Hyaluronic acid nanoemulsions improve piplartine cytotoxicity in 2D and 3D breast cancer models and reduce tumor development after intraductal administration

Author(s)

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.

• Document type: Journal article
• Source: International Journal of Biological Macromolecules; v. 219, p. 12-pg., 2022-08-05.

Abstract

Nanoemulsions modified with chitosan (NE-Q) or hyaluronic acid (NE-HA), developed for intraductal adminis-tration of piplartine (piperlongumine) and local breast cancer treatment, were evaluated for cytotoxic effects in vitro in 2D and 3D breast cancer models and in vivo in a chemically induced carcinogenesis model. Droplet size was lower than 100 nm, and zeta potential varied from +17.9 to-25.5 mV for NE-Q and NE-HA, respectively. Piplartine nanoencapsulation reduced its IC50 up to 3.6-fold in T-47D and MCF-7 monolayers without differences between NE-Q and NE-HA, and up to 6.6-fold in cancer spheroids. Cytotoxicity improvement may result from a more efficient NE-mediated delivery, as suggested by stronger fluorescent staining of cells and spheroids. In 1-methyl-1-nitrosourea-induced breast cancer models, intraductal administration of piplartine-loaded NE-HA inhibited breast tumor development and histological alterations. These results support the potential applicability of piplartine-loaded NE-HA for intraductal treatment of breast cancer. (AU)

• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/17679-0 - Thermosensitive polymeric nanoparticles for drug co-encapsulation and intraductal delivery into the mammary tissue
• Grantee: Vanessa Franco Carvalho Dartora
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 18/03418-0 - Hypothermia in Sepsis: causes and consequences
• Grantee: Alexandre Alarcon Steiner
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/01208-8 - Bioadhesive nanostructured systems for intraductal administration and localized treatment of Breast Cancer
• Grantee: Julia Sapienza Passos
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 17/04174-4 - Development and evaluation of cationic bioadhesive nanocarriers as a platform to localize piplartine in the breast for tumor treatment
• Grantee: Vanessa Franco Carvalho Dartora
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/17177-6 - Integrative approach on the sustainable prospection of marine natural products: from diversity to anticancer compounds
• Grantee: Leticia Veras Costa Lotufo
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants