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微流控法将纳米颗粒包埋在通过竞争配体交换交联形成的海藻酸微凝胶中。

Microfluidic encapsulation of nanoparticles in alginate microgels gelled via competitive ligand exchange crosslinking.

机构信息

Department of Biophysics, Federal University of São Paulo, São Paulo, Brazil.

Department of Bioprocess and Materials Engineering, University of Campinas, Campinas, Brazil.

出版信息

Biopolymers. 2021 Jul;112(7):e23432. doi: 10.1002/bip.23432. Epub 2021 May 13.

DOI:10.1002/bip.23432
PMID:33982812
Abstract

Efficient delivery of nanometric vectors complexed with nanoparticles at a target tissue without spreading to other tissues is one of the main challenges in gene therapy. One means to overcome this problem is to confine such vectors within microgels that can be placed in a target tissue to be released slowly and locally. Herein, a conventional optical microscope coupled to a common smartphone was employed to monitor the microfluidic production of monodisperse alginate microgels containing nanoparticles as a model for the encapsulation of vectors. Alginate microgels (1.2%) exhibited an average diameter of 125 ± 3 μm, which decreased to 106 ± 5 μm after encapsulating 30 nm fluorescent nanoparticles. The encapsulation efficiency was 70.9 ± 18.9%. In a 0.1 M NaCl solution, 55 ± 5% and 92 ± 4.7% of nanoparticles were released in 30 minutes and 48 hours, respectively. Microgel topography assessment by atomic force microscopy revealed that incorporation of nanoparticles into the alginate matrix changes the scaffold's interfacial morphology and induces crystallization with the appearance of oriented domains. The high encapsulation rate of nanoparticles, alongside their continuous release of nanoparticles over time, makes these microgels and the production unit a valuable system for vector encapsulation for gene therapy research.

摘要

将与纳米颗粒复合的纳米载体递送到靶组织而不扩散到其他组织是基因治疗中的主要挑战之一。克服这个问题的一种方法是将这些载体限制在微凝胶内,将微凝胶放置在靶组织中可以缓慢且局部地释放。本文采用传统光学显微镜与普通智能手机相结合的方法,监测载有纳米颗粒的海藻酸钠微凝胶的微流体制备,以此作为载体包封的模型。海藻酸钠微凝胶(1.2%)的平均直径为 125 ± 3μm,封装 30nm 荧光纳米颗粒后直径减小至 106 ± 5μm。包封效率为 70.9 ± 18.9%。在 0.1 M NaCl 溶液中,纳米颗粒在 30 分钟和 48 小时内分别释放了 55 ± 5%和 92 ± 4.7%。原子力显微镜对微凝胶形貌的评估表明,纳米颗粒掺入海藻酸钠基质会改变支架的界面形态,并诱导结晶,出现取向畴。纳米颗粒的高包封率以及随着时间的推移持续释放纳米颗粒,使得这些微凝胶和生产单元成为基因治疗研究中载体包封的有价值系统。

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