Reichel Derek, Lee Min Jae, Lee Wooin, Kim Kyung Bo, Bae Younsoo
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, Lexington, KY 40536-0596, USA.
College of Pharmacy, Seoul National University, 1 Gwanak-Ro, Gwanak-Gu, Seoul 151-742, Korea.
Ther Deliv. 2016 Oct;7(10):665-681. doi: 10.4155/tde-2016-0041.
Proteasome inhibitors, such as carfilzomib (CFZ), have shown potential to treat various types of cancers in preclinical models, but clinical applications are limited likely due to formulation and delivery issues. Results & methodology: Tethered polymer nanoassemblies (TNAs) were synthesized by tethering hydrophilic polymers and hydrophobic groups to charged polymer scaffolds, and then end-capping remaining amines on scaffold. Drug entrapment and drug release half-lives increased as charge was removed from scaffold. TNAs with sustained CFZ release maintained drug efficacy after preincubation and increased duration of proteasome inhibition in cancer cells compared with free CFZ.
TNAs fine-tuned CFZ release as charge was removed from polymer scaffold, which allowed for sustained proteasome inhibition in cancer cells and potentially enhanced anticancer efficacy.
蛋白酶体抑制剂，如卡非佐米（CFZ），在临床前模型中已显示出治疗各种类型癌症的潜力，但由于制剂和递送问题，其临床应用受到限制。结果与方法：通过将亲水性聚合物和疏水性基团连接到带电聚合物支架上，然后封闭支架上剩余的胺基，合成了 tethered 聚合物纳米组装体（TNA）。随着支架上电荷的去除，药物包封率和药物释放半衰期增加。与游离 CFZ 相比，具有持续 CFZ 释放的 TNA 在预孵育后保持药物疗效，并延长了癌细胞中蛋白酶体抑制的持续时间。
随着聚合物支架上电荷的去除，TNA 对 CFZ 释放进行了微调，这使得癌细胞中的蛋白酶体能够持续受到抑制，并可能增强抗癌疗效。
