Exercise and Metabolism Research Center, College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua, Zhejiang, China.
Department of Biological Sciences, Missouri University of Science and Technology, Rolla, MO 65409-1120, United States.
Curr Pharm Des. 2021;27(6):816-825. doi: 10.2174/1381612826666201019102640.
BACKGROUND/PURPOSE: Type 2 diabetes (T2D) is characterized by hyperglycemia resulting from the body's inability to produce and/or use insulin. Patients with T2D often have hyperinsulinemia, dyslipidemia, inflammation, and oxidative stress, which then lead to hypertension, chronic kidney disease, cardiovascular disease, and increased risk of morbidity and mortality (9th leading cause globally). Insulin and related pharmacological therapies are widely used to manage T2D, despite their limitations. Efficient drug delivery systems (DDS) that control drug kinetics may decrease side effects, allow for efficient targeting, and increase the bioavailability of drugs to achieve maximum therapeutic benefits. Thus, the development of effective DDS is crucial to beat diabetes.
Here, we introduced a highly bioavailable vector, cell-penetrating peptides (CPPs), as a powerful DDS to overcome limitations of free drug administration.
CPPs are short peptides that serve as a potent tool for delivering therapeutic agents across cell membranes. Various cargoes, including proteins, DNA, RNA, liposomes, therapeutic molecules, and nanomaterials, generally retain their bioactivity upon entering cells. The mechanisms of CPPs/cargoes intracellular entry are classified into two parts: endocytic pathways and direct membrane translocation. In this article, we focus on the applications of CPPs/therapeutic agents in the treatment of diabetes. Hypoglycemic drugs with CPPs intervention can enhance therapeutic effectiveness, and CPP-mediated drug delivery can facilitate the actions of insulin. Numerous studies indicate that CPPs can effectively deliver insulin, produce synergistic effects with immunosuppressants for successful pancreatic islet xenotransplantation, prolong pharmacokinetics, and retard diabetic nephropathy.
We suggest that CPPs can be a new generation of drug delivery systems for effective treatment and management of diabetes and diabetes-associated complications.
背景/目的：2 型糖尿病（T2D）的特征是由于身体无法产生和/或使用胰岛素而导致的高血糖。T2D 患者常伴有高胰岛素血症、血脂异常、炎症和氧化应激，进而导致高血压、慢性肾脏病、心血管疾病，并增加发病率和死亡率（全球第九大主要死因）的风险。尽管存在局限性，但胰岛素和相关的药理疗法仍被广泛用于治疗 T2D。控制药物动力学的高效药物递送系统（DDS）可以减少副作用，实现高效靶向，并提高药物的生物利用度，从而实现最大的治疗效果。因此，开发有效的 DDS 对于战胜糖尿病至关重要。
在这里，我们引入了一种高生物利用度的载体，即细胞穿透肽（CPP），作为一种强大的 DDS，以克服游离药物给药的局限性。
CPP 是短肽，可作为将治疗剂递送至细胞膜内的有效工具。各种载物，包括蛋白质、DNA、RNA、脂质体、治疗分子和纳米材料，在进入细胞后通常保持其生物活性。CPP/载物进入细胞的机制分为两部分：内吞途径和直接膜转位。在本文中，我们重点介绍 CPP/治疗剂在糖尿病治疗中的应用。CPP 干预的降血糖药物可以增强治疗效果，而 CPP 介导的药物递送可以促进胰岛素的作用。许多研究表明，CPP 可以有效地递送达胰岛素，与免疫抑制剂产生协同作用，成功实现胰岛异种移植，延长药代动力学，并延缓糖尿病肾病。
我们认为 CPP 可以成为治疗和管理糖尿病及其相关并发症的新一代药物递送系统。
