Development, characterization and evaluation of microemulsions for paclitaxel and ceramide C6 topical delivery

• Grant number: 15/23976-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2016
• End date: January 31, 2017
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Luciana Biagini Lopes
• Grantee: Amanda Migotto
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/16617-7 - Nanostructured systems for topical delivery and co-localization of chemopreventive and chemoterapeutic agents in the skin and breast tissue, AP.JP

Abstract

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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NG, WING Y.; MIGOTTO, AMANDA; FERREIRA, THAMYRES SOARES; LOPES, LUCIANA B.. Monoolein-alginate beads as a platform to promote adenosine cutaneous localization and wound healing. International Journal of Biological Macromolecules, v. 102, p. 1104-1111, SEP 2017. (13/16617-7, 15/23976-9)

CARVALHO, VANESSA F. M.; MIGOTTO, AMANDA; GIACONE, DANIELA V.; DE LEMOS, DEBORA P.; ZANONI, THALITA B.; MARIA-ENGLER, SILVYA S.; COSTA-LOTUFO, LETICIA V.; LOPES, LUCIANA B.. Co-encapsulation of paclitaxel and C6 ceramide in tributyrin-containing nanocarriers improve co-localization in the skin and potentiate cytotoxic effects in 2D and 3D models. European Journal of Pharmaceutical Sciences, v. 109, p. 131-143, NOV 15 2017. (16/04913-9, 13/16617-7, 15/23976-9, 14/24400-0)