Preparation, cellular transport, and activity of polyamidoamine-based dendritic nanodevices with a high drug payload
Preparation, cellular transport, and activity of polyamidoamine-based dendritic nanodevices with a high drug payload
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DOI：
10.1016/j.biomaterials.2005.06.007
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发表时间：
2006-02-01
期刊：
影响因子：
14
通讯作者：
Kannan, RM
中科院分区：
文献类型：
--
作者：
Kolhe, P;Khandare, J;Kannan, RM
树枝状聚合物是一类新兴的高分子生物材料，在药物输送和成像方面具有应用。在树枝状大分子中实现高的药物负载，以及了解树枝状大分子-药物缀合物的治疗效果正受到越来越多的关注。通过布洛芬与聚酰胺胺（PAMAM-G4-OH）树枝状聚合物的共价缀合获得高药物有效载荷纳米器件。使用DCC作为偶联剂，将58个布洛芬分子共价缀合至第4代PAMAM-OH树枝状聚合物的一个分子。通过流式细胞术、共聚焦显微镜和紫外/可见光谱法，使用人肺上皮癌A549细胞体外评价氟异硫氰酸酯（FITC）标记的树枝状聚合物-药物缀合物的细胞进入。通过测量前列腺素E2的抑制，将树枝状聚合物布洛芬缀合物的药理活性与纯布洛芬在不同时间点进行比较。显着量的共轭物进入细胞迅速在15分钟内。前列腺素的抑制，注意到在30分钟内的树枝状大分子-药物共轭物与1小时的游离布洛芬。结果表明，具有高药物有效载荷的树枝状聚合物通过增强细胞递送来提高药物的功效，并且可能产生快速的药理学反应。这些树枝状聚合物-药物缀合物可以通过连接抗体和配体进行进一步修饰以用于靶向药物递送。(c)2005爱思唯尔有限公司保留所有权利。
Dendrimers are emerging as a relatively new class of polymeric biomaterials with applications in drug delivery, and imaging. Achieving a high drug payload in dendrimers, and understanding the therapeutic effect of the dendrimer-drug conjugates are receiving increasing attention. A high drug payload nanodevice was obtained by covalent conjugation of ibuprofen to a polyamidoamine (PAMAM-G4-OH) dendrimer. Using DCC as a coupling agent, 58 molecules of ibuprofen were covalently conjugated to one molecule of generation 4 PAMAM-OH dendrimer. Cellular entry of the fluoroisothiocynate (FITC)-labeled dendrimer-drug conjugate was evaluated in vitro by using human lung epithelial carcinoma A549 cells by flow cytometry, confocal microscopy and UV/Visible spectroscopy. The pharmacological activity of the dendrimer ibuprofen conjugate was compared to pure ibuprofen at various time points by measuring the suppression of prostaglandin E2. Significant amounts of the conjugate entered the cells rapidly within 15 min. Suppression of prostaglandin was noted within 30 min for the dendrimer-drug conjugates versus 1 h for the free ibuprofen. The results suggest that dendrimers with high drug payload improve the drug's efficacy by enhanced cellular delivery, and may produce a rapid pharmacological response. These dendrimer-drug conjugates can potentially be further modified by attaching antibodies and ligands for targeted drug delivery. (c) 2005 Elsevier Ltd. All rights reserved.