PROTEIN STABILIZED 4-PB AND EPIRUBICIN LOADED NANOPARTICLES FOR EFFECTIVE ANTICANCER ACTIVITY

Abstract

One of the main reasons for cancer-related fatalities worldwide is lung cancer. It happens when abnormal cells in the lungs develop and create a tumor. The World Health Organization (WHO) estimates that lung cancer causes 1.8 million fatalities each year. It is the second most prevalent malignancy and the main reason for cancer-related fatalities. In the treatment of cancer, drugs based on nanomedicine can offer enhanced medication delivery and prolonged drug release. Bovine Serum Albumin is a protein very commonly used in drug delivery due to its biocompatibility and its ability to self-assemble into nanoparticles. Epirubicin can be encapsulated within BSA nanoparticles (EPI BSA NP), which will improve the drug's solubility and bioavailability, and it helps in the slow and sustained release of the drug. It is expected that this type of encapsulation of chemotherapeutic drugs reduces systemic toxicity and side effects associated with traditional chemotherapy. In the present investigation, we found out that EPI BSA NP is not that effective as compared to free drug and a very high concentration of the NPs is actually required to show significant cytotoxic effect. Moreover, it was not effective against the A549 cell line that had become resistant to Epirubicin Drug. Thus, in the second section of this study we have tried to fabricate a new nanoparticle- where we have encapsulated Sodium phenyl butyrate drug (4PB) along with Epirubicin in BSA NPs. (4PB-EPI BSA NP). Sodium Phenylbutyrate (4-PB) is a histone deacetylase inhibitors (HDACi) .Histone deacetylase inhibitors (HDACi) are a novel class of drugs with potent connexin expression-modulating abilities and strong anticancer efficacy. It has been reported that 4PB has a synergistic effect and when used in combination with anticancer drugs like cisplatin, erlotinib, or gefitinib, it sensitises the resistant non-small-cell lung cancer (NSCLC) cells to the anticancer drug.1 Thus we have tested whether the newly fabricated nanopartihas a synergistic effect and whether it can increase the efficacy of Epirubicin drug when encapsulated with it in BSA NPs. The results from various in vitro experiments suggest that the 4PB EPI BSA NPs have a greater efficacy in killing the lung cancer cells as compared EPI BSA NPs. Since, EPI has a natural red fluorescence the fabricated 4PB EPI NPs can be used for imaging as well along with cancer therapy thus making it a good candidate for nanotheranostic application.