Department Pharmacy and Pharmaceutical Technology, University of Navarra, Pamplona, Spain.
Eur J Pharm Biopharm. 2012 Aug;81(3):514-23. doi: 10.1016/j.ejpb.2012.04.001. Epub 2012 Apr 10.
The aim of this work was to study the potential of pegylated poly(anhydride) nanoparticles as carriers for the oral delivery of paclitaxel (PTX). Paclitaxel is an anticancer drug, ascribed to the class IV of the Biopharmaceutical Classification system, characterised for its low aqueous solubility and to act as a substrate of the P-glycoprotein and cytochrome P450. For the pegylation of nanoparticles, three different poly(ethylene glycol) (PEG) were used: PEG 2000 (PTX-NP2), PEG 6000 (PTX-NP6) and PEG 10,000 (PTX-NP10). The transport and permeability of paclitaxel through the jejunum mucosa of rats was determined in Ussing chambers, whereas its oral bioavailability was studied in rats. The loading of PTX in pegylated nanoparticles increased between 3 and 7 times the intestinal permeability of paclitaxel through the jejunum compared with the commercial formulation Taxol. Interestingly, the permeability of PTX was significantly higher for PTX-NP2 and PTX-NP6 than for PTX-NP10. In the in vivo studies, similar results were obtained. When PTX-NP2 and PTX-NP6 were administered to rats by the oral route, sustained and therapeutic plasma levels of paclitaxel for at least 48 h were observed. The relative oral bioavailability of paclitaxel delivered in nanoparticles was calculated to be 70% for PTX-NP2, 40% for PTX-NP6 and 16% in case of PTX-NP10. All of these observations would be related with both the bioadhesive properties of these carriers and the inhibitory effect of PEG on the activity of both P-gp and P450 cytochrome.
本工作旨在研究聚乙二醇化聚（酸酐）纳米粒作为紫杉醇（PTX）口服给药载体的潜力。紫杉醇是一种抗癌药物，属于生物制药分类系统的第四类，其特点是水溶性低，并作为 P-糖蛋白和细胞色素 P450 的底物。为了对纳米粒进行聚乙二醇化，使用了三种不同的聚乙二醇（PEG）：PEG 2000（PTX-NP2）、PEG 6000（PTX-NP6）和 PEG 10,000（PTX-NP10）。在 Ussing 室中测定了紫杉醇通过大鼠空肠黏膜的转运和渗透，在大鼠中研究了其口服生物利用度。与商业制剂 Taxol 相比，PTX 负载在聚乙二醇化纳米粒中的量使紫杉醇通过空肠的肠道渗透增加了 3 至 7 倍。有趣的是，PTX-NP2 和 PTX-NP6 的渗透明显高于 PTX-NP10。在体内研究中也得到了类似的结果。当 PTX-NP2 和 PTX-NP6 通过口服途径给予大鼠时，至少观察到 48 小时的持续和治疗性紫杉醇血浆水平。纳米粒中紫杉醇的相对口服生物利用度计算为 PTX-NP2 为 70%，PTX-NP6 为 40%，PTX-NP10 为 16%。所有这些观察结果都与这些载体的生物黏附特性以及 PEG 对 P-糖蛋白和细胞色素 P450 的活性的抑制作用有关。
