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Evaluation of Hybrid Vesicles in an Intestinal Cell Model Based on Structured Paper Chips
Biomacromolecules ( IF 5.5 ) Pub Date : 2021-08-23 , DOI: 10.1021/acs.biomac.1c00686
Paula De Dios Andres 1 , Isabella N Westensee 1 , Edit Brodszkij 1 , Miguel A Ramos-Docampo 1 , Noga Gal 1 , Brigitte Städler 1
Affiliation  

Cell culture-based intestinal models are important to evaluate nanoformulations intended for oral drug delivery. We report the use of a floating structured paper chip as a scaffold for Caco-2 cells and HT29-MTX-E12 cells that are two established cell types used in intestinal cell models. The formation of cell monolayers for both mono- and cocultures in the paper chip are confirmed and the level of formed cell–cell junctions is evaluated. Further, cocultures show first mucus formation between 6–10 days with the mucus becoming more pronounced after 19 days. Hybrid vesicles (HVs) made from phospholipids and the amphiphilic block copolymer poly(cholesteryl methacrylate)-block-poly(2-carboxyethyl acrylate) in different ratios are used as a representative soft nanoparticle to assess their mucopenetration ability in paper chip-based cell cultures. The HV assembly is characterized, and it is illustrated that these HVs cross the mucus layer and are found intracellularly within 3 h when the cells are grown in the paper chips. Taken together, the moist three-dimensional cellulose environment of structured paper chips offers an interesting cell culture-based intestinal model that can be further integrated with fluidic systems or online read-out opportunities.

中文翻译:

基于结构化纸芯片的肠细胞模型中混合囊泡的评估

基于细胞培养的肠道模型对于评估用于口服给药的纳米制剂很重要。我们报告了使用浮动结构纸芯片作为 Caco-2 细胞和 HT29-MTX-E12 细胞的支架,它们是肠道细胞模型中使用的两种已建立的细胞类型。确认纸片中单培养和共培养的细胞单层的形成,并评估形成的细胞 - 细胞连接的水平。此外,共培养物在 6-10 天之间显示出第一次粘液形成,19 天后粘液变得更加明显。由磷脂和两亲性嵌段共聚物聚(甲基丙烯酸胆固醇酯)-嵌段制成的杂化囊泡 (HV)使用不同比例的聚(2-羧乙基丙烯酸酯)作为代表性的软纳米颗粒,以评估它们在基于纸片的细胞培养物中的粘液渗透能力。HV 组件的特征在于,当细胞在纸片中生长时,这些 HV 穿过粘液层并在 3 小时内在细胞内发现。总之,结构化纸芯片潮湿的三维纤维素环境提供了一个有趣的基于细胞培养的肠道模型,可以进一步与流体系统或在线读出机会相结合。
更新日期:2021-09-13
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