College of Pharmacy, Ajou University, Suwon 16499, Republic of Korea; Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, Canada.
College of Pharmacy, Ajou University, Suwon 16499, Republic of Korea.
Eur J Pharm Biopharm. 2020 Jul;152:257-269. doi: 10.1016/j.ejpb.2020.05.011. Epub 2020 May 16.
This study aimed to design the ideal nanonizing vehicle for poorly water-soluble model curcumin (CCM) using fattigation-platform nanotechnology, and to investigate the effects of fatty acid salts chain length on nanonizing CCM and its efficient delivery to different cancer cells. HSA-fatty acid conjugates were synthesized by EDC/NHS coupling. Fattigation-platform nanomicelles (NMs), prepared by film hydration, exhibited uniform and spherical morphology, although, each NM varied in particle size, zeta potential, and critical micelle concentration according to the types of fatty acid. Preliminary solubility studies of albumin conjugates with 5 types of fatty acid salts of different chain lengths revealed that C14 exhibited the highest solubilization of CCM. CCM-loaded HSA-C14 NMs demonstrated the highest drug content (5.35 ± 0.48%) and loading efficiency (95.93 ± 1.87%) compared to other NMs. It exhibited enhanced drug release rate and reduced micelle size in biorelevant dissolution medium. Interestingly, this solubilization approach was well applied in poorly water-soluble docetaxel trihydrate (DTX). Preliminary solubility results of DTX was also corresponded to the stable nanonization phenomenon in biorelevant dissolution medium. Compared to the CCM EtOH solution, HSA-C14 NMs showed higher internalization in cancer cell lines A549 and MCF-7, and consequently, exhibited significantly increased cytotoxicity against both cell lines. Therefore, this study provides a new solubilization approach for poorly water-soluble drugs using fatty acid salts of different chain lengths and their micellar formations via nanonization, which could be a promising tool for targeted cancer therapy using poorly water-soluble drugs.
本研究旨在利用疲劳平台纳米技术设计出理想的用于难溶性模型姜黄素（CCM）的纳米化载体，并研究脂肪酸盐链长对纳米化 CCM 及其向不同癌细胞高效传递的影响。通过 EDC/NHS 偶联合成 HSA-脂肪酸缀合物。薄膜水化法制备的疲劳平台纳米胶束（NMs）表现出均匀的球形形态，但由于脂肪酸的类型不同，每个 NM 的粒径、Zeta 电位和临界胶束浓度均有所不同。对具有 5 种不同链长脂肪酸盐的白蛋白缀合物的初步溶解度研究表明，C14 对 CCM 的溶解度最高。与其他 NMs 相比，载有 CCM 的 HSA-C14 NM 表现出最高的药物含量（5.35±0.48%）和载药效率（95.93±1.87%）。它在生物相关溶解介质中表现出更高的药物释放速率和更小的胶束尺寸。有趣的是，这种增溶方法在难溶性多西他赛三水合物（DTX）中也得到了很好的应用。DTX 的初步溶解度结果也与生物相关溶解介质中的稳定纳米化现象相对应。与 CCM EtOH 溶液相比，HSA-C14 NM 在 A549 和 MCF-7 癌细胞系中的内化程度更高，因此对这两种细胞系的细胞毒性显著增强。因此，本研究为使用不同链长的脂肪酸盐及其胶束形成通过纳米化对难溶性药物提供了一种新的增溶方法，这可能是使用难溶性药物进行靶向癌症治疗的有前途的工具。
