Department of Pharmacy, the First Hospital of China Medical University, Shenyang, Liaoning, PR China; School of Pharmacy, China Medical University, Shenyang, Liaoning, PR China.
Department of Biotherapy, Cancer Research Institute, the First Hospital of China Medical University, Shenyang, Liaoning, PR China.
Colloids Surf B Biointerfaces. 2023 Nov;231:113558. doi: 10.1016/j.colsurfb.2023.113558. Epub 2023 Sep 18.
To develop a long-term drug delivery system for the treatment of primary and metastatic peritoneal carcinoma (PC) by intraperitoneal (IP) injection, a disulfiram (DSF)/copper gluconate (Cu-Glu)-co-loaded bi-layered poly (lactic acid-coglycolic acid) (PLGA) microspheres (Ms) - thermosensitive hydrogel system (DSF-Ms-Cu-Glu-Gel) was established. Rate and mechanisms of drug release from DSF-Ms-Cu-Glu-Gel were explored. The anti-tumor effects of DSF-Ms-Cu-Glu-Gel by IP injection were evaluated using H22 xenograft tumor model mice. The accumulative release of DSF from Ms on the 10th day was 83.79% without burst release. When Ms were dispersed into B-Gel, burst release at 24 h decreased to 14.63%. The results showed that bis (diethyldithiocarbamate)-copper (Cu(DDC)) was formed in DSF-Ms-Cu-Glu-Gel and slowly released from B-Gel. In a pharmacodynamic study, the mount of tumor nodes and ascitic fluid decreased in the DSF-Ms-Cu-Glu-Gel group. This was because: (1) DSF-Ms-Cu-Glu-Gel system co-loaded DSF and Cu-Glu, and physically isolated DSF and Cu-Glu before injection to protect DSF; (2) space and water were provided for the formation of Cu(DDC); (3) could provide an effective drug concentration in the abdominal cavity for a long time; (4) both DSF and Cu(DDC) were effective anti-tumor drugs, and the formation of Cu(DDC) occurred in the abdominal cavity, which further enhanced the anti-tumor activity. Thus, the DSF-Ms-Cu-Glu-Gel system can be potentially used for the IP treatment of PC in the future.
为了开发一种用于治疗原发性和转移性腹膜癌（PC）的腹腔内（IP）注射长效药物递送系统，通过 IP 注射建立了载有双硫仑（DSF）/葡萄糖酸铜（Cu-Glu）的双层聚（乳酸-共-乙醇酸）（PLGA）微球（Ms）-温敏水凝胶系统（DSF-Ms-Cu-Glu-Gel）。探讨了 DSF-Ms-Cu-Glu-Gel 的药物释放速率和机制。通过 H22 异种移植肿瘤模型小鼠评估了 DSF-Ms-Cu-Glu-Gel 通过 IP 注射的抗肿瘤作用。载有 DSF 和 Cu-Glu 的 Ms 在第 10 天的累积释放量为 83.79%，无突释。当 Ms 分散到 B-Gel 中时，24 h 时的突释量减少到 14.63%。结果表明，DSF-Ms-Cu-Glu-Gel 中形成了双（二乙基二硫代氨基甲酸盐）-铜（Cu（DDC）），并从 B-Gel 中缓慢释放。在药效学研究中，DSF-Ms-Cu-Glu-Gel 组肿瘤结节和腹水的数量减少。这是因为：（1）DSF-Ms-Cu-Glu-Gel 系统共载有 DSF 和 Cu-Glu，在注射前物理隔离 DSF 和 Cu-Glu 以保护 DSF；（2）为 Cu（DDC）的形成提供空间和水；（3）可以在腹腔内长时间提供有效的药物浓度；（4）DSF 和 Cu（DDC）都是有效的抗肿瘤药物，Cu（DDC）在腹腔内形成，进一步增强了抗肿瘤活性。因此，DSF-Ms-Cu-Glu-Gel 系统将来可潜在用于 PC 的 IP 治疗。
