Poly(ethylene oxide)-modified poly(β-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs:: Part 2.: In vivo distribution and tumor localization studies
Poly(ethylene oxide)-modified poly(β-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs:: Part 2.: In vivo distribution and tumor localization studies
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DOI：
10.1007/s11095-005-8343-0
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发表时间：
2005-12-01
影响因子：
3.7
通讯作者：
Amiji, M
中科院分区：
文献类型：
--
作者：
Shenoy, D;Little, S;Amiji, M
目的。本研究的目的是确定聚环氧乙烷 (PEO) 修饰的聚 (β-氨基酯) (PbAE) 的生物分布特征和肿瘤定位潜力，作为一种新型、pH 敏感的可生物降解聚合物纳米颗粒系统，用于肿瘤靶向药物输送。方法。 PEO 修饰的 PbAE 和 PEO 修饰的聚（ε-己内酯）（PCL）（一种非 pH 敏感聚合物）纳米颗粒系统的生物分布研究是在正常小鼠中进行的，使用（111）铟-氧杂环己烷 [In-111] 作为封装在聚合物基质内的亲脂性放射性标记，并研究了静脉注射后纳米颗粒在血浆和所有重要器官中的分布。使用人卵巢癌异种移植物（SKOV-3）在裸鼠上形成实体瘤，并检查血液、肿瘤块和肝脏中封装在聚合物纳米颗粒中的氚[H-3]标记的紫杉醇的浓度变化。结果。对正常小鼠的伽马发射同位素 [In-111] 进行的研究对 PEO 修饰的纳米颗粒载体系统进行了彻底的生物分布分析，而 H-3-紫杉醇可用于直接了解抗癌化合物在主要分布部位的浓度变化和肿瘤定位。 PEO-PbAE 和 PEO-PCL 纳米颗粒均通过含 PEO 的三嵌段嵌段共聚物 (Pluronic (R)) 稳定剂进行表面改性，显示出长的系统循环特性。尽管 PCL 纳米颗粒显示出网状内皮系统更高的吸收，但 PbAE 纳米颗粒有效地将封装的有效负载递送到肿瘤块中。结论。 PEO 修饰的 PbAE 纳米粒子通过增强渗透和保留 (EPR) 机制在生物分布的早期阶段显示出相当大的被动肿瘤靶向潜力。这促使对纳米载体进行长时间的详细生物分布分析，为递送系统的优越性提供确凿的证据。
Purpose. This study was carried out to determine the biodistribution profiles and tumor localization potential of poly(ethylene oxide) (PEO)-modified poly(beta-amino ester) (PbAE) as a novel, pH-sensitive biodegradable polymeric nanoparticulate system for tumor-targeted drug delivery.Methods. The biodistribution studies of PEO-modified PbAE and PEO-modified poly(epsilon-caprolactone) (PCL), a non-pH-sensitive polymer, nanoparticle systems were carried out in normal mice using (111)indium-oxine [In-111] as a lipophilic radiolabel encapsulated within the polymeric matrix, and the distribution of the nanoparticles was studied in plasma and all the vital organs following intravenous administration. Solid tumors were developed on nude mice using human ovarian carcinoma xenograft (SKOV-3) and the change in concentrations of tritium [H-3]-labeled paclitaxel encapsulated in polymeric nanoparticles was examined in blood, tumor mass, and liver.Results. Study in normal mice with a gamma-emitting isotope [In-111] provided a thorough biodistribution analysis of the PEO-modified nanoparticulate carrier systems, whereas H-3-paclitaxel was useful to understand the change in concentration and tumor localization of anticancer compound directly in major sites of distribution. Both PEO-PbAE and PEO-PCL nanoparticles showed long systemic circulating properties by virtue of surface modification with PEO-containing triblock block copolymer (Pluronic (R)) stabilizer. Although the PCL nanoparticles showed higher uptake by the reticuloendothelial system, the PbAE nanoparticles effectively delivered the encapsulated payload into the tumor mass.Conclusions. PEO-modified PbAE nanoparticles showed considerable passive tumor targeting potential in early stages of biodistribution via the enhanced permeation and retention (EPR) mechanism. This prompts a detailed biodistribution profiling of the nanocarrier for prolonged periods to provide conclusive evidence for superiority of the delivery system.