Dendrimer space concept for innovative nanomedicine: A futuristic vision for medicinal chemistry

Over the last decade, various nanomaterial systems have been developed as important and powerful strategies to deliver conventional drugs, recombinant proteins, vaccines, aptamers, siRNA, nucleotides and genes. In particular, alongside polymeric, solid-lipid, magnetic and metal based nanoparticles, polymeric micelles and linear polymers, dendrimer nanostructures represent useful nano-carriers in medicine. Today's challenge to find safe and innovative drugs remains as critical as ever.In this review, for the first time, we define the term dendrimer space concept as an approach that affords a new paradigm of thought for medicinal chemists and opens new and promising avenues toward the identification of original dendrimer-based drugs. Thus, the dendrimer space defines a new 'druggable' cluster that is included within the vast volume of chemical space. The dendrimer space concept took its inspiration from both the concepts of 'druglikeness' and 'druggability', which are fully and practically integrated into the drug discovery process, and from different methods of exploration and navigation, such as the 'chemography' approach, in chemical space. It was further influenced by the large number of biomedical applications using dendrimers that were developed from only a handful existing in the early 1990s.To define the boundaries of the dendrimer space, this review first focuses on the recent progress in the exploration of specific sub-chemical spaces (clusters within the continuum of chemical space). Chemical space is defined as the entire collection of all meaningful chemical compounds, and its full examination is insuperable. The compounds included in these different clusters can be mapped onto the coordinates of a multidimensional descriptor space, with such variables as physicochemical properties or topological characteristics, and are based on the concepts of 'druglikeness' (drug-like space) and 'leadlikeness'. In addition, the discrete areas occupied by specific biologically active compounds define the boundaries of the 'target class' clusters, which can overlap the drug-like space. Second, this review gives an overview of the nanopharmaceutical properties of dendrimers, both as biologically active derivatives per se and as drug delivery systems. Finally, several perspectives using dendrimers as new delivery platforms based on the concept of dendrimer space are presented.