Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.
Department of Radiation Biology & Toxicology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.
Life Sci. 2021 Jun 1;274:119326. doi: 10.1016/j.lfs.2021.119326. Epub 2021 Mar 9.
The blood-brain barrier (BBB) is composed of a layer of endothelial cells that is interspersed with a series of tight junctions and characterized by the absence of fenestrations. The permeability of this barrier is controlled by junctions such as tight junctions and adherent junctions as well as several cells such as astrocytes, pericytes, vascular endothelial cells, neurons, microglia, and efflux transporters with relatively enhanced expression. It plays a major role in maintaining homeostasis in the brain and exerts a protective regulatory control on the influx and efflux of molecules. However, it proves to be a challenge for drug delivery strategies that target brain diseases like Dementia, Parkinson's Disease, Alzheimer's Disease, Brain Cancer or Stroke, Huntington's Disease, Lou Gehrig's Disease, etc. Conventional modes of drug delivery are invasive and have been known to contribute to a "leaky BBB", recent studies have highlighted the efficiency and relative safety of receptor-mediated drug delivery. Several receptors are exhibited on the BBB, and actively participate in nutrient uptake, and recognize specific ligands that modulate the process of endocytosis. The strategy employed in receptor-mediated drug delivery exploits this process of "tricking" the receptors into internalizing ligands that are conjugated to carrier systems like liposomes, nanoparticles, monoclonal antibodies, enzymes etc. These in turn are modified with drug molecules, therefore leading to delivery to desired target cells in brain tissue. This review comprehensively explores each of those receptors that can be modified to serve such purposes as well as the currently employed strategies that have led to increased cellular uptake and transport efficiency.
血脑屏障（BBB）由一层内皮细胞组成，这些细胞之间散布着一系列紧密连接，其特征是没有窗孔。这种屏障的通透性由紧密连接和黏附连接等连接以及星形胶质细胞、周细胞、血管内皮细胞、神经元、小胶质细胞和具有相对增强表达的外排转运体等几种细胞来控制。它在维持大脑内环境稳定方面起着重要作用，并对分子的内流和外流施加保护调节控制。然而，对于针对痴呆症、帕金森病、阿尔茨海默病、脑癌或中风、亨廷顿病、葛雷克氏症等脑部疾病的药物输送策略来说，这是一个挑战。传统的药物输送模式具有侵入性，并且已知会导致“血脑屏障渗漏”，最近的研究强调了受体介导的药物输送的效率和相对安全性。几种受体在 BBB 上表达，并积极参与营养物质的摄取，并识别调节内吞作用过程的特定配体。受体介导的药物输送所采用的策略利用了“欺骗”受体内化与载体系统（如脂质体、纳米颗粒、单克隆抗体、酶等）结合的配体的过程。这些载体系统反过来又被修饰有药物分子，从而导致递送到脑组织中所需的靶细胞。本综述全面探讨了可用于此类目的的每种受体，以及导致细胞内摄取和转运效率提高的当前采用的策略。
