Product Development Cell, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Product Development Cell, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Int J Biol Macromol. 2019 Jul 15;133:495-502. doi: 10.1016/j.ijbiomac.2019.04.124. Epub 2019 Apr 17.
In recent years, a great deal of attention has been given towards re-purposing and re-innovating the potential drugs. In this regard, dihydroartemisinin (DHA) has been reported to demonstrate anti-proliferative effects on various cancerous cells viz. breast, liver and lung. However, it is associated with some limitations, such as low bioavailability which is hampered by its poor aqueous solubility and its rapid metabolism in systemic circulation. Therefore, in order to overcome these limitations, we synthesized a novel hyaluronic acid-dihydroartemisinin conjugate in which the hydroxyl group of DHA was covalently linked to carboxylic group of hyaluronic acid (HA). The conjugate was successfully characterized using H NMR, Fourier transform infrared spectroscopy (FT-IR) and gel permeation chromatography (GPC). The synthesized conjugate self-assembled into nanoparticles in aqueous solution. The developed nanoparticles were characterized for their average size, zeta potential, Transmission Electron Microscopy (TEM), X-ray Powder Diffraction (XRD) and loading efficiency. The nanoparticles were cytotoxic to lung cancer (A549) cell line which was determined using CCK-8 cell viability assay. This was further supported by Annexin-V-FITC-Propidium iodide apoptosis assay, reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) loss. Conclusively, present findings demonstrate hyaluronic acid conjugates can be used to improve the therapeutic outcomes of anticancer drugs.
近年来，人们对重新利用和创新潜在药物给予了极大的关注。在这方面，二氢青蒿素（DHA）已被报道对各种癌细胞（如乳腺癌、肝癌和肺癌）具有抗增殖作用。然而，它存在一些局限性，如生物利用度低，这是由于其在水中的溶解度低和在全身循环中的快速代谢所导致的。因此，为了克服这些局限性，我们合成了一种新型的透明质酸-二氢青蒿素缀合物，其中 DHA 的羟基与透明质酸（HA）的羧基共价连接。该缀合物成功地使用 H NMR、傅里叶变换红外光谱（FT-IR）和凝胶渗透色谱（GPC）进行了表征。该缀合物在水溶液中自组装成纳米粒子。所开发的纳米粒子的平均粒径、Zeta 电位、透射电子显微镜（TEM）、X 射线粉末衍射（XRD）和载药效率进行了表征。使用 CCK-8 细胞活力测定法，纳米粒子对肺癌（A549）细胞系具有细胞毒性。这进一步得到了 Annexin-V-FITC-Propidium iodide 凋亡测定、活性氧（ROS）产生和线粒体膜电位（MMP）丧失的支持。总之，目前的研究结果表明，透明质酸缀合物可用于提高抗癌药物的治疗效果。
