Dendrimer-Based Nanoparticle Therapies: Can Uniform Multifunctional Therapeutics Be Made with Current Chemical Approaches?

Abstract

The development of multifunctional, dendrimer-based therapeutics has been a major focus of the Michigan Nanotechnology Institute for Medicine and Biological Sciences {(MNIMBS)} over the past 15 years. Based on the success of this platform technology in the laboratory, clinical translational activities were expected to be easily accomplished. Unfortunately, efforts to bring this technology to the clinic have been impeded by several challenges that have centered on the reproducible production of a multifunctional dendrimer, which has proved far more difficult than anticipated. The primary challenges involved the variability and heterogeneity of the starting dendrimer, the development of analytical methods capable of defining the composition and assessing the reproducibility of the intermediate and final products, and the evolution of synthetic strategies that produce reproducible batches of multifunctionalized dendrimers. These issues became magnified during scale-up synthesis of the therapeutics. Importantly, the challenges observed with dendrimers are not exclusive to this material, but are common to most multifunctional nanoparticle-based therapeutics that are being developed. Therefore, this chapter will describe several strategies that have been utilized to address the aforementioned challenges in dendrimer therapeutics with the hope that adapting these strategies to other therapeutic systems will help facilitate and enable clinical application.