微流体技术可控制备可缓释纳米颗粒的微米组装体

张厚兵; 田泰宇; 冯琦; 何欣榆; 都小姣; 董华; 熊梦华; 闫立峰; 王均

doi:10.11777/j.issn1000-3304.2020.20090

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微流体技术可控制备可缓释纳米颗粒的微米组装体

论文 | 更新时间：2021-01-26

- 微流体技术可控制备可缓释纳米颗粒的微米组装体
- Microfluidic Preparation of Microparticles Capable of Sustained Release of Nanoparticles
- 高分子学报 2020年51卷第11期页码：1240-1247
- 作者机构：
  
  1.中国科学技术大学合肥微尺度物质科学国家研究中心　合肥 230027
  2.School of Biomedical Sciences and Engineering, Guangzhou International Campus,
  3. 广州市第一人民医院
  4. 医学院　广州 510006)
- 作者简介：
  
  E-mail: lfyan@ustc.edu.cn Li-feng Yan, E-mail: lfyan@ustc.edu.cn
  E-mail: mcjwang@scut.edu.cn Jun Wang, E-mail: mcjwang@scut.edu.cn
- 基金信息：
  
  国家自然科学基金(基金号 31900989)，广东省自然科学基金(基金号 2018A030310369)，广东省基础与应用基础研究基金(基金号 2020A1515011297)和中央高校基本科研业务费专项资金(基金号 2019JQ02)资助项目
- DOI：10.11777/j.issn1000-3304.2020.20090
  中图分类号：
- 纸质出版日期：2020-9-30，
  
  网络出版日期：2020-7-3，
  
  收稿日期：2020-4-1，
  
  修回日期：2020-4-30，
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张厚兵, 田泰宇, 冯琦, 何欣榆, 都小姣, 董华, 熊梦华, 闫立峰, 王均. 微流体技术可控制备可缓释纳米颗粒的微米组装体[J]. 高分子学报, 2020,51(11):1240-1247.

Hou-bing Zhang, Tai-yu Tian, Qi Feng, Xin-yu He, Xiao-jiao Du, Hua Dong, Meng-hua Xiong, Li-feng Yan, Jun Wang. Microfluidic Preparation of Microparticles Capable of Sustained Release of Nanoparticles[J]. Acta Polymerica Sinica, 2020,51(11):1240-1247.
张厚兵, 田泰宇, 冯琦, 何欣榆, 都小姣, 董华, 熊梦华, 闫立峰, 王均. 微流体技术可控制备可缓释纳米颗粒的微米组装体[J]. 高分子学报, 2020,51(11):1240-1247. DOI： 10.11777/j.issn1000-3304.2020.20090.

Hou-bing Zhang, Tai-yu Tian, Qi Feng, Xin-yu He, Xiao-jiao Du, Hua Dong, Meng-hua Xiong, Li-feng Yan, Jun Wang. Microfluidic Preparation of Microparticles Capable of Sustained Release of Nanoparticles[J]. Acta Polymerica Sinica, 2020,51(11):1240-1247. DOI： 10.11777/j.issn1000-3304.2020.20090.

摘要

作为药物递送载体，可缓释纳米颗粒的微米组装体具有可在局部滞留、缓释纳米颗粒从而促进药物组织渗透和细胞摄取等优点. 本研究利用微流体技术，发展了一类尺寸可控、可缓释纳米颗粒的微米组装体. 通过3-甲基马来酸酐-2-丙酸酯-聚己内酯(PCL-CDM)与聚酰胺-胺树枝状高分子(PAMAM)反应，获得可降解酰胺键桥连的两亲性高分子PCL-Dlinkm-PAMAM，通过控制二者投料比制备得到了接枝不同数量PCL的两亲性高分子(PCL-Dlinkm)

-PAMAM (

= 1 ~ 5). 利用微流体技术将(PCL-Dlinkm)

-PAMAM制备成微米组装体imCluster. imCluster主要通过PCL疏水相互作用组装形成，通过调控微流体水相和油相的流速，可实现尺寸从14 ~ 400 μm的精确控制. 使用接枝不同数量PCL的高分子(PCL-Dlinkm)

-PAMAM (

= 1 ~ 5)制备imCluster，当

= 1或2时，高分子组装形成形状不规则的微米级碎片；当

≥ 3时，高分子可组装形成稳定的球形imCluster. 当可降解酰胺键Dlinkm断裂后，PAMAM纳米颗粒可逐渐从imCluster释放.

Abstract

Microparticles that are capable of sustained release of nanoparticles have been widely used as drug delivery carriers for pulmonary delivery

oral delivery and intratumoral delivery

with the advantages of local retention and sustained release of nanoparticles to promote tissue penetration and cellular uptake of drugs. Herein

a strategy to prepare microparticles capable of sustainably releasing nanoparticles by droplet-based microfluidic approach was reported. Biodegradable amphiphilic polymers PCL-Dlinkm-PAMAMs were first synthesized through the reaction of 2-propionic-3-methylmaleic anhydride (CDM) modified poly(

-caprolactone) (PCL) and poly(amidoamine) dendrimer (PAMAM)

generating labile amide bonds. By tuning the feed ratio

a series of amphiphilic polymers with different PCL conjugates (PCL-Dlinkm)

-PAMAM (

= 1 − 5) were synthesized. With droplet-based microfluidic approach

these polymers were assembled into microparticles by the hydrophobic interaction of PCL segments. The size of microparticles was well-controlled by adjusting the ratio of flow rates of continuous phase and dispersed phase. It was found that regularly spherical microparticles (imCluster) were formed only when more than two PCL segments were conjugated on the amphiphilic polymer. These imCluster could sustainably release PAMAM nanoparticles after the cleavage of amide bonds in the aqueous solution. This study developed a class of microparticles with controlled size and capability of sustained release of nanoparticles.

关键词

纳米颗粒缓释微米组装体微流体技术可控制备可降解高分子

Keywords

Nanoparticle releaseMicroparticlesMicrofluidicsControlled preparationBiodegradable polymer

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