A PEGylated dendritic nanoparticulate carrier of fluorouracil
A PEGylated dendritic nanoparticulate carrier of fluorouracil
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DOI：
10.1016/s0378-5173(03)00132-7
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发表时间：
2003-05-12
影响因子：
5.8
通讯作者：
Jain, NK
中科院分区：
文献类型：
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作者：
Bhadra, D;Bhadra, S;Jain, NK
本研究旨在开发和探索未包覆和聚乙二醇化的新型PAMAM树枝状大分子在抗癌药物5-氟尿嘧啶输送中的应用。本研究以乙二胺为核，甲基丙烯酸甲酯为引发剂，通过连续的Michael加成和穷尽酰胺化反应合成了4.0gPAMAM树枝状大分子。树枝状大分子用N-羟基琥珀酰亚胺活化的羧甲基mpeg-5000进行聚乙二醇化。红外光谱和核磁共振数据证明了合成的正确性。测定并比较了聚乙二醇化和非聚乙二醇化体系的各项理化参数、扫描电子显微镜、透射电子显微镜、最大吸收波长、溶血毒性、药物包封率、药物释放和血药浓度研究。聚乙二醇化反应提高了载药量，降低了药物释放速率和溶血毒性。透射电子显微镜研究揭示了该体系的表面性质。稳定性研究表明，它在室温和黑暗中是稳定的。体外和白化大鼠的血液水平研究发现，该系统适合于抗癌药物的长期给药，而不会产生任何明显的血液学障碍。聚乙二醇化被发现适合于PAMAM树枝状大分子的修饰，以减少药物泄漏和溶血毒性。这反过来可以提高载药能力，并稳定体内的这种系统。这项研究建议使用这种聚乙二醇化的树状大分子系统作为纳米颗粒储存库类型的给药系统。(C)2003 Elsevier Science B.V.保留所有权利。
The present study was aimed at developing and exploring the use of uncoated and PEGylated newer PAMAM dendrimers for delivery of anti-cancer drug 5-fluorouracil. For this study, successive Michael addition and exhaustive amidation reactions were used to synthesize 4.0G PAMAM dendrimers, using ethylenediamine as core and methylmethacrylate as propagating agent. The dendrimer was PEGylated using N-hydroxysuccinimide-activated carboxymethyl MPEG-5000. IR and NMR data proved the synthesis. Various physicochemical parameters, SEM, TEM, lambda(max) values, hemolytic toxicity, drug entrapment, drug release and blood-level studies of both PEGylated and non-PEGylated systems were determined and compared. The PEGylation of the systems was found to have increased their drug-loading capacity, reduced their drug release rate and hemolytic toxicity. TEM study revealed surface properties of the systems. Stability studies had shown its stability at room temperature in dark. The systems were found suitable for prolonged delivery of an anti-cancer drug by in vitro and blood-level studies in albino rats, without producing any significant hematological disturbances. PEGylation has been found to be suitable for modification of PAMAM dendrimers for reduction of drug leakage and hemolytic toxicity. This, in turn, could improve drug-loading capacity and stabilize such systems in body. The study suggests use of such PEGylated dendrimeric systems as nanoparticulate depot type of system for drug administration. (C) 2003 Elsevier Science B.V. All rights reserved.