Lomis Nikita, Westfall Susan, Farahdel Leila, Malhotra Meenakshi, Shum-Tim Dominique, Prakash Satya
Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, 3775 University Street, Montreal, QC H3A 2B4, Canada.
Division of Experimental Medicine, 1110 Pins Avenue, Montreal, QC H3A 1A3, Canada.
Nanomaterials (Basel). 2016 Jun 15;6(6):116. doi: 10.3390/nano6060116.
Human serum albumin nanoparticles (HSA-NPs) are widely-used drug delivery systems with applications in various diseases, like cancer. For intravenous administration of HSA-NPs, the particle size, surface charge, drug loading and release kinetics are important parameters for consideration. This study focuses on the development of stable HSA-NPs containing the anti-cancer drug paclitaxel (PTX) via the emulsion-solvent evaporation method using a high-pressure homogenizer. The key parameters for the preparation of PTX-HSA-NPs are: the starting concentrations of HSA, PTX and the organic solvent, including the homogenization pressure and its number cycles, were optimized. Results indicate a size of 143.4 ± 0.7 nm and 170.2 ± 1.4 nm with a surface charge of -5.6 ± 0.8 mV and -17.4 ± 0.5 mV for HSA-NPs and PTX-HSA-NPs (0.5 mg/mL of PTX), respectively. The yield of the PTX-HSA-NPs was ~93% with an encapsulation efficiency of ~82%. To investigate the safety and effectiveness of the PTX-HSA-NPs, an drug release and cytotoxicity assay was performed on human breast cancer cell line (MCF-7). The PTX-HSA-NPs showed dose-dependent toxicity on cells of 52%, 39.3% and 22.6% with increasing concentrations of PTX at 8, 20.2 and 31.4 μg/mL, respectively. In summary, all parameters involved in HSA-NPs' preparation, its anticancer efficacy and scale-up are outlined in this research article.
人血清白蛋白纳米粒（HSA-NPs）是广泛应用的药物递送系统，可用于治疗包括癌症在内的各种疾病。对于HSA-NPs的静脉给药，粒径、表面电荷、药物负载量和释放动力学是需要考虑的重要参数。本研究聚焦于通过使用高压均质机的乳液-溶剂蒸发法开发含有抗癌药物紫杉醇（PTX）的稳定HSA-NPs。制备PTX-HSA-NPs的关键参数包括：HSA、PTX和有机溶剂的起始浓度，以及均质压力及其循环次数，均进行了优化。结果表明，HSA-NPs和PTX-HSA-NPs（0.5 mg/mL PTX）的粒径分别为143.4±0.7 nm和170.2±1.4 nm，表面电荷分别为-5.6±0.8 mV和-17.4±0.5 mV。PTX-HSA-NPs的产率约为93%，包封率约为82%。为了研究PTX-HSA-NPs的安全性和有效性，对人乳腺癌细胞系（MCF-7）进行了药物释放和细胞毒性测定。随着PTX浓度分别增加到8、20.2和31.4 μg/mL，PTX-HSA-NPs对细胞显示出剂量依赖性毒性，毒性分别为52%、39.3%和22.6%。总之，本研究文章概述了HSA-NPs制备过程中涉及的所有参数、其抗癌功效及放大生产情况。
