The Hepatosplenic Surgery Center, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150001, China.
AAPS PharmSciTech. 2012 Jun;13(2):441-7. doi: 10.1208/s12249-012-9756-9. Epub 2012 Feb 29.
Pluronic F127 (PF-127) shows thermoreversible property, which is of the utmost interest in optimizing drug formulation and delivery. However, its hitherto unresolved drawback of a low phase transition temperature (T (tr)) has limited its application in injectable drug delivery systems. We have recently synthesized a new type of PF-127 copolymers with higher T (tr) using a simple oxidative method. Here, we have investigated the drug-releasing feature of oxidized PF-127 and oxidized PF-127-containing silver nanoparticles (SNPs), carrying arsenic trioxide (ATO), in a subcutaneous model of rats. Injectable hydrogels prepared with oxidized PF-127s were less viscous and easier to inject, at the same concentration, than their precursor. Addition of SNPs further elevated T (tr), resulting in even lower viscosity of the injectable hydrogel prepared from SNP-containing oxidized PF-127. The oxidized PF-127 copolymers did not differ significantly in ATO-releasing ability, compared with parental PF-127, but the addition of SNPs altered the ATO-releasing feature of oxidized PF-127 to some extent. ATO-carrying oxidized PF-127s had similar toxicity, but the addition of SNPs enhanced the hepatotoxicity of ATO, as evidenced by elevated serum levels of alanine aminotransferase and aspartate aminotransferase and histological alterations, compared to parental PF-127. The results presented herein warrant further investigation of the modified PF-127 copolymers to deliver ATO or other drugs in the form of injectable hydrogels.
泊洛沙姆 F127（PF-127）具有热可逆性，这对于优化药物配方和递送至关重要。然而，其迄今为止尚未解决的低相变温度（T(tr)）的缺点限制了其在可注射药物递送系统中的应用。我们最近使用简单的氧化方法合成了一种新型具有更高 T(tr)的 PF-127 共聚物。在这里，我们研究了氧化 PF-127 和载有三氧化二砷（ATO）的氧化 PF-127 载银纳米粒子（SNPs）在大鼠皮下模型中的释药特征。与前体相比，相同浓度下，用氧化 PF-127 制备的可注射水凝胶的粘性更小，更容易注射。添加 SNPs 进一步提高了 T(tr)，导致载 SNP 的氧化 PF-127 制备的可注射水凝胶的粘性更低。与母体 PF-127 相比，氧化 PF-127 共聚物在 ATO 释放能力方面没有显著差异，但添加 SNPs 在某种程度上改变了氧化 PF-127 的 ATO 释放特征。载 ATO 的氧化 PF-127 具有相似的毒性，但添加 SNPs 增强了 ATO 的肝毒性，这表现在血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平升高和组织学改变方面，与母体 PF-127 相比。本文的结果证明，需要进一步研究修饰后的 PF-127 共聚物，以可注射水凝胶的形式递送 ATO 或其他药物。
