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可注射载脂双层囊泡的点击水凝胶微球用于释放大分子载药

Injectable liposome-containing click hydrogel microparticles for release of macromolecular cargos.

机构信息

Materials Science and Engineering, University of Delaware, Newark, DE, USA.

Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA.

出版信息

Soft Matter. 2024 Feb 21;20(8):1736-1745. doi: 10.1039/d3sm01009k.

Abstract

Hydrogel microparticles ranging from 0.1-100 μm, referred to as microgels, are attractive for biological applications afforded by their injectability and modularity, which allows facile delivery of mixed populations for tailored combinations of therapeutics. Significant efforts have been made to broaden methods for microgel production including the materials and chemistries by which they are made. droplet-based-microfluidics we have established a method for producing click poly-(ethylene)-glycol (PEG)-based microgels with or without chemically crosslinked liposomes (lipo-microgels) through the Michael-type addition reaction between thiol and either vinyl-sulfone or maleimide groups. Unifom spherical microgels and lipo-microgels were generated with sizes of 74 ± 16 μm and 82 ± 25 μm, respectively, suggesting injectability that was further supported by rheological analyses. Super-resolution confocal microscopy was used to further verify the presence of liposomes within the lipo-microgels and determine their distribution. Atomic force microscopy (AFM) was conducted to compare the mechanical properties and network architecture of bulk hydrogels, microgels, and lipo-microgels. Further, encapsulation and release of model cargo (FITC-Dextran 5 kDa) and protein (equine myoglobin) showed sustained release for up to 3 weeks and retention of protein composition and secondary structure, indicating their ability to both protect and release cargos of interest.

摘要

水凝胶微球的粒径范围为 0.1-100μm,被称为微凝胶,由于其可注射性和可模块化,在生物应用方面具有吸引力,这使得混合群体的输送变得容易,从而可以针对治疗方法进行定制组合。人们已经做出了巨大的努力来拓宽微凝胶生产的方法,包括它们的材料和化学性质。 在基于液滴的微流控技术中,我们通过巯基与乙烯基砜或马来酰亚胺基团之间的迈克尔加成反应,建立了一种生产点击聚(乙二醇)(PEG)基微凝胶的方法,其中可以包含或不包含化学交联的脂质体(脂质体微凝胶)。分别生成了尺寸为 74±16μm 和 82±25μm 的均匀球形微凝胶和脂质体微凝胶,表明具有可注射性,流变学分析进一步支持了这一点。超分辨率共聚焦显微镜被用于进一步验证脂质体在脂质体微凝胶中的存在,并确定其分布。原子力显微镜(AFM)用于比较体相水凝胶、微凝胶和脂质体微凝胶的机械性能和网络结构。此外,模型货物(FITC-葡聚糖 5kDa)和蛋白质(马肌红蛋白)的包封和释放表明,货物的释放可持续长达 3 周,并且保持蛋白质组成和二级结构,表明它们能够保护和释放感兴趣的货物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f9b/10880143/9e9a687bddec/d3sm01009k-f1.jpg

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