The Role of Branch Cell Symmetry and Other Critical Nanoscale Design Parameters in the Determination of Dendrimer...

This article reviews progress over the past three decades related to the role of dendrimer-based, branch cell symmetry in the development of advanced drug delivery systems, aqueous based compatibilizers/solubilizers/excipients and nano-metal cluster catalysts. Historically, it begins with early unreported work by the Tomalia Group (i.e., The Dow Chemical Co.) revealing that all known dendrimer family types may be divided into two major symmetry categories; namely: Category I: symmetrical branch cell dendrimers (e.g., Tomalia, Vögtle, Newkome-type dendrimers) possessing interior hollowness/porosity and Category II: asymmetrical branch cell dendrimers (e.g., Denkewalter-type) possessing no interior void space. These two branch cell symmetry features were shown to be pivotal in directing internal packing modes; thereby, differentiating key dendrimer properties such as densities, refractive indices and interior porosities. Furthermore, this discovery provided an explanation for unimolecular micelle encapsulation (UME) behavior observed exclusively for Category I, but not for Category II. This account surveys early experiments confirming the inextricable influence of dendrimer branch cell symmetry on interior packing properties, first examples of Category (I) based UME behavior, nuclear magnetic resonance (NMR) protocols for systematic encapsulation characterization, application of these principles to the solubilization of active approved drugs, engineering dendrimer critical nanoscale design parameters (CNDPs) for optimized properties and concluding with high optimism for the anticipated role of dendrimer-based solubilization principles in emerging new life science, drug delivery and nanomedical applications.