Faculty of Pharmaceutical Sciences, Naresuan University, 99 Moo 9, Amphoe Muang, Phitsanulok, 65000, Thailand.
The Center of Excellence for Innovation in Chemistry (PERCH-CIC), Commission on Higher Education, Ministry of Education, Bangkok, Thailand.
Drug Deliv Transl Res. 2020 Apr;10(2):413-424. doi: 10.1007/s13346-019-00682-7.
Colon cancer is one of the most life-threatening cancers with high incidence and mortality rates. Current first-line treatments are ineffective and possess many unwanted effects. The off-label use of paclitaxel encapsulated in nanoparticles proves an innovative approach. In this study, we reported novel paclitaxel loaded EDC-crosslinked fibroin nanoparticles (PTX-FNPs) for anticancer purpose. The particles were formulated using desolvation method and the physicochemical properties were controlled favorably, including the particle size (300-500 nm), zeta potential (- 15 to + 30 mV), drug entrapment efficiency (75-100%), crystallinity, drug solubility (1- to 10-fold increase), dissolution profiles, stability (> 24 h in intravenous diluent and > 6 months storage at 4 °C). In in vitro study, all formulations showed no toxicity on the red blood cells, whereas retained the paclitaxel cytotoxicity on MCF-7 breast cancer and Caco-2 colon cancer cells. Interestingly, PTX-FNPs can be uptaken rapidly by the Caco-2 cells, consequently increased paclitaxel potency up to 10-fold compared to the free drug. Graphical abstract.
结肠癌是一种最具威胁生命的癌症之一,其发病率和死亡率都很高。目前的一线治疗方法效果不佳,且存在许多不良反应。紫杉醇纳米粒的超说明书使用证明是一种创新的方法。在本研究中,我们报道了一种新型的载紫杉醇的 EDC 交联丝素纳米粒(PTX-FNPs)用于抗癌目的。该纳米粒是通过去溶剂化方法制备的,并对其物理化学性质进行了有利的控制,包括粒径(300-500nm)、Zeta 电位(-15 至+30mV)、载药量(75-100%)、结晶度、药物溶解度(增加 1-10 倍)、溶解曲线、稳定性(静脉稀释液中>24h 和 4°C 下储存>6 个月)。在体外研究中,所有制剂对红细胞均无毒性,而对 MCF-7 乳腺癌和 Caco-2 结肠癌细胞保留了紫杉醇的细胞毒性。有趣的是,PTX-FNPs 可以被 Caco-2 细胞迅速摄取,因此与游离药物相比,紫杉醇的效力增加了 10 倍。