Understanding the structure and stability of paclitaxel nanocrystals.
Understanding the structure and stability of paclitaxel nanocrystals.
复制标题
DOI：
10.1016/j.ijpharm.2010.02.013
复制
发表时间：
2010-05-10
影响因子：
5.8
通讯作者：
Liu, Feng
中科院分区：
文献类型：
--
作者：
Deng, Jiexin;Huang, Leaf;Liu, Feng
以前，PTX/Pluronic F127纳米晶体是在我们的实验室中使用纳米晶体稳定化（SNC）方法制备的。对于PTX纳米晶体，可以增加剂量以产生优于Taxol®的改善的抗肿瘤活性，而不发生急性毒性。本研究的目的是进一步了解PTX纳米晶体的结构和稳定性。在制剂中加入更多的Pluronic F127表面活性剂，以试图进一步稳定纳米晶体，防止热诱导的聚集。然而，这导致胶束的形成，使纳米晶体的稳定性恶化。F127脱附实验表明，在CMC以下和CMC以上，表面活性剂对表面活性剂的吸附亲和力不同。低于CMC的单体以高亲和力结合到表面活性剂表面，但高于CMC的低亲和力表面活性剂聚集体在稀释时容易离开表面。在较高温度下，由于CMC显著降低，F127胶束化的趋势增强。因此，在37 °C下，即使对于用低量的F127（1/5 w/w PTX/F127）制备的纳米晶体，也存在F127解吸。为了提高纳米晶体的稳定性，使用通过孵育-超声处理程序的再纳米化来破坏PTX的优选晶体生长模式。此外，我们已经证明，在孵育-超声处理程序中使用的更高的加热温度（45 °C对37 °C）能够在长时间孵育期间提供甚至更好的热稳定性。
Previously, PTX/Pluronic F127 nanocrystals were prepared in our laboratory using the Stabilization of Nanocrystals (SNC) method. For PTX nanocrystals, dosages could be increased to yield improved antitumor activity over Taxol® without incidence of acute toxicity. The objectives of this current study are to further understand the structure and stability of PTX nanocrystals. More Pluronic F127 surfactant was added in the formulation to attempt to further stabilize the nanocrystals against thermal induced aggregation. However, this resulted in formation of micelles that worsened the stability of nanocrystals. The F127 desorption experiment suggested different surfactant adsorption affinity to nanocrystal surface below and above the CMC. Below the CMC monomers bound to nanocrystal surface with high affinity, but above the CMC low affinity surfactant aggregates readily left the surface upon dilution. At higher temperature the tendency of F127 micellization is enhanced due to drastically lower CMC. Consequently, at 37 °C there was F127 desorption even for nanocrystals prepared with low amounts of F127 (1/5 w/w PTX/F127). To improve the stability of nanocrystals, re-nanonization by Incubation-Sonication procedure was used to disrupt the preferred crystal growth pattern of PTX. Furthermore, we have demonstrated that a higher heating temperature (45 °C vs. 37 °C) used in the Incubation-Sonication procedure was able to provide even better nanocrystal stability for long periods of incubation time.
登录
查看更多内容
影响因子：
10.8
作者：
Croy, SR;Kwon, GS
通讯作者：
Kwon, GS
影响因子：
5.8
作者：
Kocbek, P;Baumgartner, S;Kristl, J
通讯作者：
Kristl, J
影响因子：
3.3
作者：
Lin, YN;Alexandridis, P
通讯作者：
Alexandridis, P
影响因子：
5.5
作者：
LINSE, P;MALMSTEN, M
通讯作者：
MALMSTEN, M
影响因子：
10.8
作者：
Kim, SC;Kim, DW;Seo, MH
通讯作者：
Seo, MH