Direct comparison of two albumin-based paclitaxel-loaded nanoparticle formulations: Is the crosslinked version more advantageous?
Direct comparison of two albumin-based paclitaxel-loaded nanoparticle formulations: Is the crosslinked version more advantageous?
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DOI：
10.1016/j.ijpharm.2014.04.010
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发表时间：
2014-07-01
影响因子：
5.8
通讯作者：
Cui, Jingxia
中科院分区：
文献类型：
--
作者：
Li, Chunlei;Li, Yanhui;Cui, Jingxia
以白蛋白为载体的纳米粒已成为药物传递的主流。据报道，未交联白蛋白纳米粒在循环中不稳定，可以通过gp60/SPARC途径将药物输送到肿瘤中；相比之下，具有稳定纳米粒的药物输送依赖于增强的通透性和滞留效应。因此，哪种纳米颗粒更具优势是值得商榷的。制备了两种不同版本的白蛋白结合紫杉醇纳米粒。在体外，未交联物能迅速崩解，交联物稳定。两种剂型的药代动力学不同，尤其是在早期，非交联型微粒被迅速清除。紫杉醇经非交联型微粒治疗后有向心、肾蓄积的趋势，经交联型微粒治疗后更易进入肺、脾、肝等脏器。紫杉醇在非交联型微粒治疗后对肿瘤的转运效率高于交联型紫杉醇(p<；0.05)，从而显著提高了抗肿瘤活性。此外，非交联剂的毒性只略高一点。结果表明，非交联型制剂更有利于紫杉醇的释放，我们的结论可推广到白蛋白纳米粒给药的其他亲脂性药物。(C)2014爱思唯尔B.V.保留所有权利。
Nanoparticles using albumin as particle matrix have entered the mainstream of drug delivery. It was reported that non-crosslinked albumin nanoparticles were unstable in circulation and could deliver drugs into tumor through gp60/SPARC pathway; in contrast, the delivery of drugs with stable nanoparticles was dependent on enhanced permeability and retention effect. Thus, it is questionable which kind of nanoparticles was more advantageous. Two versions of albumin-bound paclitaxel nanoparticles were prepared. In vitro, the non-crosslinked particles could rapidly disintegrate and the crosslinked was stable. The pharmacokinetics of both formulations was different especially at early time and the non-crosslinked particles were cleared rapidly. After non-crosslinked particle treatment paclitaxel had a tendency to accumulate into heart and kidney and following therapy with the crosslinked particles, paclitaxel was liable to be delivered into lung, spleen and liver. The delivery efficiency of paclitaxel into tumor following the non-crosslinked particle treatment was greater than that of the crosslinked (p < 0.05), thus resulting in a considerably improved antineoplastic activity. Moreover, the non-crosslinked formulation was only slightly more toxic. It was concluded that the non-crosslinked formulation was more advantageous for the delivery of paclitaxel and our conclusion might be generalized to other lipophilic drugs delivered with albumin nanoparticles. (C) 2014 Elsevier B. V. All rights reserved.