Scholarlink

<p>Effective siRNA therapy requires efficient delivery systems. However, sustained-release technologies remain poorly developed. A novel coacervate-based formulation that enables the controlled release of siRNA-loaded polyion complex micelles was developed in this study. An ABA-type triblock copolymer (catiomer–polyethylene glycol–catiomer) and an AB-type diblock copolymer were blended at defined ratios (<i>f</i><sub>Tri</sub>) and complexed with siRNA/aniomer mixtures (<i>f</i><sub>siRNA</sub>) to form polyion complex assemblies. Certain formulations generated micelles at ambient temperature, which thermally transitioned into coacervated microparticles (transition temperature: 45 °C at <i>f</i><sub>Tri</sub> = <i>f</i><sub>siRNA</sub> = 0.4) and reverted to micelles upon cooling. At 37 °C, the coacervates released siRNA and micelles at a constant rate. Cytotoxicity was negligible after 24 h but increased after 72 h. Early-stage uptake (≤3 d), assessed using flow cytometry and confocal microscopy, revealed superior internalization for coacervates versus micelles, primarily via small PIC species, considering the release behavior of the initial stage. Luciferase knockdown assays confirmed enhanced gene silencing for the coacervate-treatment groups, as compared to the micelle-treated groups, although the overall efficiency remained modest. These findings demonstrate that coacervate-based formulations enable sustained siRNA release and improved cellular uptake, as compared with micelles, highlighting their potential as next-generation delivery systems.</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

Block-copolymer-based coacervates enabling constant and sustained release of siRNA-containing polyion complex micelles

  • 期刊论文

  • 发表日期：

    2025年12月18日

查看全文
  • Ziwei Ma,
  • Hiroshi Kamizawa,
  • Rento Ota,
  • Bing Jhang Li,
  • Fadlina Aulia,
  • Teruki Nii,
  • Takeshi Mori,
  • Yoshiki Katayama,
  • Akihiro Kishimura

摘要

Effective siRNA therapy requires efficient delivery systems. However, sustained-release technologies remain poorly developed. A novel coacervate-based formulation that enables the controlled release of siRNA-loaded polyion complex micelles was developed in this study. An ABA-type triblock copolymer (catiomer–polyethylene glycol–catiomer) and an AB-type diblock copolymer were blended at defined ratios (fTri) and complexed with siRNA/aniomer mixtures (fsiRNA) to form polyion complex assemblies. Certain formulations generated micelles at ambient temperature, which thermally transitioned into coacervated microparticles (transition temperature: 45 °C at fTri = fsiRNA = 0.4) and reverted to micelles upon cooling. At 37 °C, the coacervates released siRNA and micelles at a constant rate. Cytotoxicity was negligible after 24 h but increased after 72 h. Early-stage uptake (≤3 d), assessed using flow cytometry and confocal microscopy, revealed superior internalization for coacervates versus micelles, primarily via small PIC species, considering the release behavior of the initial stage. Luciferase knockdown assays confirmed enhanced gene silencing for the coacervate-treatment groups, as compared to the micelle-treated groups, although the overall efficiency remained modest. These findings demonstrate that coacervate-based formulations enable sustained siRNA release and improved cellular uptake, as compared with micelles, highlighting their potential as next-generation delivery systems.