Biocompatible Polymeric Nanoparticles for Effective Codelivery of Tamoxifen with Ganoderic Acid A: Systematic Approach for Improved Breast Cancer Therapeutics

In this research work, tamoxifen (TF) and ganoderic acid A (GA-A)-loaded polymeric nanoparticles (PNP) were developed to treat MDA-MB-231 human breast cancer in the mammary breast tumour model. The developed PNP was evaluated for their in vitro and in vivo efficacy using DMBA-induced rat model. The optimized formulation was found to be with mean particle size distribution of 155.7 nm and PDI of 0.27, while TEM imaging also confirmed size in the range of 120 nm to 180 nm. Further, drug entrapment and drug loading were found to be 92.2% and 13.4%, respectively. In vitro gastrointestinal drug stability analysis showed insignificant variations (p > 0.05) in the values of particle size, PDI and drug entrapment efficiency. In vitro drug release analysis revealed a biphasic pattern with an initial drug release of 60.01% in 6 h, followed by sustained drug release up to 94.2% in 24 h. In vitro cytotoxicity studies indicated significantly reduced cell viability with IC₅₀ reaching a minimum value after 72 h. TF with GA-A loaded PNP exhibited 11.7% tumour incidence and lowest average tumour weight (2.4 ± 1.2 g) in the DMBA-treated group of rats, thus demonstrated highest recovery and reduction in relative tumour volume. In the DMBA-induced rat breast tumor model, TF with GA-A loaded PNP showed maximal normalization of haematological parameters, mitochondrial enzymes and other parameters such as antioxidants and inflammatory cytokines. In a nutshell, the dual drug-loaded PNP outperformed over other formulations, thus signifying a superior anticancer activity in the DMBA induced breast tumor model in rats.