Preliminary Assessment of Repurposed Mebendazole Nano-Systems for Passive Targeting and Potential Treatment of Bone Metastasis

Bone metastasis is commonly observed in cancer patients, necessitating high-dose chemotherapy for effective treatment. Despite its challenging physicochemical properties, repurposing mebendazole (Meb) has shown promise in inhibiting cancer progression. To overcome its poor solubility and enhance tumor targeting, nanocrystals were employed as a delivery platform. Therefore, the current work aimed to develop optimized Meb nanocrystals with improved bone metastasis therapeutic potential via passive targeting. Optimization was achieved through high shear homogenization and stabilizer selection (HPMC E15) to produce nanocrystals with enhanced colloidal stability and size uniformity. In-vitro characterization and in-vivo assessment were conducted to compare the selected optimized formulation with the Meb solution. Two Meb nanocrystal formulations, homogenized (NC4) and unhomogenized (NC*), were compared to determine the importance of particle size reduction. Results revealed that NC4, prepared using anti-solvent precipitation combined with high shear homogenization, exhibited a promising particle size (121.20 ± 6.20 nm) and higher drug release in the acidic pH, favorable for passive targeting. Furthermore, the in vivo results confirmed the superior effects on tumor growth inhibition (90.01%), pain remission, and bone tumor markers of NC4 over NC*. Finally, NC4 showed an absence of kidney and liver toxicity. In conclusion, these comprehensive findings strongly support the clinical relevance of NC4 in treating bone metastasis. Its ability to passively target the drug, inhibit tumor growth, alleviate pain, and exhibit favorable biomarker profiles and safety make it a promising candidate for improving the management and outcomes of patients with bone metastasis.