The clinical application of disulfiram (DSF) in cancer treatments is hindered by its rapid degradation in the blood circulation. In this study, methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide)/poly(ε-caprolactone) (mPEG_5k-b-PLGA_2k/PCL_3.4k) micelles were developed for encapsulation of DSF by using the emulsification–solvent diffusion method. Medium chain triglyceride (MCT) was incorporated into the mixed polymeric micelles to improve drug loading by reducing the core crystallinity. Differential scanning calorimetry (DSC) results implied that DSF is likely present in an amorphous form within the micelles, and is well dispersed. DSF is encapsulated within the core and the reservoir is stabilized by the hydrophilic shell to prevent rapid diffusion of DSF from the core. The DSF mixed micelles (DSF-MMs) showed good drug loading (5.90%) and a well-controlled particle size (86.4 ± 13.2 nm). The mixed micelles efficiently protected DSF from degradation in plasma, with 58% remaining after 48 h, while almost 90% of DSF was degraded after the same period for the DSF solution (DSF-sol), which was used as a control. The pharmacokinetics study showed that the maximum plasma concentration and bioavailability of DSF were improved by using the DSF-MMs (2 and 2.5 times that of the DSF-sol). The TIRs (tumor inhibition rates) of 5-FU, DSF-sol, and DSF-MMs were 63.46, 19.57, and 69.98%, respectively, implying that DSF-MMs slowed the growth of a H22 xenograft tumor model effectively.

中文翻译：

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mPEG _5k - b -PLGA _2k / PCL _3.4k / MCT混合胶束作为双硫仑的载体，可改善体内血浆稳定性和抗肿瘤作用

双硫仑（DSF）在血液循环中的快速降解阻碍了其在癌症治疗中的临床应用。在这项研究中，甲氧基聚（乙二醇）-b-聚（丙交酯-共-乙交酯）/聚（ε-己内酯）（mPEG _5k - b -PLGA _2k / PCL _3.4k）通过使用乳化-溶剂扩散法开发了胶束，用于DSF的封装。将中链甘油三酸酯（MCT）掺入混合的聚合物胶束中，以通过降低核心结晶度来提高药物负载量。差示扫描量热法（DSC）的结果表明，DSF可能以无定形形式存在于胶束中，并且分散良好。DSF包封在岩心中，而储层由亲水壳层稳定，以防止DSF从岩心快速扩散。DSF混合胶束（DSF-MMs）表现出良好的载药量（5.90％）和良好控制的粒径（86.4±13.2 nm）。混合的胶束有效地保护了DSF免受血浆降解，在48小时后仍保留58％，而对于DSF溶液（DSF-sol），在同一时期后几乎有90％的DSF被降解，用作对照。药代动力学研究表明，使用DSF-MM可以提高DSF的最大血浆浓度和生物利用度（是DSF-sol的2倍和2.5倍）。5-FU，DSF-sol和DSF-MM的TIR（肿瘤抑制率）分别为63.46、19.57和69.98％，这表明DSF-MM有效地减缓了H22异种移植肿瘤模型的生长。