Maniam Geetha, Mai Chun-Wai, Zulkefeli Mohd, Dufès Christine, Tan Doryn Meam-Yee, Fu Ju-Yen
School of Postgraduate Studies, International Medical University, Bukit Jalil, Malaysia.
Product Development and Advisory Services Division, Malaysian Palm Oil Board, Bandar Baru Bangi, Malaysia.
Front Pharmacol. 2018 Nov 26;9:1358. doi: 10.3389/fphar.2018.01358. eCollection 2018.
Plant-derived phytonutrients have emerged as health enhancers. Tocotrienols from the vitamin E family gained high attention in recent years due to their multi-targeted biological properties, including lipid-lowering, neuroprotection, anti-inflammatory, antioxidant, and anticancer effects. Despite well-defined mechanism of action as an anti-cancer agent, their clinical use is hampered by poor pharmacokinetic profile and low oral bioavailability. Delivery systems based on nanotechnology were proven to be advantageous in elevating the delivery of tocotrienols to tumor sites for enhanced efficacy. To date, preclinical development of nanocarriers for tocotrienols include niosomes, lipid nanoemulsions, nanostructured lipid carriers (NLCs) and polymeric nanoparticles. Active targeting was explored via the use of transferrin as targeting ligand in niosomes. , nanocarriers were shown to enhance the anti-proliferative efficacy and cellular uptake of tocotrienols in cancer cells. , improved bioavailability of tocotrienols were reported with NLCs while marked tumor regression was observed with transferrin-targeted niosomes. In this review, the advantages and limitations of each nanocarriers were critically analyzed. Furthermore, a number of key challenges were identified including scale-up production, biological barriers, and toxicity profiles. To overcome these challenges, three research opportunities were highlighted based on rapid advancements in the field of nanomedicine. This review aims to provide a wholesome perspective for tocotrienol nanoformulations in cancer therapy directed toward effective clinical translation.
植物源植物营养素已成为健康促进剂。近年来，维生素E家族的生育三烯酚因其多靶点生物学特性而备受关注，这些特性包括降脂、神经保护、抗炎、抗氧化和抗癌作用。尽管其作为抗癌剂的作用机制已明确，但它们的临床应用受到不良药代动力学特征和低口服生物利用度的阻碍。基于纳米技术的递送系统已被证明在提高生育三烯酚向肿瘤部位的递送以增强疗效方面具有优势。迄今为止，生育三烯酚纳米载体的临床前开发包括非离子型表面活性剂囊泡、脂质纳米乳剂、纳米结构脂质载体（NLCs）和聚合物纳米颗粒。通过在非离子型表面活性剂囊泡中使用转铁蛋白作为靶向配体来探索主动靶向。结果表明，纳米载体可增强生育三烯酚在癌细胞中的抗增殖功效和细胞摄取。此外，据报道纳米结构脂质载体可提高生育三烯酚的生物利用度，而转铁蛋白靶向的非离子型表面活性剂囊泡则观察到明显的肿瘤消退。在本综述中，对每种纳米载体的优缺点进行了批判性分析。此外，还确定了一些关键挑战，包括扩大生产规模、生物屏障和毒性特征。为了克服这些挑战，基于纳米医学领域的快速进展突出了三个研究机会。本综述旨在为生育三烯酚纳米制剂在癌症治疗中的有效临床转化提供一个全面的视角。
