In-vitro and In-vivo Anticancer Activity of Pegylated Methotrexate Loaded Silver Nanoparticles

Abstract

Introduction: Chemotherapeutics is the first line of treatment being used worldwide by millions of people to combat cancer. Due to their specificity, insolubility, large molecular size and most importantly their adverse side effects the chemotherapeutic drugs are conjugated with silver nanoparticles. Methotrexate is one of the most widely used drugs for the treatment of many forms of cancer, but methotrexate (MTX) has poor tumor retention ability due to its high water solubility, which likely contributes to its slow or poor therapeutic response in patients. In this study, MTX was bound to silver nanoparticles by chemical reduction method and then capped with PEG to make it biocompatible. The invitro anti-tumor activity and biocompatability of the conjugated nanoparticles (AgMTX) was checked after pegylation . The in-vivo anticancer activity of the nanoparticles was determined by developing a two-stage tumor model in Balb/c mice by chemical carcinogenesis. Results: The characterization of Ag-MTX nanoparticles was done through XRD, zeta potential and particle size evaluation, and drug release efficiency. PEG-AgMTX showed significantly low hemolytic behavior in comparison to AgMTX and MTX. The IC50 value for anticancer activity of PEG-Ag-MTX nanoparticles was less than that of the methotrexate alone showing them more effficient than the original drug. The results of in-vivo studies indicate that the mice treated with PEG-AgMTX showed relatively highest reduction in their tumor volumes, and survival rates. Conclusion: Tailoring of PEG-AgMTX would make them more targets specific with minimal exposure to normal cells with enhanced activity so as small amount of drug causes more toxicity in cancerous cells. It is therefore worthy to investigate in-vivo antitumor activity as well the biodistribution of these nanoparticles.