Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, United States.
Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai, China.
J Control Release. 2016 Sep 10;237:168-76. doi: 10.1016/j.jconrel.2016.07.015. Epub 2016 Jul 11.
We have previously tested paclitaxel nanocrystals (PTX-NCs) in tumor murine models and learned that the nanocrystal formulation could achieve similar and superior anticancer efficacy to the conventional Taxol® formulation, but with significantly reduced side-effects. The nanocrystals were not coated with any surfactants and a majority of the injected dose was taken up by the liver (>40%), while a minimal amount was present in the blood circulation and quickly eliminated. The aim of this work was to treat the surface of PTX-NCs with PEG-based polymers and examine the impact by surface coating on biodistribution, pharmacokinetics, and tumor retention. Testing in tumor-bearing mice showed that PTX-NCs treated with Pluronic® F68 (PEG-PPG-PEG block polymer) significantly enhanced blood circulation of the drug and accumulation in tumor tissue. The absolute amount reaching the tumor, however, was still minimal relative to the dose.
我们之前曾在肿瘤鼠模型中测试紫杉醇纳米晶体（PTX-NCs），并了解到纳米晶体制剂可以达到与传统的 Taxol®制剂相似甚至更优的抗癌疗效，但副作用明显减少。这些纳米晶体没有用任何表面活性剂进行涂层，大部分注射剂量被肝脏吸收（>40%），而在血液循环中存在的量非常少且很快被清除。这项工作的目的是用基于 PEG 的聚合物对 PTX-NCs 的表面进行处理，并研究表面涂层对其分布、药代动力学和肿瘤滞留的影响。在荷瘤小鼠中的测试表明，用聚氧乙烯-聚氧丙烯-聚氧乙烯（PEG-PPG-PEG 嵌段聚合物）处理的 PTX-NCs 显著增强了药物的血液循环和在肿瘤组织中的积累。然而，到达肿瘤的绝对数量相对于剂量仍然很少。
