Dendrimers as Biopharmaceuticals: Synthesis and Properties

Carolina      Villalonga-Barber; Maria      Micha-Screttas; Barry   R.   Steele; Aristidis      Georgopoulos; Costas      Demetzos

Abstract

Two general aspects which need to be considered for the successful application of dendrimers for biomedical purposes are their availability at an acceptable cost and their suitability as regards their pharmacodynamic and pharmacokinetic properties. These two aspects are covered in this review. In the first part, synthetic strategies for the preparation of dendrimers are outlined and emphasis is given to recent work on methodologies whose aim is the development of more efficient routes to dendrimers in terms of the materials used for their synthesis as well as in terms of the procedures required for their purification. These include procedures involving double-stage and double exponential synthesis, orthogonal coupling strategies, self-assembly and solid-phase approaches, as well as particularly useful synthetic protocols such as those used in “click chemistry”. The second part of the review deals with the way in which the size, chemical constitution and physicochemical properties of dendrimers used for drug delivery may affect pharmacodynamic and pharmacokinetic parameters which are important considerations for drug bioavailability. This is illustrated by an overview of examples from recent work involving non-steroidal anti-inflammatory drugs, anticancer drugs and antibacterials.

Keywords: Dendrimer synthesis, double-stage synthesis, double exponential synthesis, orthogonal coupling, lego chemistry, click chemistry, self-assembly, solid-phase synthesis, pharmacodynamics, pharmacokinetics