Development and evaluation of cationic bioadhesive nanocarriers as a platform to localize piplartine in the breast for tumor treatment

• Grant number: 17/04174-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2017
• End date: January 31, 2021
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Luciana Biagini Lopes
• Grantee: Vanessa Franco Carvalho Dartora
• 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
• Associated scholarship(s): 18/17679-0 - Thermosensitive polymeric nanoparticles for drug co-encapsulation and intraductal delivery into the mammary tissue, BE.EP.DR

Abstract

Breast cancer, one of the most frequent causes of death among women, accounts for about 25% of new cases annually in Brazil and worldwide. The ductal carcinoma in situ corresponds to approximately 25% of the diagnosed types of breast cancer. Due to the risk to originate invasive cancer, these tumors are usually treated with surgery (conservative and / or radical) followed by radiotherapy and/or oral tamoxifen. However, several groups have questioned the need for this aggressive treatment for low grade lesions, which has prompted the interest and in novel strategies for localized treatment. In this project, we propose the development of bioadhesive nanocarriers for intraductal administration of the drug piplartine as a new strategy for the treatment of ductal carcinoma in situ (DCIS). Piplartine (piperlongumine) is an alkaloid / amide component of Piper species that has significant cytotoxic and antiproliferative activity in several tumor cell lines. Due to the absence of specific formulations for intraductal drug administration the lack of effective therapeutic alternatives capable of locating drugs in the breast tissue avoiding systemic exposure and incidence of side effects, we propose to evaluate cationic, bioadhesive nanocarriers for localization of the active agent piplartine in the breast. The positive charge of the systems will be conferred by surface modification with chitosan or cetylpyridine chloride, while and the bioadhesive potential by hyaluronic acid or chitosan. The selected formulations wii be evaluated for particle size, zeta potential, rheological stability and irritation potential. Subsequently, we will study drug retention in the breast, evaluation of the cytotoxic effects in tumor cell lines in bi and tridimensional culture and animal models of breast cancer.

Scientific publications

(8)

(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)

GIACONE, V, DANIELA; DARTORA, VANESSA F. M. C.; DE MATOS, JENYFFER K. R.; PASSOS, JULIA S.; MIRANDA, DANIEL A. G.; DE OLIVEIRA, ERICA A.; SILVEIRA, EDILBERTO R.; COSTA-LOTUFO, V, LETICIA; MARIA-ENGLER, SILVYA S.; LOPES, LUCIANA B.. Effect of nanoemulsion modification with chitosan and sodium alginate on the topical delivery and efficacy of the cytotoxic agent piplartine in 2D and 3D skin cancer models. International Journal of Biological Macromolecules, v. 165, n. A, p. 1055-1065, DEC 15 2020. (17/07856-9, 15/17177-6, 16/16554-3, 17/04174-4, 20/01208-8, 18/18813-1, 18/13877-1)

SANTOS, ROGERIO A.; RAE, MARIANA; DARTORA, VANESSA F. M. C.; MATOS, JENYFFER K. R.; CAMARINI, ROSANA; LOPES, LUCIANA B.. Bioresponsive nanostructured systems for sustained naltrexone release and treatment of alcohol use disorder: Development and biological evaluation. International Journal of Pharmaceutics, v. 585, JUL 30 2020. (17/04174-4, 18/05038-0, 18/13877-1, 13/16617-7, 18/18813-1, 15/02397-0)

CARVALHO, VANESSA F. M.; SALATA, GIOVANNA C.; DE MATOS, JENYFFER K. R.; COSTA-FERNANDEZ, SANDRA; CHORILLI, MARLUS; STEINER, ALEXANDRE A.; DE ARAUJO, GABRIEL L. B.; SILVEIRA, EDILBERTO R.; COSTA-LOTUFO, V, LETICIA; LOPES, LUCIANA B.. Optimization of composition and obtainment parameters of biocompatible nanoemulsions intended for intraductal administration of piplartine (piperlongumine) and mammary tissue targeting. International Journal of Pharmaceutics, v. 567, AUG 15 2019. (17/23213-0, 13/16617-7, 17/04174-4, 18/03418-0, 18/18813-1, 18/13877-1)

PASSOS, JULIA SAPIENZA; DE MARTINO, LUIZA CAPELLO; CARVALHO DARTORA, VANESSA FRANCO; DE ARAUJO, GABRIEL L. B.; ISHIDA, KELLY; LOPES, LUCIANA B.. Development, skin targeting and antifungal efficacy of topical lipid itraconazole. European Journal of Pharmaceutical Sciences, v. 149, JUN 15 2020. (17/04174-4, 14/50928-2, 17/19374-9, 15/07993-0, 18/13877-1, 13/16617-7)

CARVALHO, VANESSA F. M.; GIACONE, DANIELA V.; COSTA-LOTUFO, LETICIA V.; SILVEIRA, EDILBERTO ROCHA; LOPES, LUCIANA B.. Development of a method for quantitative determination of the cytotoxic agent piplartine (piperlongumine) in multiple skin layers. BIOMEDICAL CHROMATOGRAPHY, v. 33, n. 2, FEB 2019. (13/16617-7, 17/07856-9, 17/04174-4)

DARTORA, VANESSA F. C.; SALATA, GIOVANNA C.; PASSOS, JULIA S.; BRANCO, PAOLA C.; SILVEIRA, EDILBERTO; STEINER, ALEXANDRE A.; V. COSTA-LOTUFO, LETICIA; LOPES, LUCIANA B.. Hyaluronic acid nanoemulsions improve piplartine cytotoxicity in 2D and 3D breast cancer models and reduce tumor development after intraductal administration. International Journal of Biological Macromolecules, v. 219, p. 12-pg., 2022-08-05. (14/50928-2, 18/17679-0, 18/03418-0, 20/01208-8, 17/04174-4, 15/17177-6)

PASSOS, JULIA SAPIENZA; DARTORA, VANESSA F. M. C.; SALATA, GIOVANNA CASSONE; MALAGO, ISABELLA DRASZESSKI; LOPES, LUCIANA B.. Contributions of nanotechnology to the intraductal drug delivery for local treatment and prevention of breast cancer. International Journal of Pharmaceutics, v. 635, p. 15-pg., 2023-02-14. (18/13877-1, 17/04174-4, 20/01208-8, 14/50928-2, 19/26048-6)

GIACONE, DANIELA, V; DARTORA, VANESSA F. M. C.; DE MATOS, JENYFFER K. R.; PASSOS, JULIA S.; MIRANDA, DANIEL A. G.; DE OLIVEIRA, ERICA A.; SILVEIRA, EDILBERTO R.; COSTA-LOTUFO, LETICIA, V; MARIA-ENGLER, SILVYA S.; LOPES, LUCIANA B.. Effect of nanoemulsion modification with chitosan and sodium alginate on the topical delivery and efficacy of the cytotoxic agent piplartine in 2D and 3D skin cancer models. International Journal of Biological Macromolecules, v. 165, p. 11-pg., 2020-12-15. (18/13877-1, 18/18813-1, 17/07856-9, 17/04174-4, 20/01208-8, 15/17177-6, 16/16554-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

DARTORA, Vanessa Franco Carvalho. Development and evaluation of bioadhesive cationic nanocarriers as a platform for localizing piplartine in the breast tissue aiming tumor treatment.. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.