Cisplatin delivery from poly(acrylic acid-co-methyl methacrylate) microparticles
Cisplatin delivery from poly(acrylic acid-co-methyl methacrylate) microparticles
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DOI：
10.1016/j.jconrel.2005.05.005
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发表时间：
2005-08-18
影响因子：
10.8
通讯作者：
Gemeinhart, RA
中科院分区：
文献类型：
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作者：
Yan, XL;Gemeinhart, RA
为了开发肿瘤化疗的平台，合成了聚(丙烯酸-甲基丙烯酸甲酯)微粒。含有羧酸盐的单体被包括在复杂的治疗药物中，特别是顺铂。在水介质中，采用自由基乳液聚合法制备了微米级粒子。考察了顺铂微球和未载药微球的粒径、Zeta电位、体外细胞毒性和体内急性毒性。用体外细胞毒性和FT-IR对顺铂微球的释药进行表征。丙烯酸进料摩尔分数决定了几个关键的微粒特性，包括颗粒大小、Zeta-电位和产率。顺铂在第一天突然释放(40%)，随后是零级释放阶段。顺铂和微粒之间的相互作用使顺铂在接下来的五天里增加了大约20%的释放。顺铂负载和卸载的微粒对体外试验中使用的细胞系是无毒的(LC50；>15 mm)。从载顺铂微粒中释放的顺铂仍具有活性，但活性略低于新制备的顺铂。除了顺铂活性略有降低外，微球在体内的急性毒性较低(LD50和GT；170 mg/kg)，这表明该水凝胶微粒系统及其水凝胶包合机理值得进一步研究以用于药物输送。(C)2005爱思唯尔B.V.保留所有权利。
To develop a platform for tumor chemotherapy, poly(acrylic acid-co-methyl methacrylate) microparticles have been synthesized. Carboxylate containing monomers were included to complex therapeutic agents, specifically cisplatin. Microparticles were prepared by free radical emulsion polymerization in aqueous media. Particle diameter, zeta-potential, in vitro cytotoxicity, and in vivo acute toxicity were characterized for both cisplatin-loaded microparticles and unloaded microparticles. In vitro cytotoxicity and FT-IR were used to characterize cisplatin released from cisplatin-loaded microparticles. Acrylic acid feed mole fraction determined several key microparticle properties, including particle size, zeta-potential, and yield. A burst release of cisplatin (40%) in the first day was followed by a zero-order release phase. The interaction between cisplatin and microparticles allowed approximately 20% additional cisplatin release in the next five days. Cisplatin-loaded and unloaded microparticles are non-toxic (LC50 > 15 mM) to the cell line used in in vitro tests. Cisplatin released from cisplatin-loaded microparticles retained activity, but that activity was slightly lower than freshly prepared cisplatin. Other than a slight reduction in cisplatin activity, microparticles exhibited low in vivo acute toxicity (LD50 > 170 mg/kg), which suggests that this hydrogel particulate system and the hydrogel complexation mechanism should further be studied for drug delivery. (c) 2005 Elsevier B.V All rights reserved.