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  • Review Article
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Evolution of macromolecular complexity in drug delivery systems

Abstract

Designing therapeutics is a process with many challenges. Even if the first hurdle — designing a drug that modulates the action of a particular biological target in vitro — is overcome, selective delivery to that target in vivo presents a major barrier. Side-effects can, in many cases, result from the need to use higher doses without targeted delivery. However, the established use of macromolecules to encapsulate or conjugate drugs can provide improved delivery, and stands to enable better therapeutic outcomes. In this Review, we discuss how drug delivery approaches have evolved alongside our ability to prepare increasingly complex macromolecular architectures. We examine how this increased complexity has overcome the challenges of drug delivery and discuss its potential for fulfilling unmet needs in nanomedicine.

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Figure 1: Analysis of macromolecular structure evolution in drug delivery.
Figure 2: Macromolecular architectures in drug delivery and examples of the methodologies for their synthesis.
Figure 3: Common drug delivery methods: oral, intravenous, transdermal and local administration.
Figure 4: Self-assembled structures from an ABC-type amphiphilic miktoarm polymer.
Figure 5: Synthesis of architecturally complex branched macromolecular structures.
Figure 6: Examples of smart nanoassemblies constructed using a combination of different synthetic methodologies.
Figure 7: Telodendrimers combine important characteristics of hyperbranched and monodisperse dendrons with those of linear polymers.
Figure 8: Polymer backbones are grafted with pendant targeting moieties that contain conjugated antiparallel coiled-coil peptides.
Figure 9: Anti-inflammatory activity of drug-free macromolecules.

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Acknowledgements

The authors thank the Prostate Cancer Foundation, National Cancer Institute (NIH Grant No. 1U54CA151884), and Natural Sciences and Engineering Research Council of Canada (A.K.) for financial support.

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O.C.F. and R.L. declare competing interests in Selecta Biosciences and Tarveda Therapeutics.

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Kakkar, A., Traverso, G., Farokhzad, O. et al. Evolution of macromolecular complexity in drug delivery systems. Nat Rev Chem 1, 0063 (2017). https://doi.org/10.1038/s41570-017-0063

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