Scholarlink

<p> Our previous research identified that an oral mPEG-<i>b</i>-PCL polymeric micelle (PM) maintained satisfactory integrity but exhibited limited transcytosis efficiency. To enhance transcytosis and enable ROS-responsive release, we developed a series of hybrid PMs by blending a synthesized L-carnitine-grafted, thioketal-linked LC-PEG<sub>5k</sub>-TK-PCL<sub>7k</sub> polymer with mPEG<sub>5k</sub>-PCL<sub>7k</sub>. These hybrid PMs, similar in particle size (120&#xa0;nm) and drug loading (10%) to the PM composed of pure mPEG<sub>5k</sub>-PCL<sub>7k</sub> (5-7E), retained good stability in SGF and SIF. However, the hybrid PM with a 40% LC-PEG<sub>5k</sub>-TK-PCL<sub>7k</sub> proportion showed reduced integrity and penetration in mucus layer. In Caco-2/E12 (7:3) cells, the hybrid PM with a 20% LC-PEG<sub>5k</sub>-TK-PCL<sub>7k</sub> proportion (20%Hybrid 5-7E) demonstrated superior uptake, low cytotoxicity, and a 3.37-fold higher transcytosis than that of 5-7E. In 4T1 cells, prepared PMs exhibited similar uptake but hybrid PMs showed obvious ROS-responsive dissociation and cytotoxicity. The in vivo integrity and biocompatibility of 20%Hybrid 5-7E were confirmed by plasma concentration and hemolysis test, and the bio-distribution results demonstrated its tumor accumulation. Pharmacokinetics revealed a 10-fold increase in docetaxel (DTX) bioavailability due to the 20%Hybrid 5-7E encapsulation. Consequently, orally administered 20%Hybrid 5-7E (DTX 40&#xa0;mg/kg) achieved comparable antitumor activity but reduced systemic toxicity relative to intravenously injected DTX solution (10&#xa0;mg/kg) in 4T1 tumor-bearing BALB/c mice.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

OCTN2-targeted and ROS-responsive hybrid polymeric micelles for oral delivery of docetaxel

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月27日

查看全文
  • Haihan Sun,
  • Jingxin Gou,
  • Xiaoshuang Bi,
  • Jiayin Song,
  • Boyuan Liu,
  • Xiaoyu Jin,
  • Bowen Sui,
  • Xiangqun Jin

摘要

Our previous research identified that an oral mPEG-b-PCL polymeric micelle (PM) maintained satisfactory integrity but exhibited limited transcytosis efficiency. To enhance transcytosis and enable ROS-responsive release, we developed a series of hybrid PMs by blending a synthesized L-carnitine-grafted, thioketal-linked LC-PEG5k-TK-PCL7k polymer with mPEG5k-PCL7k. These hybrid PMs, similar in particle size (120 nm) and drug loading (10%) to the PM composed of pure mPEG5k-PCL7k (5-7E), retained good stability in SGF and SIF. However, the hybrid PM with a 40% LC-PEG5k-TK-PCL7k proportion showed reduced integrity and penetration in mucus layer. In Caco-2/E12 (7:3) cells, the hybrid PM with a 20% LC-PEG5k-TK-PCL7k proportion (20%Hybrid 5-7E) demonstrated superior uptake, low cytotoxicity, and a 3.37-fold higher transcytosis than that of 5-7E. In 4T1 cells, prepared PMs exhibited similar uptake but hybrid PMs showed obvious ROS-responsive dissociation and cytotoxicity. The in vivo integrity and biocompatibility of 20%Hybrid 5-7E were confirmed by plasma concentration and hemolysis test, and the bio-distribution results demonstrated its tumor accumulation. Pharmacokinetics revealed a 10-fold increase in docetaxel (DTX) bioavailability due to the 20%Hybrid 5-7E encapsulation. Consequently, orally administered 20%Hybrid 5-7E (DTX 40 mg/kg) achieved comparable antitumor activity but reduced systemic toxicity relative to intravenously injected DTX solution (10 mg/kg) in 4T1 tumor-bearing BALB/c mice.

Graphical Abstract