Pharmaceutical Applications and Safety Review of Dendrimers

This article describes the innovative approaches to overcome the cationic toxicity inherently associated with the dendrimers. A dendrimer is a macromolecule characterized by its highly branched 3D structure that provides a high degree of surface functionality and versatility. The toxicity is attributed to the interaction of surface cationic charge of dendrimers with negatively charged biological membranes in vivo. Dendrimer toxicity in biological system is generally characterized by hemolytic toxicity, cytotoxicity and hematological toxicity. To minimize this toxicity, two strategies have been utilized; first, designing and synthesis of biocompatible dendrimers; and second, masking of peripheral charge of dendrimers by surface engineering. Biocompatible dendrimers can be synthesized by employing biodegradable core and branching units or utilizing intermediates of various metabolic pathways. Dendrimer biocompatibility has been evaluated in vitro and in vivo for efficient presentation of biological performance. Neutral and negatively charged dendrimers do not interact with biological environment and hence are compatible for clinical applications as elucidated by various studies examined in this review. Chemical modification of the surface is an important strategy to overcome the toxicity problems associated with the dendrimers.