Studies on systemic delivery of insoluble cancer drugs with low-molecular weight methylcellulose

Abstract

Many hydrophobic cancer drugs such as docetaxel (DTX) and etoposide (ETP) have been widely used as cancer treatment agents, but low aqueous solubility is need to be improved for intravenous-injection. So many marketed drugs use surfactants such as polysorbate 80 or ethanol for solubilizing and systemic delivery of hydrophobic drugs intravenously. However, surfactants used to dissolve hydrophobic drugs have been found to cause severe neurotoxicity. In this study, we report the development of bio-eliminable low-molecular weight methylcellulose-based surfactant-free injectable formulation for the delivery of docetaxel and etoposide. Crude methylcellulose was hydrolyzed by cellulase and dialyzed to obtain low-molecular weight methylcellulose. We solubilized hydrophobic drugs using this low-molecular weight methylcellulose by thin-film hydration method. Docetaxel and etoposide were successfully loaded in nanoparticle with about 150nm sizes, with 60~70% drug loading efficiency and slowly sustained release profile. The in vivo anti-cancer effects of intravenously-injected nanoparticle systems in B16F10 melanoma xenograft mice were evaluated and demonstrated a significantly enhanced therapeutic effect with the DTX-loaded LMwMC nanoparticle (DTX-LMwMC) compared to a commercially available docetaxel, Taxotere®. Surfactant-free solubilization of insoluble drugs could be a promising effective and low toxic insoluble drug delivery system for tumor therapy.