Bypassing the blood-brain barrier: a novel drug delivery pathway via the skull bone marrow-dura-glymphatic system

doi:10.3969/j.issn.1006-7795.2026.01.002

Journal of Capital Medical University

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Bypassing the blood-brain barrier: a novel drug delivery pathway via the skull bone marrow-dura-glymphatic system

Zhang Meiyang, Chen Zhuangzhuang, Wang Nanxing, Ji Ruobing, Yang Mo, Wang Yilong^*

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China

Received:2025-11-03 Revised:2025-11-26 Online:2026-02-21 Published:2026-01-20
Supported by:
This study was supported by National Natural Science Foundation of China (82425101), Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0504800, 2023ZD0504801, 2023ZD0504802, 2023ZD0504803, 2023ZD0504804), Beijing Municipal Science & Technology Commission(Z231100004823036）, A Grant from the Chinese Institutes for Medical Research, Beijing(CX25YZ07), Capital's Funds for Health Improvement and Research(2022-2-2045), National Key Research and Development Program of China(2024YFC3044800, 2022YFF1501500, 2022YFF1501501, 2022YFF1501502, 2022YFF1501503, 2022YFF1501504, 2022YFF1501505).

Abstract

Abstract: Under physiological conditions, the blood-brain barrier (BBB) blocks over 95% of various drugs from entering the central nervous system (CNS). How to achieve precise and efficient intracranial drug delivery by overcoming the BBB in a minimally invasive or non-invasive manner has become one of the current challenges in pharmaceutical research and development. This review summaries the feasibility and efficacy of a novel CNS drug delivery pathway that bypasses the BBB through the skull bone marrow-dura-glymphatic system, to provide new perspectives and strategies for drug delivery and treatment in a range of major brain diseases.

Key words: central nervous system drug delivery, intracalvariosseous drug administration, blood-brain barrier, glymphatic system, immunological surveillance, brain-bone marrow axis, skull bone marrow immunity

CLC Number:

R743

Zhang Meiyang, Chen Zhuangzhuang, Wang Nanxing, Ji Ruobing, Yang Mo, Wang Yilong. Bypassing the blood-brain barrier: a novel drug delivery pathway via the skull bone marrow-dura-glymphatic system[J]. Journal of Capital Medical University, doi: 10.3969/j.issn.1006-7795.2026.01.002.

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Bypassing the blood-brain barrier: a novel drug delivery pathway via the skull bone marrow-dura-glymphatic system

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