Curcumin combining temozolomide formed localized nanogel for inhibition of postsurgical chemoresistant glioblastoma

Plain language summaryIn this study, the animal model used was rats suffering residual brain tumor after resection. The selected drugs were temozolomide, a first-line chemotherapeutic drug for the clinical treatment of glioma, and curcumin, an extract from the ginger plant. With the use of temozolomide, brain glioma cells gradually develop resistance, resulting in poor efficacy of temozolomide. Therefore, the purpose of this study was to construct a drug-delivery system for temozolomide-resistant brain glioma residual tumor after surgery, namely, a temperature-sensitive gel containing drug-carrying nanopreparations - the so-called nanogels. This drug-delivery system can directly deliver drugs to residual tumor cells in situ after surgery. In situ drug-delivery systems can reduce the dose of drugs consumed and increase their potency compared to oral or intravenous administration. Aim: To investigate the use of nanoparticle (NP)-encapsulated injectable thermosensitive hydrogel-formed nanogel for inhibition of postsurgical residual temozolomide (TMZ)-resistant glioblastoma (GBM) recurrence. Materials & methods: Curcumin (Cur) was coloaded with TMZ into PEG-PLGA NPs, then NPs were further encapsulated into a thermosensitive hydrogel to form a nanogel, which was injected into the resection cavity of the GBM postsurgery. Results: The prepared nanogel displayed excellent drug-loading capacity and long-term drug release. Estimated survival characteristics demonstrated that the nanogel could play a significant role in TMZ-resistant tumor inhibition with low drug-induced toxicity. The originally designed ratio of Cur/TMZ was sustained, making it an effective therapeutic outcome. Conclusion: Cur-combined TMZ-formed nanogels can be a promising candidate for the local inhibition of GBM recurrence.