Despite the success in exploring and repurposing of its various biological efficacies such as antitumor and others, disulfiram (DSF), a copper-dependent antitumor drug, suffers from multiple shortcomings of poor aqueous solubility and instability in the physiological environment, which often hinder its clinical applicability. Moreover, the limited availability of copper in the body also hampered the therapeutic ability of DSF. Initially, the determined experimental solubility values of DSF (7.89 × 10⁻⁵ to 6.71 × 10^-4 mole fraction) in supercritical carbon dioxide (SC−CO₂) at different critical conditions are subsequently correlated using various empirical models. Further, the sub-micronized products of DSF (with mean diameters ranging from 1.53 ± 0.45 to 0.62 ± 0.11 μm) and its subsequent DSF-copper complexes (CuET) (with mean diameters ranging from 1.45 ± 0.45 to 0.27 ± 0.06 μm) are fabricated using the rapid expansion of supercritical solutions (RESS) process. Further, the suspension ability of these complexes is improved by coating with polyvinylpyrrolidone (PVP) and methoxy b-poly(_L-lactide) 2000- poly(ethylene glycol) 2000 (mPLLA-PEG) solution using the RESS-based processes that with the different receiving mediums. The physicochemical properties and dissolution profiles of these composites are systematically recorded. in vitro anti-proliferation studies confirmed the substantial augmentation of bioefficacy of micronized DSF in the presence of copper. Moreover, the polymer-coated DSF or CuET nanoparticles significantly enhanced the toxicity of DSF, attributing to their relatively smaller sizes and excellent dispersibility in the aqueous environment. Thus, our findings showed that the altered dissolution rate of drugs and the synergistic effect of the metal species in CuET complex significantly amplified the antitumor efficacy of DSF, indicating the potential of RESS process in enhancing the dissolution rate as well as substantial antitumor efficiency of nano-sized drugs and their complexes.

尽管成功探索并重新利用了其多种生物功效，例如抗肿瘤药和其他药物，但是铜依赖性抗肿瘤药双硫仑（DSF）却存在多种缺点，即水溶性差，在生理环境中不稳定，这常常会阻碍其临床应用。适用性。此外，体内铜的有限可用性也阻碍了DSF的治疗能力。最初，确定的DSF在超临界二氧化碳（SC-CO _2中）的实验溶解度值（7.89×10 ^-5至6.71×10 ^-4摩尔分数）随后使用各种经验模型将不同临界条件下的）关联起来。此外，DSF（平均直径范围为1.53±0.45至0.62±0.11μm）的亚微粉化产物及其后续的DSF-铜复合物（CuET）（平均直径范围为1.45±0.45至0.27±0.06μm）为使用超临界解决方案（RESS）工艺的快速扩展制造而成。此外，这些复合物的悬浮能力可以通过使用基于RESS的方法用聚乙烯吡咯烷酮（PVP）和甲氧基b-聚（_L-丙交酯）2000-聚（乙二醇）2000（mPLLA-PEG）溶液进行涂覆来提高。不同的接收介质。系统地记录了这些复合材料的物理化学性质和溶出曲线。体外抗扩散研究证实，在铜存在下，微粉化DSF的生物功效大大提高。此外，聚合物涂覆的DSF或CuET纳米颗粒显着增强了DSF的毒性，这归因于其相对较小的尺寸和在水性环境中的优异分散性。因此，我们的研究结果表明，改变药物的溶出速率和金属离子在CuET络合物中的协同作用显着增强了DSF的抗肿瘤功效，表明RESS工艺在提高纳米颗粒的溶出速率以及显着的抗肿瘤效率方面具有潜力药物及其复合物。