Colorectal cancer with peritoneal metastasis has a poor prognosis because of inadequate responses to systemic chemotherapy. Cytoreductive surgery followed by intraperitoneal (IP) chemotherapy using oxaliplatin has attracted attention; however, the short half-life of oxaliplatin and its rapid clearance from the peritoneal cavity limit its clinical application. Here, a multivesicular liposomal (MVL) depot of oxaliplatin was prepared for IP administration, with an expected prolonged effect. After optimization, a combination of phospholipids, cholesterol, and triolein was used based on its ability to produce MVL depots of monomodal size distribution (1–20 µm; span 1.99) with high entrapment efficiency (EE) (92.16% ± 2.17%). An initial burst release followed by a long lag phase of drug release was observed for the MVL depots system in vitro. An in vivo pharmacokinetic study mimicking the early postoperative IP chemotherapy regimen in rats showed significantly improved bioavailability, and the mean residence time of oxaliplatin after IP administration revealed that slow and continuous erosion of the MVL particles yielded a sustained drug release. Thus, oxaliplatin-loaded MVL depots presented in this study have potential for use in the treatment of colorectal cancer.

中文翻译：

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腹膜内长效奥沙利铂负载的多囊脂质体贮库的制备和评价。

大肠癌伴腹膜转移的预后较差，因为对全身化疗的反应不足。使用奥沙利铂进行的细胞减低手术以及腹膜内（IP）化疗引起了人们的关注。然而，奥沙利铂的半衰期短和其从腹膜腔的快速清除限制了其临床应用。在此，制备了奥沙利铂的多囊脂质体（MVL）储库用于IP给药，具有预期的延长效果。经过优化后，基于磷脂，胆固醇和三油精的产生具有单峰尺寸分布（1–20 µm；跨度1.99）的MVL库的能力，并结合了高包封率（EE）（92.16％±2.17％），将其组合使用。对于体外MVL贮库系统，观察到最初的突释释放和随后的长时间的药物释放滞后阶段。一项模拟大鼠术后早期IP化疗方案的体内药代动力学研究显示，其生物利​​用度显着提高，IP给药后奥沙利铂的平均停留时间显示，MVL颗粒缓慢而持续的侵蚀可产生持续的药物释放。因此，本研究中介绍的载有奥沙利铂的MVL储库在治疗结直肠癌方面具有潜力。