Design and evaluation of cabazitaxel loaded NLCs against breast cancer cell lines

Abstract

Cabazitaxel (CBZ) is a taxane derivative and an anti-microtubule agent effective against numerous cancers including drug-resistant cancers. In this study, CBZ loaded nanostructured lipid carriers (NLCs) were prepared by using Design-Expert (DoE) and optimized for various formulation parameters (ratio of lipids and surfactant concentration, homogenization speed and time). The optimized CBZ loaded NLCs formulation was characterized and evaluated through multiple physicochemical characterization techniques like FTIR, DSC, PXRD, SEM and in-vitro drug release. FTIR and DSC results suggested that NLCs entrapped drug inside and had no chemical bonding between drug and NLCs. SEM analysis confirmed homogeneous, spherical, and uniformly distributed NLCs. In-vitro cell culture studies suggested that CBZ loaded NLCs produced ∼ 6- and 2.5-times higher cytotoxicity against MDA-MB-468 and MCF-7 cell lines, respectively compared to pure drug. Cellular uptake of NLC was ∼2.5 and 2.1-fold higher than CBZ alone in MDA-MB-468 and MCF-7 cell lines, respectively. Furthermore, CBZ loaded NLCs produced significantly higher apoptosis and inhibited the mobility of MDA-MB-468 and MCF-7 cells. The results from this study demonstrate the utility of CBZ loaded NLCs as an effective treatment against breast cancer and NLCs as effective drug carriers to deliver the highly lipophilic drug such as CBZ.

Keywords: Apoptosis; Breast cancer; Cabazitaxel; Design of experiment; Nanostructured lipid carriers.