文献：Systemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles

文献链接：https://xueshu.baidu.com/usercenter/paper/show?paperid=fbb5ee6c22e98939bf638fa199c971a7

作者：Xue Yuan ,Qian Xie ,Keyu Su,Zhijie Li ,Dong Dong,Baojian Wu

相关产品：mPEG -block-PLGA 甲氧基聚乙二醇-聚乳酸羟基乙酸共聚物

原文摘要：Arenobufagin (ABG) is a major active component of toad venom, a traditional

Chinese medicine used for cancer therapy. However, poor aqueous solubility limits its

pharmacological studies in vivo due to administration difficulties. In this study, we aimed to

develop a polymeric nanomicelle (PN) system to enhance the solubility of ABG for effective

intravenous delivery. ABG-loaded PNs (ABG-PNs) were prepared with methoxy poly (ethylene

glycol)-block-poly (d,l-lactic-co-glycolic acid) (mPEG-PLGA) using the solvent-diffusion

technique. The obtained ABG-PNs were 105 nm in size with a small polydispersity index of

0.08. The entrapment efficiency and drug loading were 71.9% and 4.58%, respectively. Cellular

uptake of ABG-PNs was controlled by specific clathrin-mediated endocytosis. In addition,

ABG-PNs showed improved drug pharmacokinetics with an increased area under the curve

value (a 1.73-fold increase) and a decreased elimination clearance (37.8% decrease). The

nanomicelles showed increased drug concentrations in the liver and lung. In contrast, drug

concentrations in both heart and brain were decreased. Moreover, the nanomicelles enhanced

the anticancer effect of the pure drug probably via increased cellular uptake of drug molecules.

In conclusion, the mPEG-PLGA-based nanomicelle system is a satisfactory carrier for the

systemic delivery of ABG.

mpeg-PLGA是一种高分子材料。它由mpeg（甲氧基聚乙二醇）和PLGA（聚乳酸-羟基乙酸共聚物）组成。mpeg的引入赋予了材料良好的亲水性和生物相容性，使其在生物医学领域具有优势。PLGA则为材料提供了一定的机械强度和可降解性。这种材料可被制成纳米颗粒等多种形式，能够有效地负载ABG。聚合纳米胶（PN）系统，以提高ABG的溶解度。用甲氧基聚（乙二醇）块聚（d、l-乳酸共乙醇酸）（mPEG-PLGA）采用溶剂扩散技术制备ABG负载PNs（ABG-PNs）。过程如下：

图：ABG的化学结构

ABG-PNs的制备

采用溶剂扩散技术制备了ABG-PNs和ABG-PNs。简而言之，将固定数量的mPEG-PLGA和ABG溶解在乙醇溶液中。在磁性搅拌下，用注射器将得到的混合物快速注射到油酸钠中，生成胶束。残留的乙醇通过旋转蒸发器（在30°C的低压下）去除。

图：mpeg-PLGA

结论 ：mpeg-PLGA参与制备的ABG（ABG-PNs）的聚合胶束体通过增加水溶性促进了ABG的系统传递。此外，ABG-PNs显示化合物的药代动力学有所改善，AUC值有所提高。此外，纳米胶束可能通过增加细胞对化合物分子的摄取来增强作用。PNs是一种全身传递ABG的载体。