIA CARVALHO;
REGAZI MINARINI, PAULO ROBERTO;
FERNANDEZ, SANDRA COSTA;
SALATA, GIOVANNA CASSONE;
LOPES, LUCIANA BIAGINI.
Improvement of cutaneous delivery of methylene blue by liquid crystals.
International Journal of Pharmaceutics,
Web of Science Citations: 5.