Plate-like Alginate Microparticles with Disulfiram-SPIO-Coencapsulation: An In Vivo Study for Combined Therapy on Ovarian Cancer

双硫仑-超顺磁性氧化铁共包覆板状海藻酸盐微粒:卵巢癌联合治疗的体内研究

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作者:Meng-Yi Bai, Mu-Hsien Yu, Ting-Teng Wang, Shiu-Hsin Chen, Yu-Chi Wang

Abstract

Disulfiram is a drug used to support the treatment of chronic alcoholism. Recently, it has been found to have an off-label ability to inhibit the growth of ovarian cancer cells. However, the original formulation was designed for use via oral administration, which is not suitable to be given by a direct spray on the affected area. Therefore, in this study, we designed and prepared alginate (ALG) microparticles loaded with disulfiram and superparamagnetic iron oxide (cross-linking disulfiram/SPIO/ALG MPs), which have great potential application for inhibiting the growth of ovarian cancer simultaneously via two treatments, i.e., chemotherapy and hyperthermia. The drug-encapsulating alginate microparticles were prepared using an electrospray system and then cross-linked with calcium chloride ions. The particles were observed by optical microscopy and scanning electron microscopy, and found to be approximately 200 μm in diameter. The disc-shape morphology of the microparticles could be controlled by up to 95%. The drug-encapsulation efficiency of the microparticles reached 98%, and the suppression of tumor growth for the free-form disulfiram-treated group and disulfiram/SPIO/ALG MPs-treated group were 48.2% and 55.9% of tumor volume reduction, respectively, compared with a cisplatin-treated group. A hyperthermic effect can be achieved by applying a magnetic field to oscillate SPIO. The results of this study showed that these cross-linking disulfiram/SPIO/ALG MPs are potential drug carriers for the treatment of ovarian cancer.

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