Contipro a.s., Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic; Department of Analytical Chemistry, Faculty of Science, Palacký University, 17. Listopadu 12, 771 46 Olomouc, Czech Republic.
Contipro a.s., Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
Carbohydr Polym. 2019 Apr 1;209:181-189. doi: 10.1016/j.carbpol.2018.12.104. Epub 2019 Jan 3.
A better understanding of in vivo behavior of nanocarriers is necessary for further improvement in their development. Here we present a novel approach, where both the matrix and the drug can be analyzed by LCMS/MS after one sample handling. The developed method was applied for the comparison of pharmacokinetic profile of free and encapsulated doxorubicin (DOX) in oleyl hyaluronan (HA-C18:1) polymeric micelles. The results indicated that nanocarriers were rapidly dissociated upon in vivo administration. Despite this fact, the administration of encapsulated DOX led to its longer circulation time and enhanced tumor targeting. This effect was not observed injecting blank HA-C18:1 micelles followed by unencapsulated DOX. Biodistribution studies and molecular weight estimation of the carrier matrix indicated relatively high stability of HA-C18:1 ester bond in bloodstream and complete elimination of the derivative within 72 h. The proposed methodology provides a novel strategy to elucidate the pharmacokinetic behavior of polysaccharide-based drug delivery systems.
为了进一步提高纳米载体的开发水平，有必要更好地了解其体内行为。在这里，我们提出了一种新方法，通过一次样品处理，即可对基质和药物进行 LCMS/MS 分析。该方法用于比较游离阿霉素（DOX）和包封 DOX 在油酰透明质酸（HA-C18:1）聚合物胶束中的药代动力学特征。结果表明，纳米载体在体内给药后迅速解离。尽管如此，包封 DOX 的给药导致其循环时间延长，并增强了肿瘤靶向性。而注射空白 HA-C18:1 胶束后再注射游离 DOX 则未观察到这种效果。载体基质的分布研究和分子量估计表明，HA-C18:1 酯键在血液中的稳定性相对较高，并且在 72 小时内完全消除了该衍生物。所提出的方法为阐明基于多糖的药物传递系统的药代动力学行为提供了一种新策略。
