Nasal Delivery of Nanoemulsion Containing a Synergistic Combination of Curcumin and Gefitinib for Brain Tumor Targeting

Objectives: This study involves combination therapy of anticancer drugs (curcumin and gefitinib) as nanoemulsion and their application for treating human glioblastoma U373MG cell lines. Materials and Methods: Nanoemulsions containing the synergistic combination were prepared using a high-pressure homogenization technique. Nanoemulsion formulation was characterized for globule size, drug content, thermodynamic stability, zeta potential measurement and drug release. Histological studies were performed using isolated nasal mucosa of sheep. Results: The combination was found to be synergistic as they were more effective in inhibiting the growth or viability of the U373MG glioblastoma cells compared to using each drug individually. The lowest Combination Index (CI) value of 0.2 indicates a strong synergistic effect. A CI value less than 1 generally suggests synergy, meaning that the combined effect of the drugs is greater than what would be expected if they were simply additive. Both drug concentrations in the brain were significantly higher after IN administration of CRM-GFT-NE compared to IV administration of PDS. Drug targeting efficiency and direct nose-to-brain transport following intranasal administration of optimized CRM-GFT-NE were 1871.26±2.56 and 95.21±0.93 for CRM and 1807.95±5.11 and 93.52±0.63 for GFT respectively. Conclusion: The study used a passive targeting approach as nanocarriers to improve the delivery of CRM and GFT to the tumor cells. This suggests that the drugs were engineered or formulated to specifically target the cancer cells, potentially reducing dose-related side effects. The study also demonstrated a high percentage of nose-to-brain drug transport for both CRM and GFT. This implies that the optimized Nanoemulsions (NEs) used in the study effectively delivered the drugs to the Central Nervous System (CNS) via the intranasal route. This is crucial for treating glioblastoma, as it requires drugs to cross the blood-brain barrier and reach the tumor in the brain. In summary, this study indicates that the combination of curcumin and gefitinib has a strong synergistic effect in inhibiting glioblastoma cell growth. Additionally, the use of targeted drug delivery systems, specifically designed to transport the drugs to the brain, was successful in achieving effective CNS targeting. These findings suggest nanoemulsion formulation as a promising approach for the treatment of glioblastoma with reduced systemic side effects.