Dogan Alan B, Dabkowski Katherine E, von Recum Horst A
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
Pharmaceutics. 2022 May 19;14(5):1088. doi: 10.3390/pharmaceutics14051088.
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.
在过去几十年中，肽和蛋白质疗法在临床治疗方面取得了巨大进展，但它们在有效递送至患者体内的能力方面在很大程度上受到了阻碍。虽然大剂量肠胃外注射已成为标准临床实践，但对于需要持续局部释放治疗药物的疾病来说，这种方式并不够。基于环糊精的聚合物（pCD）已被用作一个平台，通过利用pCD与有效载荷之间的疏水驱动热力学相互作用来延长小分子疏水性药物的局部递送，从而延长其释放时间，这在体外和体内均取得了成功。在此，我们提出了一种新型的蛋白质-聚合物缀合物的合成方法，该缀合物用“高亲和力”金刚烷封端。以牛血清白蛋白作为模型蛋白，并以抗白细胞介素10单克隆抗体作为功能示例，我们概述了新型蛋白质-聚合物缀合物的合成方法，当与环糊精递送平台结合使用时，该缀合物能够在很大程度上不牺牲蛋白质结构/功能的情况下保持长达65天的持续释放，这在基于抗体的免疫疾病、癌症和糖尿病局部治疗中具有重要的临床应用价值。
