期刊
PHARMACEUTICS
卷 14, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics14051088
关键词
antibody; affinity; cyclodextrin; protein therapeutics; sustained drug delivery
资金
- NIH [R01 (R01GM121477)]
This paper presents a novel approach to conjugate proteins with polymers and utilize cyclodextrin delivery platforms for sustained release up to 65 days, without significantly compromising protein structure and function, providing important clinical applications in local antibody-based treatments for immune diseases, cancers, and diabetes.
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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