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用于阿尔茨海默病治疗的嵌段共聚物:改变生物材料的新视角。

Block copolymers in Alzheimer's disease therapy: A perceptive to revolutionize biomaterials.

机构信息

Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM'S NMIMS, V. L. Mehta Road, Vile Parle (W), Mumbai, India.

Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM'S NMIMS, V. L. Mehta Road, Vile Parle (W), Mumbai, India.

出版信息

J Control Release. 2021 Dec 10;340:271-281. doi: 10.1016/j.jconrel.2021.11.007. Epub 2021 Nov 8.

Abstract

Alzheimer's disease is a fatal illness associated with two persistent problems in treatment i. ineffective drug transportation across the bio-membranes and ii. on-site targeting. Such problems originate from the combinational factors for non-specific targets, physicochemical limitations in the delivery of the active agents and insignificant permeability across blood-brain-barrier. In this context, block copolymers such as PLGA-PEG, PEG-PLA, Poloxamers, PLGA-PEG-PLGA triblock copolymers, etc. present interesting potential in the development of nano-sized carrier systems like polymerosomes, polymeric micelles, etc. for the management and treatment of Alzheimer's disease. Modifications of block copolymers display improvement in solubility and reduction in toxicity due to the process of complexation, functionalization, dose reduction and modification of kinetics for the rate of release. This review article focuses on new insights into different copolymers and their superiority over conventional polymers in Alzheimer's disease for long-term therapy in the body. Association of block copolymers to therapy of Alzheimer's disease overcome the limitations of drug delivery by offering attributes such as smaller molecular size (less than 150 nm), higher solubility owing to hydrophilic interactions between polymeric components and systemic environment, better entrapment efficiency (above 80%) due to large effective surface area and long-term stability for sensitive actives such as peptides, monoclonal antibodies, curcumin, resveratrol, catechins, etc. With such multifunctional features, block copolymers actively permeate the bio-membrane as polymeric nanoparticles, nanomicelles and polymerosomes using different mechanisms such as transcellular- and receptor-mediated transportation to reach target neural network as well as extra-neuronal amyloid-β plaques for anti-Alzheimer's disease activity with neuroprotective action. These polymers emerge as important components for personalized therapy with potential applications in biosensing, drug delivery, theranostics, etc. for qualitative and quantitative predictions in the detection and treatment of Alzheimer's disease.

摘要

阿尔茨海默病是一种致命疾病,与治疗中的两个持续存在的问题有关:i. 生物膜内药物输送效率低;ii. 靶向定位不准。这些问题源于非特异性靶点的组合因素、活性药物输送的物理化学限制以及血脑屏障通透性低。在这种情况下,PLGA-PEG、PEG-PLA、泊洛沙姆、PLGA-PEG-PLGA 三嵌段共聚物等嵌段共聚物在开发聚合物体、聚合物胶束等纳米载体系统方面具有很大的潜力,可用于阿尔茨海默病的管理和治疗。嵌段共聚物的修饰可通过络合、功能化、减少剂量和改变释放速率的动力学来提高其溶解度并降低其毒性。本文综述了不同嵌段共聚物的新见解,以及它们在阿尔茨海默病治疗中的优势,以实现长期的体内治疗。嵌段共聚物与阿尔茨海默病治疗的结合克服了药物输送的局限性,通过提供较小的分子尺寸(小于 150nm)、由于聚合物成分与系统环境之间的亲水相互作用而提高的溶解度、由于大的有效表面积而提高的更好的包封效率(高于 80%)以及对肽、单克隆抗体、姜黄素、白藜芦醇、儿茶素等敏感活性物质的长期稳定性等属性来提供治疗效果。嵌段共聚物具有这些多功能特性,可作为聚合物纳米颗粒、纳米胶束和聚合物体积极动地渗透生物膜,使用跨细胞和受体介导的输送等不同机制,到达目标神经网络以及额外的神经淀粉样β斑块,发挥抗阿尔茨海默病活性和神经保护作用。这些聚合物作为个性化治疗的重要组成部分,具有在生物传感、药物输送、治疗学等方面的潜在应用,可用于阿尔茨海默病的定性和定量预测的检测和治疗。

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