Abstract：
Aim: The current study aims to develop and optimize microemulsions (ME) through Quality-by-Design (QbD) approach to improve the aqueous solubility and dissolution of poorly water-soluble drug disulfiram (DSF) for repurposing in melanoma and breast cancer therapy. Materials & methods: The ME was formulated using Cinnamon oil & Tween® 80, statistically optimized using a D-optimal mixture design-based QbD approach to develop the best ME with low vesicular size (Zavg) and polydispersity index (PDI). Results: The DSF-loaded optimized stable ME showed enhanced dissolution, in-vitro cytotoxicity and improved cellular uptake in B16F10 and MCF-7 cell lines compared with their unformulated free DSF. Conclusion: Our investigations suggested the potential of the statistically designed DSF-loaded optimized ME for repurposing melanoma and breast cancer therapy.
Identifying new medicinal uses of an existing marketed drug can save both money and time in the process of drug development. From many of the recently reported literature, disulfiram (a drug used for alcoholism) has shown its activity against various cancers, including breast and skin cancer. However, it possesses poor water solubility and absorption, leading to low medicinal activity. The current study aims to develop a novel microemulsion dosage form through a statistical design approach to enhance the solubility, dissolution and anticancer activity for repurposing in melanoma and breast cancer treatment. The novel microemulsion was prepared, statistically analyzed and optimized. The optimized microemulsion was found to be stable and showed improved medicinal activity against breast and skin cancer compared with the pure drug. Our research showed the potential of the developed microemulsion of the disulfiram for its new therapeutic use in skin cancer and breast cancer.
Identifying new medicinal uses of an existing marketed drug can save both money and time in the process of drug development. From many of the recently reported literature, disulfiram (a drug used for alcoholism) has shown its activity against various cancers, including breast and skin cancer. However, it possesses poor water solubility and absorption, leading to low medicinal activity. The current study aims to develop a novel microemulsion dosage form through a statistical design approach to enhance the solubility, dissolution and anticancer activity for repurposing in melanoma and breast cancer treatment. The novel microemulsion was prepared, statistically analyzed and optimized. The optimized microemulsion was found to be stable and showed improved medicinal activity against breast and skin cancer compared with the pure drug. Our research showed the potential of the developed microemulsion of the disulfiram for its new therapeutic use in skin cancer and breast cancer.
摘要：
目的：本研究旨在通过设计质量（QbD）方法开发和优化微乳剂（ME），以改善水溶性差的药物双硫仑（DSF）的水溶性和溶出度，用于黑色素瘤和乳腺癌治疗。材料和方法:使用肉桂油和Tween®80配制ME,使用基于D-最佳混合物设计的QbD方法进行统计学优化,以开发具有低囊泡尺寸(Zavg)和多分散指数(PDI)的最佳ME。结果：DSF负载优化的稳定ME显示出溶出增强，与未配制的游离DSF相比，B16F10和MCF-7细胞系的体外细胞毒性和细胞摄取改善。结论：我们的研究表明，经统计学设计的DSF加载优化的ME用于重新利用黑色素瘤和乳腺癌治疗的潜力。
确定现有上市药物的新药物用途可以在药物开发过程中节省金钱和时间。从最近报道的许多文献中，双硫仑（一种用于酒精中毒的药物）已显示出其对各种癌症的活性，包括乳腺癌和皮肤癌.然而,它具有较差的水溶性和吸收性，导致低药用活性。当前的研究旨在通过统计设计方法开发一种新型的微乳剂剂型，以提高溶解度，用于黑色素瘤和乳腺癌治疗的溶解和抗癌活性。制备了新型微乳液,统计分析和优化。与纯药物相比，优化的微乳剂稳定，并显示出对乳腺癌和皮肤癌的药物活性。我们的研究表明，开发的双硫仑微乳剂在皮肤癌和乳腺癌中的新治疗用途具有潜力。
确定现有上市药物的新药物用途可以在药物开发过程中节省金钱和时间。从最近报道的许多文献中，双硫仑（一种用于酒精中毒的药物）已显示出其对各种癌症的活性，包括乳腺癌和皮肤癌.然而,它具有较差的水溶性和吸收性，导致低药用活性。当前的研究旨在通过统计设计方法开发一种新型的微乳剂剂型，以提高溶解度，用于黑色素瘤和乳腺癌治疗的溶解和抗癌活性。制备了新型微乳液,统计分析和优化。与纯药物相比，优化的微乳剂稳定，并显示出对乳腺癌和皮肤癌的药物活性。我们的研究表明，开发的双硫仑微乳剂在皮肤癌和乳腺癌中的新治疗用途具有潜力。
