Pandian Sureshbabu Ram Kumar, Vijayakumar Kevin Kumar, Murugesan Sankaranarayanan, Kunjiappan Selvaraj
Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil, 626126, Tamilnadu, India.
Department of Molecular Microbiology, School of Biotechnology, Madurai Kamaraj University, Madurai, Tamilnadu, India.
Heliyon. 2022 Jun 4;8(6):e09575. doi: 10.1016/j.heliyon.2022.e09575. eCollection 2022 Jun.
The function of the brain can be affected by various factors that include infection, tumor, and stroke. The major disorders reported with altered brain function are Alzheimer's disease (AD), Parkinson's disease (PD), dementia, brain cancer, seizures, mental disorders, and other movement disorders. The major barrier in treating CNS disease is the blood-brain barrier (BBB), which protects the brain from toxic molecules, and the cerebrospinal fluid (CSF) barrier, which separates blood from CSF. Brain endothelial cells and perivascular elements provide an integrated cellular barrier, the BBB, which hamper the invasion of molecules from the blood to the brain. Even though many drugs are available to treat neurological disorders, it fails to reach the desired site with the required concentration. In this purview, liposomes can carry required concentrations of molecules intracellular by diverse routes such as carrier-mediated transport and receptor-mediated transcytosis. Surface modification of liposomes enables them to deliver drugs to various brain cells, including neurons, astrocytes, oligodendrocytes, and microglia. The research studies supported the role of liposomes in delivering drugs across BBB and in reducing the pathogenesis of AD and PD. The liposomes were surface-functionalized with various molecules to reach the cells intricated with the AD or PD pathogenesis. The targeted and sustained delivery of drugs by liposomes is disturbed due to the antibody formation, renal clearance, accelerated blood clearance, and complement activation-related pseudoallergy (CARPA). Hence, this review will focus on the characteristics, surface functionalization, drug loading, and biodistribution of liposomes respective to AD and PD. In addition, the alternative strategies to overcome immunogenicity are discussed briefly.
大脑功能会受到多种因素的影响,这些因素包括感染、肿瘤和中风。据报道,大脑功能改变所引发的主要疾病有阿尔茨海默病(AD)、帕金森病(PD)、痴呆症、脑癌、癫痫、精神障碍以及其他运动障碍。治疗中枢神经系统疾病的主要障碍是血脑屏障(BBB),它可保护大脑免受有毒分子的侵害,以及脑脊液(CSF)屏障,它将血液与脑脊液分隔开来。脑内皮细胞和血管周围成分构成了一个完整的细胞屏障,即血脑屏障,它阻碍分子从血液侵入大脑。尽管有许多药物可用于治疗神经疾病,但这些药物无法以所需浓度到达预期部位。在这方面,脂质体可以通过多种途径,如载体介导转运和受体介导的转胞吞作用,将所需浓度的分子携带至细胞内。脂质体的表面修饰使其能够将药物递送至各种脑细胞,包括神经元、星形胶质细胞、少突胶质细胞和小胶质细胞。研究支持了脂质体在跨越血脑屏障递送药物以及降低AD和PD发病机制方面的作用。脂质体通过各种分子进行表面功能化,以到达与AD或PD发病机制相关的细胞。由于抗体形成、肾脏清除、加速血液清除以及补体激活相关的假过敏反应(CARPA),脂质体对药物的靶向和持续递送受到干扰。因此,本综述将重点关注与AD和PD相关的脂质体的特性、表面功能化、药物负载和生物分布。此外,还简要讨论了克服免疫原性的替代策略。