Jing Jing, Tupally Karnaker R, Kokil Ganesh R, Qu Zhi, Chen Sibao, Parekh Harendra S
School of Pharmacy, The University of Queensland 20 Cornwall Street, Woolloongabba QLD 4012 Australia
State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute Shenzhen 518057 People's Republic of China
RSC Adv. 2019 Jan 18;9(5):2458-2463. doi: 10.1039/c8ra09606f.
The discovery that a cane toad poison-derived steroid, bufalin can significantly impact cancer cell proliferation supports its potential use in cancer therapy. However, its poor aqueous solubility and tissue deposition characteristics hamper its broader application as an anticancer therapeutic agent in its own right. To address this we developed an amphiphilic dendrimer-based delivery system, which self-assembles into discrete micelles in an aqueous environment. The bufalin-micelle inclusion complex was prepared by the co-precipitation method and their presence was confirmed by dynamic light scattering (DLS), zeta potential and differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) measurements. The self-assembled bufalin-containing micelles were found to form at/above the dendrimer concentration of 105.38 μmol L, and showed a more than threefold increase in the aqueous solubility (142.9 μg mL) of bufalin, when compared with a saturated bufalin aqueous solution (42.4 μg mL), and two non-assembling peptides of similar composition (79.3 and 62.5 μg mL respectively).
从甘蔗蟾蜍毒液中提取的类固醇物质蟾毒灵能够显著影响癌细胞增殖，这一发现支持了其在癌症治疗中的潜在应用价值。然而，其较差的水溶性和组织沉积特性阻碍了它自身作为一种抗癌治疗药物的广泛应用。为了解决这一问题，我们开发了一种基于两亲性树枝状聚合物的递送系统，该系统在水性环境中会自组装成离散的胶束。通过共沉淀法制备了蟾毒灵-胶束包合物，并通过动态光散射（DLS）、ζ电位、差示扫描量热法（DSC）和透射电子显微镜（TEM）测量证实了它们的存在。发现当树枝状聚合物浓度达到/高于105.38 μmol/L时会形成自组装的含蟾毒灵胶束，与饱和蟾毒灵水溶液（42.4 μg/mL）以及两种组成相似的非组装肽（分别为79.3和62.5 μg/mL）相比，蟾毒灵在胶束中的水溶性提高了三倍多（达到142.9 μg/mL）。
