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首页> 外文期刊>International Journal of Nanomedicine >Preparation, in vitro and in vivo evaluation of polymeric nanoparticles based on hyaluronic acid-poly(butyl cyanoacrylate) and D-alpha-tocopheryl polyethylene glycol 1000 succinate for tumor-targeted delivery of morin hydrate
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Preparation, in vitro and in vivo evaluation of polymeric nanoparticles based on hyaluronic acid-poly(butyl cyanoacrylate) and D-alpha-tocopheryl polyethylene glycol 1000 succinate for tumor-targeted delivery of morin hydrate

机译：基于透明质酸-聚（氰基丙烯酸丁酯）和D-α-生育酚聚乙二醇1000琥珀酸酯的聚合物纳米粒的制备，体外和体内评价，用于靶向性投递morin水合物

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Abstract: Herein, we describe the preparation of a targeted cellular delivery system for morin hydrate (MH), based on a low-molecular-weight hyaluronic acid-poly(butyl cyanoacrylate) (HA-PBCA) block copolymer. In order to enhance the therapeutic effect of MH, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was mixed with HA-PBCA during the preparation process. The MH-loaded HA-PBCA “plain” nanoparticle (MH-PNs) and HA-PBCA/TPGS “mixed” nanoparticles (MH-MNs) were concomitantly characterized in terms of loading efficiency, particle size, zeta potential, critical aggregation concentration, and morphology. The obtained MH-PNs and MH-MNs exhibited a spherical morphology with a negative zeta potential and a particle size less than 200 nm, favorable for drug targeting. Remarkably, the addition of TPGS resulted in about 1.6-fold increase in drug-loading. The in vitro cell viability experiment revealed that MH-MNs enhanced the cytotoxicity of MH in A549 cells compared with MH solution and MH-PNs. Furthermore, blank MNs containing TPGS exhibited selective cytotoxic effects against cancer cells without diminishing the viability of normal cells. In addition, the cellular uptake study indicated that MNs resulted in 2.28-fold higher cellular uptake than that of PNs, in A549 cells. The CD44 receptor competitive inhibition and the internalization pathway studies suggested that the internalization mechanism of the nanoparticles was mediated mainly by the CD44 receptors through a clathrin-dependent endocytic pathway. More importantly, MH-MNs exhibited a higher in vivo antitumor potency and induced more tumor cell apoptosis than did MH-PNs, following intravenous administration to S180 tumor-bearing mice. Overall, the results imply that the developed nanoparticles are promising vehicles for the targeted delivery of lipophilic anticancer drugs.
机译：摘要：本文中，我们描述了一种基于低分子量透明质酸-聚（氰基丙烯酸丁酯）（HA-PBCA）嵌段共聚物的水合莫林（MH）靶向细胞递送系统的制备。为了提高MH的治疗效果，在制备过程中将D-α-生育酚聚乙二醇1000琥珀酸酯（TPGS）与HA-PBCA混合。 MH负载的HA-PBCA“纯”纳米粒子（MH-PNs）和HA-PBCA / TPGS“混合”的纳米粒子（MH-MN）的负载效率，粒度，ζ电势，临界聚集浓度，和形态。所获得的MH-PNs和MH-MNs显示出具有负ζ电势且粒径小于200nm的球形形态，有利于药物靶向。值得注意的是，TPGS的添加导致载药量增加了约1.6倍。体外细胞活力实验表明，与MH溶液和MH-PNs相比，MH-MNs增强了A549细胞中MH的细胞毒性。此外，含有TPGS的空白MN对癌细胞具有选择性的细胞毒性作用，而不会降低正常细胞的活力。此外，细胞摄取研究表明，在A549细胞中，MNs引起的细胞摄取比PNs高2.28倍。 CD44受体竞争抑制和内在化途径研究表明，纳米粒子的内在化机理主要是通过网格蛋白依赖性内吞途径由CD44受体介导的。更重要的是，在对S180荷瘤小鼠静脉内给药后，MH-MNs比MH-PNs表现出更高的体内抗肿瘤能力并诱导更多的肿瘤细胞凋亡。总体而言，该结果表明，所开发的纳米颗粒是用于靶向递送亲脂性抗癌药物的有希望的载体。

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