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The evolution of polymer conjugation and drug targeting for the delivery of proteins and bioactive molecules

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Abstract Polymer conjugation can be considered one of the leading approaches within the vast field of nanotechnology‐based drug delivery systems. In fact, such technology can be exploited for delivering an active molecule, such as a small drug, a protein, or genetic material, or it can be applied to other drug delivery systems as a strategy to improve their in vivo behavior or pharmacokinetic activities such as prolonging the half‐life of a drug, conferring stealth properties, providing external stimuli responsiveness, and so on. If on the one hand, polymer conjugation with biotech drug is considered the linchpin of the protein delivery field boasting several products in clinical use, on the other, despite dedicated research, conjugation with low molecular weight drugs has not yet achieved the milestone of the first clinical approval. Some of the primary reasons for this debacle are the difficulties connected to achieving selective targeting to diseased tissue, organs, or cells, which is the main goal not only of polymer conjugation but of all delivery systems of small drugs. In light of the need to achieve better drug targeting, researchers are striving to identify more sophisticated, biocompatible delivery approaches and to open new horizons for drug targeting methodologies leading to successful clinical applications. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine
Schematic representation of the pros and cons of low molecular weight (LMW) and biotech drugs, as well as the potential advantages achievable by polymer conjugation
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Examples of sites of PEGylation by different methods (Reprinted with permission from Pasut and Veronese (2012). Copyright 2019 Elsevier Inc.)
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Timeline of the principal antibody‐drug conjugate (ADC) milestones (Reprinted with permission from Maso et al. (2019). Copyright 2019 Elsevier Inc.)
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Potential approaches to improve and better exploit enhanced permeability and retention effect for tumor targeting. ACE‐II, angiotensin‐II converting enzyme; FGF, fibroblast growth factor; PDGF, platelet‐derived growth factor; TGF‐β, transforming growth factor beta; VEGF, vascular endothelial growth factor
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Timeline of the most important polymer‐drug conjugate developments of LMW and biotech‐drugs (Reprinted with permission from Maso, Grigoletto, Vicent, and Pasut (2019). Copyright 2019 Elsevier Inc.)
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Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Therapeutic Approaches and Drug Discovery > Emerging Technologies

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