Exploring the synergistic behavior of paclitaxel and vorinostat upon co-loading in albumin nanoparticles for breast cancer management.

ABSTRACT

Breast cancer is challenging to treat accompanied with poor clinical outcomes. Paclitaxel (PTX) is a first-line chemotherapeutic agent, but possesses limitations due to side effects, high dose, non-specific tissue distribution, and drug resistance. An epigenetic modulator, vorinostat (VOR) is known to enhance PTX efficacy and therefore to resolve the issues of conventional PTX formulations, we designed PTX- and VOR-bound albumin nanoparticles (PTX-VOR-BSA-NPs) using antisolvent precipitation technique where albumin is used as a carrier and a targeting agent. The PTX-VOR-BSA-NPs were of 140 nm size, polydispersity index around 0.18, and about 78% and 68% of entrapment efficiency for PTX and VOR, respectively. A bi-pattern release of both PTX and VOR was observed from PTX-VOR-BSA-NPs with a burst release for 2 h succeeded by sustained release until 24 h. A significantly lower %cell viability was observed in MCF-7 cell lines, while efficient cellular drug uptake was found in MDA-MB-231 cells. Furthermore, a greater apoptotic index was found compared to free PTX and VOR because of the synergistic activity of these drugs. The PTX-VOR-BSA-NPs also showcased superior pharmacokinetic profile and noteworthy reduction in the tumor volume compared to Intaxel in 4T1 cell line-induced breast tumor model. Further, the NPs showed similar levels of toxicity biomarkers as that of control. Overall, the developed PTX-VOR-BSA-NPs were found to have less toxicity and more effectiveness compared to the marketed formulation, thus affirming the generation of a potent as well as and safe product.