College of Pharmacy, Idaho State University, Pocatello, ID 83209, USA.
Mar Drugs. 2022 Aug 10;20(8):509. doi: 10.3390/md20080509.
Sphingomyelin is a cell membrane sphingolipid that is upregulated in synovial sarcoma (SS). Jaspine B has been shown to inhibit sphingomyelin synthase, which synthesizes sphingomyelin from ceramide, a critical signal transducer; however, jaspine B's low bioavailability limits its application as a promising treatment option. To address this shortcoming, we used microfluidics to develop a liposomal delivery system with increased anticancer efficacy. The nano-liposome size was determined by transmission electron microscopy. The jaspine B liposome was tested for its tumor inhibitory efficacy compared to plain jaspine B in in vitro and in vivo studies. The human SS cell line was tested for cell viability using varying jaspine B concentrations. In a mouse model of SS, tumor growth suppression was evaluated during four weeks of treatment (3 times/week). The results show that jaspine B was successfully formulated in the liposomes with a size ranging from 127.5 ± 61.2 nm. The MTT assay and animal study results indicate that jaspine B liposomes dose-dependently lowers cell viability in the SS cell line and effectively suppresses tumor cell growth in the SS animal model. The novel liposome drug delivery system addresses jaspine B's low bioavailability issues and improves its therapeutic efficacy.
鞘磷脂是一种细胞膜鞘脂,在滑膜肉瘤(SS)中上调。Jaspine B 已被证明能抑制鞘磷脂合酶,后者将神经酰胺合成鞘磷脂,神经酰胺是一种关键的信号转导物;然而,Jaspine B 的生物利用度低限制了其作为一种有前途的治疗选择的应用。为了解决这个缺点,我们使用微流控技术开发了一种具有增强抗癌功效的脂质体递送系统。纳米脂质体的大小通过透射电子显微镜确定。与普通 Jaspine B 相比,我们在体外和体内研究中测试了 Jaspine B 脂质体的肿瘤抑制功效。使用不同浓度的 Jaspine B 测试人滑膜肉瘤细胞系的细胞活力。在滑膜肉瘤的小鼠模型中,在 4 周的治疗期间(每周 3 次)评估肿瘤生长抑制情况。结果表明,Jaspine B 成功地包封在脂质体中,其大小范围为 127.5±61.2nm。MTT 检测和动物研究结果表明,Jaspine B 脂质体剂量依赖性地降低滑膜肉瘤细胞系中的细胞活力,并有效地抑制滑膜肉瘤动物模型中的肿瘤细胞生长。这种新型脂质体药物递送系统解决了 Jaspine B 的生物利用度低的问题,并提高了其治疗功效。