Preparation, Optimization, and In-Vitro Evaluation of Brusatol- and Docetaxel-Loaded Nanoparticles for the Treatment of Prostate Cancer.
Preparation, Optimization, and In-Vitro Evaluation of Brusatol- and Docetaxel-Loaded Nanoparticles for the Treatment of Prostate Cancer.
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DOI：
10.3390/pharmaceutics16010114
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发表时间：
2024-01-16
期刊：
影响因子：
5.4
通讯作者：
Adesina SK
中科院分区：
文献类型：
--
作者：
Adekiya TA;Moore M;Thomas M;Lake G;Hudson T;Adesina SK
多西他赛用于前列腺癌治疗的挑战包括几种耐药机制以及毒性。为了克服这些挑战并提高异质性前列腺癌的治疗效果，需要使用可以破坏肿瘤不同亚群的多种药物。多靶点抑制剂曲马多具有较强的抗肿瘤活性，并在药物应答和耐药性中发挥重要作用。因此，用于治疗前列腺癌的纳米颗粒平台中的布鲁沙醇和多西他赛的组合预期产生协同效应。在这项研究中，我们报告了聚合物纳米颗粒的发展，用于治疗前列腺癌的布鲁沙托和多西他赛的交付。使用单因素一次法筛选影响粒度的处方和工艺变量。随后，使用24全析因统计实验设计评价了对粒度具有可变影响的因素，然后优化了载药量。空白纳米颗粒的优化得到平均尺寸为169.1 nm ± 4.8 nm的制剂，与预测尺寸168.333 nm一致。透射电子显微镜显示光滑的球形纳米粒子。药物释放曲线显示包封的药物在24 h内释放。联合指数数据显示药物之间存在协同相互作用。细胞周期分析和半胱天冬酶活性的评价显示PC-3和LNCaP前列腺癌细胞对试剂的反应存在差异。此外，免疫印迹显示在用不同试剂和制剂处理24小时和72小时后LNCaP细胞中存活素表达的差异。因此，纳米颗粒可能适用于晚期前列腺癌的治疗。
Challenges to docetaxel use in prostate cancer treatment include several resistance mechanisms as well as toxicity. To overcome these challenges and to improve the therapeutic efficacy in heterogeneous prostate cancer, the use of multiple agents that can destroy different subpopulations of the tumor is required. Brusatol, a multitarget inhibitor, has been shown to exhibit potent anticancer activity and play an important role in drug response and chemoresistance. Thus, the combination of brusatol and docetaxel in a nanoparticle platform for the treatment of prostate cancer is expected to produce synergistic effects. In this study, we reported the development of polymeric nanoparticles for the delivery of brusatol and docetaxel in the treatment of prostate cancer. The one-factor-at-a-time method was used to screen for formulation and process variables that impacted particle size. Subsequently, factors that had modifiable effects on particle size were evaluated using a 24 full factorial statistical experimental design followed by the optimization of drug loading. The optimization of blank nanoparticles gave a formulation with a mean size of 169.1 nm ± 4.8 nm, in agreement with the predicted size of 168.333 nm. Transmission electron microscopy showed smooth spherical nanoparticles. The drug release profile showed that the encapsulated drugs were released over 24 h. Combination index data showed a synergistic interaction between the drugs. Cell cycle analysis and the evaluation of caspase activity showed differences in PC-3 and LNCaP prostate cancer cell responses to the agents. Additionally, immunoblots showed differences in survivin expression in LNCaP cells after treatment with the different agents and formulations for 24 h and 72 h. Therefore, the nanoparticles are potentially suitable for the treatment of advanced prostate cancer.
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DOI：
10.1016/b978-0-12-814033-8.00004-7
发表时间：
2019-01-01
期刊：
NANOCARRIERS FOR DRUG DELIVERY: NANOSCIENCE AND NANOTECHNOLOGY IN DRUG DELIVERY
影响因子：
--
作者：
Calis, Sema;Ozturk-Atar, Kivilcim;Capan, Yilmaz
通讯作者：
Capan, Yilmaz
影响因子：
14
作者：
Cheng, Jianjun;Teply, Benjamin A.;Farokhzad, Omid C.
通讯作者：
Farokhzad, Omid C.
影响因子：
4.6
作者：
Han TL;Sha H;Ji J;Li YT;Wu DS;Lin H;Hu B;Jiang ZX
通讯作者：
Jiang ZX
影响因子：
5
作者：
通讯作者：
--
影响因子：
3.1
作者：
Soomherun N;Kreua-Ongarjnukool N;Chumnanvej S;Thumsing S
通讯作者：
Thumsing S