Methotrexate (MTX) Anticancer Conjugates with Biotin Using Pamam Dendrimers

Abstract

Methotrexate (MTX) encapsulated in biotinelated dendrimer microparticles (MTX-BD) can be a useful tool for intra-tumor administration showing several benefits in minimizing systemic toxicities of MTX and improve its efficiency in vivo. To develop a biotinelated targeted drug delivery system, we employed dendrimer as a carrier. Biotin molecules were then conjugated on the surface of MTX-BD. The anticancer efficacy of biotin targeted MTX-BD was evaluated in mice bearing 4T1 breast carcinoma. A single dose of biotin targeted MTX-BD showed stronger in vivo antitumor activity than non-targeted MTX-BD and free MTX. By some days after treatment, average tumor volume in the biotin targeted MTX-BD treated group decreased to 17.6% of the initial tumor volume when the number of attached biotin molecules on MTX-BD was the highest. Mice treated with biotin targeted MTX-BD showed slight body weight loss (8%) 21 days after treatment, whereas non-targeted MTX-BD treatment at the same dose caused a body weight loss of 27.05% ± 3.1%.