Simple Synthesis of Cladribine-Based Anticancer Polymer Prodrug Nanoparticles with Tunable Drug Delivery Properties

Abstract

Polymer prodrugs based on cladribine (CdA) as an anticancer drug have been prepared by growing short, well-defined polyisoprene (PI) chains (with number-average molar mass = 1420–4980 g mol–1 and dispersity = 1.09–1.20) from CdA-bearing alkoxyamine by nitroxide-mediated polymerization. Nanoparticles were formed by nanoprecipitation into water of the resulting CdA-PI conjugates and exhibited long-term colloidal stability in different media, tunable colloidal characteristics, drug release profiles, and anticancer activities in vitro, simply by modulating the drug/polymer linker, the polymer chain length and the formulation parameters. No obvious in vivo toxicity to mice was observed following repeated intravenous injections.