Scale up synthesis of ART207, a paclitaxel-based lipophilic prodrug for tumor selective delivery via pseudo-LDL nanoparticles

Abstract

The ultimate goal of an anticancer regime is to eliminate tumor cells without harming healthy cells. However, currently used chemotherapeutic drugs are not selective and hence attack both healthy and tumor cells which results in very serious side effects. Targeted delivery of anticancer drugs to tumors utilizing nanoparticles has been the focus of the scientific community as well as pharmaceutical companies with the hope of selectively delivering the drug to the cancer cell and increasing the efficacy of the drug while reducing systemic toxicity. Arbor Therapeutics has developed a targeted delivery approach based on the synthesis of acid-labile lipophilic prodrugs of approved clinical anticancer drugs and their formulation into pseudo-LDL nanoparticles for selective tumor delivery via over expressed LDL receptors. A paclitaxel-based lipophilic prodrug, ART207, has been synthesized starting from methyl oleate ester. Challenges of the scale-up process and the separation of ART206 stereoisomers will be discussed in detail. ART207 has shown cytotoxicity to several paclitaxel sensitive cell lines including prostate, breast and ovarian.