Ngema Lindokuhle M, Acter Shahinur, Adeyemi Samson A, Marimuthu Thashree, Govender Mershen, Ngwa Wilfred, Choonara Yahya E
Wits Advanced Drug Delivery Platform, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa.
Sidney Kimmel Comprehensive Cancer Center, Department of Radiation Oncology & Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD 21218, USA.
Pharmaceutics. 2024 Dec 1;16(12):1536. doi: 10.3390/pharmaceutics16121536.
The effectiveness of paclitaxel (PTX) in treating non-small-cell lung carcinoma (NSCLC) is restricted by its poor pharmacokinetic profile and side effects. This limitation stems from the lack of a suitable delivery vector to efficiently target cancer cells. Therefore, there is a critical need to develop an efficient carrier for the optimised delivery of PTX in NSCLC therapy. The present study describes the fabrication of mesoporous polydopamine (mPDA) nano-bowls via an emulsion-induced interfacial anisotropic assembly method, designed for efficient entrapment of PTX and pH-responsive release behaviour. The nano-bowls depicted a typical bowl-like shape, with connecting mesoporous channels and a central hollow cavity, allowing optimal loading of PTX. The fabricated nanocarrier system, mPDA-PTX-nb, had a mean hydrodynamic bowl diameter of 200.4 ± 5.2 nm and a surface charge of -39.2 ± 1.3 mV. The entrapment efficiency of PTX within the nano-bowls was found to be 95.7%, with a corresponding release of 85.1% achieved at the acidic pH 5.9 (simulated tumour microenvironment) at 48 h. Drug release was best fitted to the Peppas-Sahlin model, indicating the involvement of both diffusion and relaxation mechanisms. Treatment with mPDA-PTX-nb significantly suppressed A549 lung cancer cell proliferation at 48 and 72 h, resulting in cell viability of 14.0% and 9.3%, respectively, at the highest concentration (100 µg/mL). These results highlight the potential of mPDA-PTX-nb as an effective nanocarrier for PTX, promoting enhanced anti-proliferative effects in NSCLC therapy.
紫杉醇(PTX)治疗非小细胞肺癌(NSCLC)的有效性受到其不良药代动力学特征和副作用的限制。这种局限性源于缺乏合适的递送载体来有效靶向癌细胞。因此,迫切需要开发一种高效载体,用于在NSCLC治疗中优化PTX的递送。本研究描述了通过乳液诱导界面各向异性组装方法制备介孔聚多巴胺(mPDA)纳米碗,其设计用于有效包封PTX并具有pH响应释放行为。纳米碗呈现出典型的碗状形状,具有连接的介孔通道和中央中空腔,可实现PTX的最佳负载。制备的纳米载体系统mPDA-PTX-nb的平均流体动力学碗直径为200.4±5.2 nm,表面电荷为-39.2±1.3 mV。发现PTX在纳米碗中的包封率为95.7%,在48小时时,在酸性pH 5.9(模拟肿瘤微环境)下相应释放率达到85.1%。药物释放最符合Peppas-Sahlin模型,表明涉及扩散和松弛机制。用mPDA-PTX-nb处理在48小时和72小时时显著抑制A549肺癌细胞增殖,在最高浓度(100 µg/mL)下,细胞活力分别为14.0%和9.3%。这些结果突出了mPDA-PTX-nb作为PTX有效纳米载体的潜力,在NSCLC治疗中促进增强的抗增殖作用。