Work

A postoperative in situ drug delivery system based on biphasic drug-release and “Three-in-One” Effect of curcumin to inhibit the recurrence of glioma

Year: 2025

Type: article

Abstract: The standard treatment for glioma is surgical resection of the tumor followed by postoperative temozolomide-based radio chemotherapy. However, the survival rate remains poor. This study, aiming to address the challenge of postoperative glioma recurrence, developed a reactive oxygen species-sensitive and thermo-sensitive gel to form biphasic drug-release postoperative in situ drug delivery system (PIDDS). This system simultaneously carried free temozolomide, free curcumin, and drug-loaded PLGA nanoparticles. Through a “rapid release + sustained release” biphasic drug-release mode and the “three-in-one” effect of curcumin, it enhanced the chemo sensitization of temozolomide, inhibited the glioma stem cells, and regulated the postoperative recurrence microenvironment, to achieve synergistic tumor recurrence inhibition. In vitro and in vivo experiments have shown this dual-sensitive gel PIDDS had a cumulative drug-release rate of over 88 % within 30 days, significantly extending the median survival time of rats to 57 days, 3 times higher than that of control group, while reducing systemic toxicity. The study has confirmed the PIDDS worked by disrupting DNA repair, inhibiting JAK-STAT stemness pathway, and reprogramming metabolic microenvironment, thus providing a new strategy for precise postoperative treatment of glioma. This study, aiming to address the challenge of postoperative glioma recurrence, developed a reactive oxygen species-sensitive and thermo-sensitive gel to form biphasic drug-release postoperative in situ drug delivery system, through a “rapid release + sustained release” biphasic drug-release mode and the “three-in-one” effect of curcumin, to achieve synergistic tumor recurrence inhibition. Our study (A Postoperative In in Situ Drug Delivery System Based on Biphasic Drug-Release and “Three-in-One” Effect of Curcumin to Inhibit the Recurrence of Glioma, ID: IJPHARMX-D-25-00212R1) has 3 highlights: • 1. A biphasic drug-release postoperative in situ gel system was developed, integrating rapid release of free TMZ/Cur with sustained nanoparticle-mediated delivery, achieving over 88 % cumulative drug release within 30 days and effectively covering the critical postoperative recurrence window. • 2. Curcumin exerts a “three-in-one” synergistic effect by enhancing TMZ chemosensitivity, suppressing glioma stem cell stemness via JAK-STAT pathway inhibition, and reprogramming the tumor microenvironment through metabolic and immune modulation. • 3. The ROS- and thermo-sensitive gel system enables localized, responsive drug delivery within the resection cavity, significantly extending median survival to 57 days (3 × control) while minimizing systemic toxicity, as validated by multi-omics and in vivo studies.

Source: International Journal of Pharmaceutics X

DOI: 10.1016/j.ijpx.2025.100418

Authors: Qiong Liang, Jiangjian Liu, Yanhang Zhuo, Sunhui Chen

Institutions: Fujian Medical University, Fuzhou University

Language: English

Topic: Glioma Diagnosis and Treatment

Subfield: Genetics

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,590