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Review
. 2019 Dec 21;13(1):65.
doi: 10.3390/ma13010065.

Dendrimers as Pharmaceutical Excipients: Synthesis, Properties, Toxicity and Biomedical Applications

Ana Santos  1 , Francisco Veiga  1   2 , Ana Figueiras  1   2
Affiliations
Review

Dendrimers as Pharmaceutical Excipients: Synthesis, Properties, Toxicity and Biomedical Applications

Ana Santos et al. Materials (Basel). .

Abstract

The European Medicines Agency (EMA) and the Current Good Manufacturing Practices (cGMP) in the United States of America, define excipient as the constituents of the pharmaceutical form other than the active ingredient, i.e., any component that is intended to furnish pharmacological activity. Although dendrimers do not have a pharmacopoeia monograph and, therefore, cannot be recognized as a pharmaceutical excipient, these nanostructures have received enormous attention from researchers. Due to their unique properties, like the nanoscale uniform size, a high degree of branching, polyvalency, aqueous solubility, internal cavities, and biocompatibility, dendrimers are ideal as active excipients, enhancing the solubility of poorly water-soluble drugs. The fact that the dendrimer's properties are controllable during their synthesis render them promising agents for drug-delivery applications in several pharmaceutical formulations. Additionally, dendrimers can be used for reducing the drug toxicity and for the enhancement of the drug efficacy. This review aims to discuss the properties that turn dendrimers into pharmaceutical excipients and their potential applications in the pharmaceutical and biomedical fields.

Keywords: biodistribution; dendrimers; drug-delivery systems; pharmaceutical excipient; physicochemical properties; synthesis; toxicity.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Basic structure of a dendrimer.
Figure 2
Figure 2
Schematic representation of the increasing generations of the dendrimer: from first (G0) to third generation (G3).
Figure 3
Figure 3
Dendrimers’ classifications according to their roles in the formulation. The constitution of the dendrimer may confer different activities, namely, anti-inflammatory activity, antiviral activity and antimicrobial activity [13,15]. As a pharmaceutical excipient, dendrimers may enhance distinct properties of the formulation according to the phase of drug product development [27].
Figure 4
Figure 4
Synthesis of dendrimers by the divergent growth method.
Figure 5
Figure 5
Synthesis of dendrimers by the convergent growth method.
Figure 6
Figure 6
Synthesis of dendrimers by the double exponential growth technique.
Figure 7
Figure 7
Synthesis of dendrimers by the double-stage convergent method or the hypercore approach.
Figure 8
Figure 8
Synthesis of dendrimers by the hypermonomer method, or the branched monomer approach.
Figure 9
Figure 9
Comparison of the (a) classical interaction of the free drug with the cell receptor with the (b) enhanced dendrimer interaction.
Figure 10
Figure 10
Schematic representation of the three ways of incorporation of the drug in the dendrimer: (a) covalent binding, (b) electrostatic interactions, and (c) encapsulation.
Figure 11
Figure 11
Cationic dendrimers interact with the negative charges of the lipid bilayer through electrostatic interactions, leading to the formation of nanopores.
Figure 12
Figure 12
Various strategies to decrease the toxicity related to dendrimers.
Figure 13
Figure 13
Several applications of dendrimers in drug delivery.
See this image and copyright information in PMC

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