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

TL;DR

A new drug delivery system using a gel that releases medication in two phases helps prevent glioma recurrence after surgery by using curcumin's multiple effects.

Contribution

A ROS- and thermo-sensitive gel system with biphasic drug release and curcumin's 'three-in-one' effect is developed for localized postoperative glioma treatment.

Findings

The gel system achieved over 88% drug release within 30 days and extended rat survival threefold.

Curcumin enhanced temozolomide's effectiveness, inhibited glioma stem cells, and altered the tumor microenvironment.

The system reduced systemic toxicity while targeting DNA repair and metabolic pathways.

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.Unlabelled Image

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 and sustained release.•2. Curcumin exerts a “three-in-one” synergism by enhancing chemosensitivity, inhibiting GSCs, and reprogramming TME.•3. The ROS- and thermo-sensitive gel system enables localized, responsive drug delivery within the resection cavity.

1. A biphasic drug-release postoperative in situ gel system was developed, integrating rapid and sustained release.

2. Curcumin exerts a “three-in-one” synergism by enhancing chemosensitivity, inhibiting GSCs, and reprogramming TME.

3. The ROS- and thermo-sensitive gel system enables localized, responsive drug delivery within the resection cavity.

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