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Proteolysis targeting chimeras (PROTACs) have been extensively explored for targeted proteasomal degradation of disease-related proteins with enormous potential in the treatment of intractable diseases. However, PROTACs are poorly soluble and permeable bulky molecules facing several bioavailability challenges irrespective of the route of administration. Our review lays out crucial challenges in the delivery of target protein degraders and nanoformulation approaches to overcome physicochemical and biological hurdles that can aid in transporting these target-protein degraders to the disease site. We have elaborated on the current formulation approaches and further highlighted the prospective delivery strategies that could be probed for disease-specific targeted delivery of PROTACs. Copyright © 2022 Elsevier Ltd. All rights reserved.


Aishwarya L Saraswat, Richa Vartak, Rehab Hegazy, Akanksha Patel, Ketan Patel. Drug delivery challenges and formulation aspects of proteolysis targeting chimera (PROTACs). Drug discovery today. 2023 Jan;28(1):103387

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PMID: 36184017

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