Bhunia Sukanya, Kolishetti Nagesh, Vashist Arti, Yndart Arias Adriana, Brooks Deborah, Nair Madhavan
Department of Immunology and Nano-Medicine, Herbert Wertheim, College of Medicine, Florida International University, Miami, FL 33199, USA.
Institute of Neuroimmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA.
Pharmaceutics. 2023 Nov 23;15(12):2658. doi: 10.3390/pharmaceutics15122658.
Brain cancers and neurodegenerative diseases are on the rise, treatments for central nervous system (CNS) diseases remain limited. Despite the significant advancement in drug development technology with emerging biopharmaceuticals like gene therapy or recombinant protein, the clinical translational rate of such biopharmaceuticals to treat CNS disease is extremely poor. The blood-brain barrier (BBB), which separates the brain from blood and protects the CNS microenvironment to maintain essential neuronal functions, poses the greatest challenge for CNS drug delivery. Many strategies have been developed over the years which include local disruption of BBB via physical and chemical methods, and drug transport across BBB via transcytosis by targeting some endogenous proteins expressed on brain-capillary. Drug delivery to brain is an ever-evolving topic, although there were multiple review articles in literature, an update is warranted due to continued growth and new innovations of research on this topic. Thus, this review is an attempt to highlight the recent strategies employed to overcome challenges of CNS drug delivery while emphasizing the necessity of investing more efforts in CNS drug delivery technologies parallel to drug development.
脑癌和神经退行性疾病的发病率正在上升，而中枢神经系统（CNS）疾病的治疗方法仍然有限。尽管随着基因治疗或重组蛋白等新兴生物制药的出现，药物开发技术取得了重大进展，但此类生物制药用于治疗CNS疾病的临床转化率极低。血脑屏障（BBB）将大脑与血液分隔开来，保护CNS微环境以维持基本的神经元功能，它对CNS药物递送构成了最大挑战。多年来已经开发了许多策略，包括通过物理和化学方法局部破坏BBB，以及通过靶向脑毛细血管上表达的一些内源性蛋白经转胞吞作用使药物穿过BBB。向大脑给药是一个不断发展的主题，尽管文献中有多篇综述文章，但由于该主题研究的持续增长和新创新，仍有必要进行更新。因此，本综述旨在突出近期为克服CNS药物递送挑战而采用的策略，同时强调在药物开发的同时，有必要在CNS药物递送技术上投入更多努力。
