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.

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.