Hansapaiboon Supakarn, Bulatao Bryan Paul, Sorasitthiyanukarn Feuangthit Niyamissara, Jantaratana Pongsakorn, Nalinratana Nonthaneth, Vajragupta Opa, Rojsitthisak Pranee, Rojsitthisak Pornchai
Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand.
Pharmaceutical Sciences and Technology Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Polymers (Basel). 2022 Dec 19;14(24):5563. doi: 10.3390/polym14245563.
This study shows the effectiveness of magnetic-guide targeting in the delivery of curcumin diethyl γ-aminobutyrate (CUR-2GE), a prodrug of curcumin (CUR) previously synthesized to overcome unfavorable physicochemical properties of CUR. In this study, chitosan (Ch)-coated iron oxide nanoparticles (Ch-IONPs) were fabricated and optimized using Box-Behnken design-based response surface methodology for delivery of CUR-2GE. Ch was used as a coating material on the nanoparticle surface to avoid aggregation. The optimized condition for preparing Ch-IONPs consisted of using 4 mg Ch fabricated at pH 11 under a reaction temperature of 85 °C. The optimized Ch-IONPs were successfully loaded with CUR-2GE with sufficient loading capacity (1.72 ± 0.01%) and encapsulation efficiency (94.9 ± 0.8%). The obtained CUR-2GE-loaded Ch-IONPs (CUR-2GE-Ch-IONPs) exhibited desirable characteristics including a particle size of less than 50 nm based on TEM images, superparamagnetic property, highly crystalline IONP core, sufficient stability, and sustained-release profile. In the presence of permanent magnets, CUR-2GE-Ch-IONPs significantly increased cellular uptake and cytotoxicity toward MDA-MB-231 with a 12-fold increase in potency compared to free CUR-2GE, indicating the potential of magnetic-field assisted delivery of CUR-2GE-Ch-IONPs for the treatment of triple-negative breast cancer.
本研究显示了磁导向靶向在姜黄素二乙氨基丁酸盐（CUR-2GE）递送中的有效性，姜黄素二乙氨基丁酸盐是姜黄素（CUR）的一种前药，此前已合成以克服CUR不利的物理化学性质。在本研究中，使用基于Box-Behnken设计的响应面方法制备并优化了壳聚糖（Ch）包被的氧化铁纳米颗粒（Ch-IONPs）用于CUR-2GE的递送。Ch被用作纳米颗粒表面的包被材料以避免聚集。制备Ch-IONPs的优化条件包括在85℃的反应温度下，使用在pH 11条件下制备的4mg Ch。优化后的Ch-IONPs成功负载了CUR-2GE，具有足够的负载量（1.72±0.01%）和包封率（94.9±0.8%）。基于透射电镜图像，所获得的负载CUR-2GE的Ch-IONPs（CUR-2GE-Ch-IONPs）表现出理想的特性，包括粒径小于50nm、超顺磁性、高度结晶的IONP核心、足够的稳定性和缓释特性。在永磁体存在的情况下，CUR-2GE-Ch-IONPs显著增加了对MDA-MB-231细胞的摄取和细胞毒性，其效力比游离CUR-2GE增加了12倍，表明CUR-2GE-Ch-IONPs的磁场辅助递送在治疗三阴性乳腺癌方面具有潜力。
