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Leveraging Affinity Interactions to Prolong Drug Delivery of Protein Therapeutics

While peptide and protein therapeutics have made tremendous advances in clinical treatments over the past few decades, they have been largely hindered by their ability to be effectively delivered to patients. While bolus parenteral injections have become standard clinical practice, they are insuffic...

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Autores principales: Dogan, Alan B., Dabkowski, Katherine E., von Recum, Horst A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144912/
https://www.ncbi.nlm.nih.gov/pubmed/35631672
http://dx.doi.org/10.3390/pharmaceutics14051088
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author Dogan, Alan B.
Dabkowski, Katherine E.
von Recum, Horst A.
author_facet Dogan, Alan B.
Dabkowski, Katherine E.
von Recum, Horst A.
author_sort Dogan, Alan B.
collection PubMed
description While peptide and protein therapeutics have made tremendous advances in clinical treatments over the past few decades, they have been largely hindered by their ability to be effectively delivered to patients. While bolus parenteral injections have become standard clinical practice, they are insufficient to treat diseases that require sustained, local release of therapeutics. Cyclodextrin-based polymers (pCD) have been utilized as a platform to extend the local delivery of small-molecule hydrophobic drugs by leveraging hydrophobic-driven thermodynamic interactions between pCD and payload to extend its release, which has seen success both in vitro and in vivo. Herein, we proposed the novel synthesis of protein–polymer conjugates that are capped with a “high affinity” adamantane. Using bovine serum albumin as a model protein, and anti-interleukin 10 monoclonal antibodies as a functional example, we outline the synthesis of novel protein–polymer conjugates that, when coupled with cyclodextrin delivery platforms, can maintain a sustained release of up to 65 days without largely sacrificing protein structure/function which has significant clinical applications in local antibody-based treatments for immune diseases, cancers, and diabetes.
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spelling pubmed-91449122022-05-29 Leveraging Affinity Interactions to Prolong Drug Delivery of Protein Therapeutics Dogan, Alan B. Dabkowski, Katherine E. von Recum, Horst A. Pharmaceutics Article While peptide and protein therapeutics have made tremendous advances in clinical treatments over the past few decades, they have been largely hindered by their ability to be effectively delivered to patients. While bolus parenteral injections have become standard clinical practice, they are insufficient to treat diseases that require sustained, local release of therapeutics. Cyclodextrin-based polymers (pCD) have been utilized as a platform to extend the local delivery of small-molecule hydrophobic drugs by leveraging hydrophobic-driven thermodynamic interactions between pCD and payload to extend its release, which has seen success both in vitro and in vivo. Herein, we proposed the novel synthesis of protein–polymer conjugates that are capped with a “high affinity” adamantane. Using bovine serum albumin as a model protein, and anti-interleukin 10 monoclonal antibodies as a functional example, we outline the synthesis of novel protein–polymer conjugates that, when coupled with cyclodextrin delivery platforms, can maintain a sustained release of up to 65 days without largely sacrificing protein structure/function which has significant clinical applications in local antibody-based treatments for immune diseases, cancers, and diabetes. MDPI 2022-05-19 /pmc/articles/PMC9144912/ /pubmed/35631672 http://dx.doi.org/10.3390/pharmaceutics14051088 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dogan, Alan B.
Dabkowski, Katherine E.
von Recum, Horst A.
Leveraging Affinity Interactions to Prolong Drug Delivery of Protein Therapeutics
title Leveraging Affinity Interactions to Prolong Drug Delivery of Protein Therapeutics
title_full Leveraging Affinity Interactions to Prolong Drug Delivery of Protein Therapeutics
title_fullStr Leveraging Affinity Interactions to Prolong Drug Delivery of Protein Therapeutics
title_full_unstemmed Leveraging Affinity Interactions to Prolong Drug Delivery of Protein Therapeutics
title_short Leveraging Affinity Interactions to Prolong Drug Delivery of Protein Therapeutics
title_sort leveraging affinity interactions to prolong drug delivery of protein therapeutics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144912/
https://www.ncbi.nlm.nih.gov/pubmed/35631672
http://dx.doi.org/10.3390/pharmaceutics14051088
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