Preparation and in vitro anticancer activity of wheat germ agglutinin (WGA)-conjugated PLGA nanoparticles loaded with paclitaxel and isopropyl myristate
Preparation and in vitro anticancer activity of wheat germ agglutinin (WGA)-conjugated PLGA nanoparticles loaded with paclitaxel and isopropyl myristate
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DOI：
10.1016/j.jconrel.2004.06.024
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发表时间：
2005-09-20
影响因子：
10.8
通讯作者：
Lim, LY
中科院分区：
文献类型：
--
作者：
Mo, Y;Lim, LY
本研究的目的是开发一种新的凝集素共轭肉豆蔻酸异丙酯（IPM）的PLGA纳米粒子系统（NP）的局部输送紫杉醇到肺部。在对伴刀豆球蛋白A、蓖麻-120和WGA在A549、H1299和CCL-186细胞上的摄取进行比较研究之后，通过两步碳二亚胺法将纯胚芽凝集素（WGA）缀合到预先形成的负载IPM和紫杉醇的PLGA NP上。制备的WIT-NP平均直径为331 rim，zeta电位为-4.3mV，产率为66%，紫杉醇包封率为61%。通过与WGA的表面缀合来扩大粒径，而通过添加IPM和WGA来降低zeta电位。紫杉醇的体外释放曲线不受WGA的影响，但在制剂中添加IPM可增强初始药物释放。WIT-NP在前5小时内显示出约32%的紫杉醇载量的爆发释放，随后在接下来的115小时内显示出另外7%的药物载量的缓慢零级释放。与临床紫杉醇制剂、不含IPM或WGA的紫杉醇纳米粒或仅含IPM或WGA的紫杉醇纳米粒相比，WIT-NP对A549和H1299细胞具有上级体外细胞毒性。与A549细胞孵育5和24小时后，WIT-NP的IC 50无显著差异（分别为15.5和15 μ M），而临床制剂在5小时后无细胞毒性，但在24小时孵育后的IC 50为14 μ M。WIT-NP具有更强的细胞杀伤作用，因为WGA受体介导的细胞内吞作用和IPM促进的紫杉醇从NP中释放更有效的细胞摄取。(c)2005 Elsevier B. V.保留所有权利。
The purpose of this study was to develop a novel lectin-conjugated isopropyl myristate (IPM)-incorporated PLGA nanoparticle system (NP) for the local delivery of paclitaxel to the lungs. neat germ agglutinin (WGA) was conjugated onto preformed IPM- and paclitaxel-loaded PLGA NPs by a two-step carbodiimide method following comparative uptake studies of Concanavalin A, Ricinus communis-120 and WGA on A549, H1299 and CCL-186 cells. WIT-NP with mean diameter of 33 1 rim and zeta potential of -4.3 mV were prepared with yield of 66% and paclitaxel encapsulation efficiency of 61%. Particle size was expanded by surface conjugation with WGA, while zeta potential was reduced by the addition of IPM and WGA. In vitro paclitaxel release profile was not affected by WGA but initial drug release was enhanced by adding IPM into the formulation. The WIT-NP showed a burst-release of about 32% of the paclitaxel load within the first 5 h followed by a slow zero-order release of another 7% of the drug load in the next 115 h. Compared with the clinical paclitaxel formulation, paclitaxel-loaded nanoparticles without IPM or WGA, or paclitaxel-loaded nanoparticles with only IPM or WGA, the WIT-NP had superior in vitro cytotoxicity against A549 and H 1299 cells. IC50 for WIT-NP after 5 and 24 h incubation with A549 cells were not significantly different (15.5 and 15 mu M, respectively) whereas the clinical formulation was not cytotoxic after 5 h but had IC50 of 14 mu M after 24 h incubation. WIT-NP exhibited stronger cell-killing effect because of more efficient cellular uptake via WGA-receptor-mediated endocytosis and IPM-facilitated release of paclitaxel from the NPs. (c) 2005 Elsevier B.V. All rights reserved.