Polymer–drug conjugates as nano-sized multi-targeting systems for the treatment of Alzheimer's disease

Nuruddin Mahadik, Gemma A. Barron, Paul Kong Thoo Lin and Colin J. Thompson
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Abstract

Alzheimer's disease (AD) is a progressive, neurodegenerative condition. There are clear markers for the presence and progression of the disease, including β-amyloid (Aβ) plaques and Tau tangles, with many potential causes debated in the scientific community. Most existing treatments only provide symptomatic solutions. Due to poor aqueous solubility and possibly limited uptake across the blood–brain barrier (BBB), medications targeting the hallmarks of AD are still under study despite enormous efforts. Recently, nanoparticle-based drug delivery systems have demonstrated remarkable promise as precision medicines that may effectively increase bioavailability, permeate the BBB, and improve the targeting ability of a variety of pharmaceuticals. Polymer therapeutics have made tremendous progress in recent years, particularly in cancer treatment. Polymer–drug conjugates (PDCs) typically have a longer half-life, higher stability, and enhanced water solubility. Polymers serve as carriers for the administration of drugs, proteins, targeting moieties, and imaging agents in polymeric and macromolecular prodrugs. Numerous commercially viable PDCs for the treatment of various diseases have already proved their potential. This paper focuses mainly on the rationale for the design, synthesis, and potential use of PDCs as a multi-target treatment for neurodegenerative diseases.

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聚合物-药物共轭物作为治疗阿尔茨海默病的纳米级多靶点系统
阿尔茨海默病(AD)是一种进行性神经退行性疾病。这种疾病的存在和发展有明确的标志物,包括β-淀粉样蛋白(Aβ)斑块和Tau缠结。现有的大多数治疗方法只能对症下药。由于水溶性较差,通过血脑屏障(BBB)的吸收可能有限,尽管付出了巨大努力,但针对注意力缺失症特征的药物仍在研究之中。最近,基于纳米颗粒的给药系统作为一种精准药物已显示出显著的前景,可有效提高生物利用度、渗透 BBB 并改善各种药物的靶向能力。近年来,聚合物疗法取得了巨大进展,尤其是在癌症治疗方面。聚合物-药物共轭物(PDC)通常具有更长的半衰期、更高的稳定性和更强的水溶性。聚合物和大分子原药中的聚合物可作为药物、蛋白质、靶向分子和成像剂的载体。许多用于治疗各种疾病的商业化 PDC 已经证明了它们的潜力。本文主要介绍 PDCs 的设计原理、合成以及作为神经退行性疾病多靶点治疗药物的潜在用途。
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