Combinatorial Assessment of Doxorubicin with Chlorogenic acid by in silico studies and development of its polymeric-nanoparticle against breast cancer

The most common kind of cancer in women is breast cancer, which is treatable in 70 to 80 percent of individuals with early-stage, non-metastatic pathology. With currently available treatments, advanced breast cancer with distant organ metastases is regarded as incurable. The human BRCA mutations are some of the biological characteristics that make breast cancer a diverse disease along with different disruption in MAP Kinase pathway. Different treatment plans are used for various molecular subtypes. Breast cancer treatment is interdisciplinary and comprises both systemic therapy and locoregional therapy (surgery and radiation therapy). In the paper, binding affinities of Ras, Raf, and Erk is checked against Doxorubicin (Synthetic drug for Breast cancer) and Chlorogenic acid (phytocompound). The synergistic effect of Doxorubicin and Chlorogenic acid is checked against the mentioned targets. Further, polymer-based nanoparticles are fabricated by ionic-gelation method with therapeutic compounds, TPP and chitosan, followed by characterization and Release Kinetics. In silico docking results demonstrated the better binding of the synergistic complex rather than doxorubicin and chlorogenic acid for most of the target molecules. Further, the polymer-based nanoparticles were fabricated and encapsulation efficiency was calculated. The optimized formulation is selected and characterized, indicating 78.34 nm size and (-) 23.4 mV of zeta potential surface charge. To further understand the release pattern of the complex, the Franz diffusion cell was used, demonstrating Hixson Crowell's release pattern. As a result, these findings point to a successful formulation of Dox-CGA-NPs and its potential to treat Breast cancer. This nanoformulation can be used going forward on acceptable in vivo models to support its pharmacological efficacy.