QbD-assisted development of lipidic nanocapsules for antiestrogenic activity of exemestane in breast cancer

Abstract

Some breast cancers are caused by hormonal imbalances, such as estrogen and progesterone. These hormones play a function in directing the growth of cancer cells. The hormone receptors in hormone receptor-positive breast cancer lead breast cells to proliferate out of control. Cancer therapy such as hormonal, targeted, radiation is still unsatisfactory because of these challenges namely multiple drug resistance (MDR), off-targeting, severe adverse effects. A novel aromatase inhibitor exemestane (Exe) exhibits promising therapy in breast cancer. This study aims to develop and optimize Exe-loaded lipid nanocapsules (LNCs) by using DSPC, PF68 and olive oil as lipid, surfactant and oil phase, respectively and to characterize the same. The prepared nanocapsules were investigated via in vitro cell culture and in vivo animal models. The LNCs exhibited cytotoxicity in MCF-7 cell lines and enhanced anti-cancer activity and reduced cardiotoxicity in DMBA-induced animal model when compared to the drug. Additionally, in vivo pharmacokinetics revealed a 4.2-fold increased oral bioavailability when compared with Exe suspension. This study demonstrated that oral administration of Exe-loaded LNCs holds promise for the antiestrogenic activity of exemestane in breast cancer.

Keywords:

• Carcinoma
• Exemestane
• 7,12-dimethylbenz[a]anthracene
• lipid nanocapsules
• Mammary gland

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work acknowledges the DST and Government of India for the award of DST INSPIRE Fellowship, Ref No DST/INSPIRE/Fellowship/2018/IF180412. Department of Science and Technology, Ministry of Science and Technology.