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

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.

Automated summary

In this study, nanoemulsions modified with chitosan or hyaluronic acid were evaluated for their cytotoxic effects in breast cancer models. The results showed that nanoencapsulation improved the cytotoxicity of piplartine, possibly through more efficient drug delivery. In an in vivo model, piplartine-loaded nanoemulsion administered through intraductal delivery successfully inhibited breast tumor development.