Chapter 9 - Safety and toxicity issues of dendrimers

Abstract

Dendrimers are novel three-dimensional, globular, hyperbranched polymeric nanoparticles synthesized and applied in the medical field since the 1980s. The main distinguishing properties of dendrimers include their nanometric size, monodispersity, void space, and suitability in modification of surface functional groups for therapeutic and biomedical applications. The hydrophobic void space in dendrimers helps to encapsulate hydrophobic therapeutic agents, and it results into enhanced solubility and bioavailability of these poorly water-soluble drugs. Thus, application of dendrimers has been extended to deliver a variety of poorly water-soluble therapeutics, viz. anticancer drugs, antiviral agents, and antimicrobials to obtain enhanced solubility and bioavailability of these drugs. The terminal cationic functional groups of dendrimers are responsible for the latter's toxicity due to their interaction with cell membranes, which leads to disruption of cells. These cationic groups are responsible for toxicity of dendrimers, such as hemolysis, hemolytic toxicity, and cytotoxicity in biological systems, which restricts its use in biological systems. The synthesis of biodegradable dendrimers and surface engineering of cationic dendrimers with neutral, anionic, or biodegradable functional groups are the two options to minimize the associated toxicities of dendrimers. Therefore, the dendrimers synthesized with biodegradable core, branching unit, and surface groups such as polyether, polyesters, and polyether amine result in no or minimal toxic manifestation. Furthermore, the surface engineered dendrimers for modification of their branching units and surface functional groups could be used in conjugation with PEG, carbohydrate, peptides, Tuftsin, folic acids, etc., which contributes to targeted or site-specific delivery of therapeutics. Thus, through this chapter, we emphasize the characteristic of dendrimers responsible for their toxicity, and possible ways to overcome the toxic effects on biological systems.