Ye Lei, Zhang Yabin, Yang Boguang, Zhou Xin, Li Junjie, Qin Zhihui, Dong Dianyu, Cui Yuanlu, Yao Fanglian
School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, China.
Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine , Tianjin 300193, China.
ACS Appl Mater Interfaces. 2016 Feb;8(7):4385-98. doi: 10.1021/acsami.5b10811. Epub 2016 Feb 15.
Over the last few decades, nanoparticles have been emerging as useful means to improve the therapeutic efficacy of drug delivery and medical diagnoses. However, the heterogeneity and complexity of blood as a medium is a fundamental problem; large amounts of protein can be adsorbed onto the surface of nanoparticles and cause their rapid clearance before reaching their target sites, resulting in the failure of drug delivery. To overcome this challenge, we present a rationally designed starch derivative (SB-ST-OC) with both a superhydrophilic moiety of zwitterionic sulfobetaine (SB) and a hydrophobic segment of octane (OC) as functional groups, which can self-assemble into "stealth" micelles (SSO micelles). The superhydrophilic SB kept the micelles stable against aggregation in complex media and imbued them with "stealth" properties, eventually extending their circulation time in blood. In stability and hemolysis tests the SSO micelles showed excellent protein resistance properties and hemocompatibility. Moreover, a phagocytosis test and cytokine secretion assay confirmed that the SSO micelles had less potential to trigger the activation of macrophages and were more suitable as a drug delivery candidate in vivo. On the basis of these results, doxorubicin (DOX), a hydrophobic drug, was used to investigate the potential application of this novel starch derivative in vivo. The results of the pharmacokinetic study showed that the values of the plasma area under the concentration curve (AUC) and elimination half-life (T1/2) of the SSO micelles were higher than those of micelles without SB modifications. In conclusion, the combination of excellent protein resistance, lower macrophage activation, and longer circulation time in vivo makes this synthesized novel starch derivative a promising candidate as a hydrophobic drug carrier for long-term circulation in vivo.
在过去几十年中，纳米颗粒已成为提高药物递送治疗效果和医学诊断的有用手段。然而，血液作为一种介质的异质性和复杂性是一个基本问题；大量蛋白质可吸附在纳米颗粒表面，导致它们在到达靶位点之前就被快速清除，从而导致药物递送失败。为了克服这一挑战，我们提出了一种合理设计的淀粉衍生物（SB-ST-OC），其具有两性离子磺基甜菜碱（SB）的超亲水部分和辛烷（OC）的疏水部分作为官能团，它可以自组装成“隐形”胶束（SSO胶束）。超亲水的SB使胶束在复杂介质中保持稳定，防止聚集，并赋予它们“隐形”特性，最终延长它们在血液中的循环时间。在稳定性和溶血试验中，SSO胶束表现出优异的抗蛋白质性能和血液相容性。此外，吞噬试验和细胞因子分泌测定证实，SSO胶束触发巨噬细胞活化的潜力较小，更适合作为体内药物递送候选物。基于这些结果，使用疏水性药物阿霉素（DOX）来研究这种新型淀粉衍生物在体内的潜在应用。药代动力学研究结果表明，SSO胶束的血浆浓度曲线下面积（AUC）和消除半衰期（T1/2）值高于未进行SB修饰的胶束。总之，优异的抗蛋白质性能、较低的巨噬细胞活化以及在体内更长的循环时间相结合，使得这种合成的新型淀粉衍生物成为一种有前途的候选物，可作为疏水性药物载体在体内进行长期循环。
