Objective:

To enhance curcumin’s delivery and therapeutic efficacy against GBM using a hydroxypropyl-beta-cyclodextrin (HPβCD) nanoparticle formulation.

Background:

Glioblastoma (GBM) is the most aggressive primary brain tumor with limited treatment options and poor prognosis. Curcumin exhibits potent anticancer effects through modulation of autophagy and AMPK/mTOR signaling but is hindered by poor solubility, instability, and limited cellular uptake, restricting clinical translation.

Design/Methods:

HPβCD-curcumin nanoparticles (HPβCD-Curcumin) were synthesized and encapsulation confirmed by Nuclear Magnetic Resonance (NMR). U251 human GBM cells were assessed for cytotoxicity, migration (wound-healing), clonogenic survival, and intracellular uptake (fluorescence microscopy). In vitro assays were conducted in triplicate (migration, clonogenic) or quintuplicate (viability), and in vivo efficacy was evaluated by Magnetic Resonance Imaging (MRI) in rats (n = 4 per group) implanted with U251 tumors. Statistical significance was determined using one-way ANOVA with Tukey’s post hoc test.

Results:

HPβCD-Curcumin significantly improved solubility and stability compared with free curcumin. At 20 µM for 48 hours, cell viability decreased by ~55% with HPβCD-Curcumin versus ~30% with free curcumin (p < 0.001; n = 5). Cellular uptake increased ~2.1-fold. Wound closure was reduced by ~70% compared with ~40% for free curcumin (p < 0.01; n = 3), and clonogenic survival decreased by ~80% versus ~50% (p < 0.01; n = 3). In vivo MRI showed a ~65% reduction in tumor volume with HPβCD-Curcumin treatment compared with ~25% for free curcumin (p < 0.01; n = 4).

Conclusions:

HPβCD-Curcumin nanoparticles enhance curcumin’s cytotoxic, anti-migratory, and tumor-suppressive activities, achieving superior in vitro and in vivo efficacy versus free curcumin. These results support HPβCD-Curcumin as a rationally designed nanomedicine with strong translational potential for glioblastoma therapy.