Paclitaxel-Triazine Dendrimer Constructs: Efficacy, Toxicity, and Characterization
This chapter reviews work from our laboratory over the last 10 years as it pertains to efforts focused on the exploration of triazine dendrimers as vehicles for drug delivery. The discussion is restricted to our efforts in paclitaxel-laden constructs, an area that we have had the most success and have made the greatest investment in time and energy. Areas of emphasis include the evolution of synthetic strategies, characterization, biodistribution, biocompatibility, safety and toxicity, efficacy, and therapeutic advantage. Throughout, limitations and challenges to these efforts are delineated. This chapter is not intended to exhaustively recapitulate the published work. Interested readers are referred to the original research publications and the supporting information provided with each. Instead, the intent is to provide insight into the evolution of the design and to realize this opportunity to share intuitions currently guiding these efforts which, accordingly, are less (or as yet un-) substantiated with experiment.
KeywordsToxicity Sarcoma Paclitaxel Disulfide Anhydride
The authors thank Dr. Sonke Svenson for the opportunity to convey the contents of our presentation at the National ACS Meeting in Boston (2010) in this forum. In addition to the long-standing efforts of coworkers identified in the relevant citations, the authors wish to thank Dr. Xiankai Sun and Su-Tang Lo of the University of Texas Southwestern Medical Center for ongoing collaboration in this area. Additionally, individuals of the Nanotechnology Characterization Laboratory who contributed to the collection of data on these dendrimers include Stephan Stern, Jeffrey D. Clogston, Jiwen Zheng, Pavan P. Adiseshaiah, Marina Dobrovolskaia, as led by Anil Patri. This work is supported with funds from Texas Christian University. The work is impacted by partnerships with others in related areas, including Drs. Thomas Kissel and Olivia Merkel in Marburg, Dr. Sunil Shaunak in London, Drs. Pete Choyke and Hisataka Kobayashi in Bethesda, and Giovanni Pavan at SUPSI.
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