Lee Seung Ho, Hofstede Roemer Pott, Noriega de la Colina Adrián, Gunton John H, Bernstock Joshua D, Traverso Giovanni
The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Adv Drug Deliv Rev. 2025 Jun;221:115574. doi: 10.1016/j.addr.2025.115574. Epub 2025 Apr 3.
Implantable systems for neurological chronotherapy are poised to revolutionize the treatment of central nervous system diseases and disorders. These devices enable precise, time-controlled drug delivery aligned with the body's circadian rhythms, optimizing therapeutic outcomes. By bypassing the blood-brain barrier, they achieve high local drug concentrations while minimizing systemic side effects, offering significant advantages for conditions where traditional therapies often fall short. Platforms like SynchroMed II and CraniUS showcase this innovation, providing programmable delivery for conditions such as epilepsy and glioblastoma, with customizable profiles ranging from continuous infusion to timed bolus administration. Preclinical and clinical studies underscore the efficacy of aligning drug delivery with circadian rhythms, enhancing outcomes in chrono-chemotherapy and anti-epileptic treatments. Despite their promise, challenges remain, including the invasiveness of implantation within the brain, device longevity, synchronization complexities, and cost(s). Accordingly, this review explores the current state of implantable neurological systems that may be leveraged for chronotherapy, their applications, limitations, and potential to transform neurological disease/disorder management.
用于神经慢性治疗的可植入系统有望彻底改变中枢神经系统疾病和病症的治疗方式。这些装置能够实现与人体昼夜节律同步的精确、定时药物递送，从而优化治疗效果。通过绕过血脑屏障，它们可实现高局部药物浓度，同时将全身副作用降至最低，为传统疗法往往效果不佳的病症带来显著优势。像SynchroMed II和CraniUS这样的平台展示了这一创新，为癫痫和胶质母细胞瘤等病症提供可编程递送，其可定制模式从持续输注到定时推注给药不等。临床前和临床研究强调了使药物递送与昼夜节律同步的有效性，在时辰化疗和抗癫痫治疗中提高了疗效。尽管它们前景广阔，但挑战依然存在，包括脑内植入的侵入性、装置寿命、同步复杂性以及成本等问题。因此，本综述探讨了可用于慢性治疗的可植入神经学系统的当前状态、它们的应用、局限性以及改变神经疾病/病症管理的潜力。
