Citation: Huarong Lai, Fenglin Xu, Mingjie Song, Yun Chen, Yi Jin, Jianping Zhou, Yang Ding, Huaqing Zhang. Engineering therapeutics for glioma: Multiscale drug delivery strategies from in-situ drug depots to advanced systemic approaches[J]. Chinese Chemical Letters, ;2026, 37(8): 111759. doi: 10.1016/j.cclet.2025.111759 shu

Engineering therapeutics for glioma: Multiscale drug delivery strategies from in-situ drug depots to advanced systemic approaches

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210000, China

zhoujianp60@163.com

dydszyzf@163.com

zhanghq0527@163.com

Received Date: 3 June 2025
Revised Date: 25 August 2025
Accepted Date: 27 August 2025
Available Online: 28 August 2025

Figures(1)

As the most common primary intracranial brain tumor, glioma is confronted with critical therapeutic dilemmas characterized by dismal prognosis and restricted treatment modalities. The current standard treatment for glioma includes maximally safe resection combined with radiotherapy and temozolomide (TMZ) chemotherapy. However, the presence of the blood-brain barrier (BBB) significantly impedes drug penetration into the brain, further exacerbating the therapeutic challenges in glioma treatment. Consequently, developing effective strategies to deliver drugs across the BBB remains pivotal for glioma therapy. Hence, this comprehensive review examines innovative drug delivery strategies designed to overcome BBB through two principal approaches: in-situ drug depots and advanced systemic delivery systems. The first section analyzes the fundamental biological and anatomical barriers impeding effective glioma management. Then, we critically evaluate emerging in-situ delivery modalities, including biodegradable wafer implants, intratumoral injectable depots, and convection-enhanced delivery (CED) systems. The last section explores advanced systemic drug delivery systems (DDS) and summarizes cutting-edge strategies using functionalized nanoparticles (NPs), biomimetic delivery vectors, and stimulus-responsive DDS for efficient and safe systemic drug delivery. Challenges and future developments related to the application of drug-delivery strategies for glioma treatment are also discussed. In summary, this review not only maps the current landscape of drug delivery strategies but also illuminates transformative research trajectories that can pave the way for precision medicine in glioma treatment.
- Glioma,
- In-situ delivery,
- Systemic drug delivery,
- Brain delivery strategies,
- Nanomaterial
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