A Microfluidic Approach for Intracellular Delivery into Red Blood Cells: A Deeper Understanding of the Role of Chemical/Rheological Properties of the Cellular Suspension

IF 5.4 2区医学 Q3 ENGINEERING, BIOMEDICAL Annals of Biomedical Engineering Pub Date : 2025-02-19 DOI:10.1007/s10439-025-03678-2

Clara Bernardelli, Monica Piergiovanni, Elena Bianchi, Carmelo Carlo-Stella, Maria Laura Costantino, Giustina Casagrande

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Abstract

Red Blood Cells (RBCs) are a promising drug delivery system candidate for many drugs. Using autologous cells helps to overcome biocompatibility issues, while microfluidics allows accurate control of the intracellular delivery of molecules through fluidic shear stress. With the ultimate goal of exploiting this delivery technique for clinical applications, we investigate how the chemical/rheological characteristics of the suspension and the properties of the RBCs in different animals influence the delivery mechanism. As regard the suspension of RBC, we study the effects induced by the hematocrit and by the presence of proteins such as albumin (Bovine Serum Albumin—BSA). Regarding the cellular properties of RBCs, we aim to investigate the exportability of the technique to the RBC of the most used animal models and identify the most suitable one. The presence of BSA implies a more significant variability of the intracellular delivery. However, 70 ÷ 94% of the cells have successfully encapsulated the probe molecule. Regarding the effect of hematocrit, however, the implementation of the experiment is more challenging due to the increase in viscosity and the easier sedimentation at low flow rates. Evaluation of intracellular delivery in the RBCs of various animal samples has instead led to the proposal of the mouse as the most suitable model for preclinical studies on this particular delivery approach.

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细胞内递送至红细胞的微流体方法：对细胞悬浮液化学/流变特性作用的更深入理解。

红细胞是一种很有前途的药物传递系统。使用自体细胞有助于克服生物相容性问题，而微流体可以通过流体剪切应力精确控制细胞内分子的传递。为了将这种递送技术应用于临床，我们研究了悬浮液的化学/流变特性以及不同动物红细胞的特性如何影响递送机制。至于红细胞的悬浮，我们研究了红细胞压积和白蛋白（牛血清白蛋白- bsa）等蛋白质的存在所引起的影响。关于红细胞的细胞特性，我们的目的是研究该技术在最常用动物模型的红细胞中的可移植性，并确定最合适的方法。BSA的存在意味着细胞内递送的变异性更显著。然而，70% / 94%的细胞成功封装了探针分子。然而，关于红细胞压积的影响，由于粘度增加，在低流速下更容易沉淀，因此实验的实施更具挑战性。对各种动物样本红细胞细胞内递送的评估导致了小鼠作为这种特定递送方法的最合适的临床前研究模型的建议。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Biomedical Engineering 工程技术-工程：生物医学

CiteScore

7.50

自引率

15.80%

发文量

212

审稿时长

3 months

期刊介绍： Annals of Biomedical Engineering is an official journal of the Biomedical Engineering Society, publishing original articles in the major fields of bioengineering and biomedical engineering. The Annals is an interdisciplinary and international journal with the aim to highlight integrated approaches to the solutions of biological and biomedical problems.