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作为载体系统的水凝胶微胶囊的制备。

Fabrication of hydrogel mini-capsules as carrier systems.

作者信息

Roberti Elisa, Petrucci Gaia, Bianciardi Francesco, Palagi Stefano

机构信息

The BioRobotics Institute, Sant'Anna School of Advanced Studies, Pisa, Tuscany, 56025, Italy.

Department of Excellence in Robotics & AI, Sant'Anna School of Advanced Studies, Pisa, Tuscany, 56127, Italy.

出版信息

Open Res Eur. 2024 Oct 25;3:191. doi: 10.12688/openreseurope.16723.2. eCollection 2023.

Abstract

Conventional drug administration often results in systemic action, thus needing high dosages and leading to potentially pronounced side effects. Targeted delivery, employing carriers like nanoparticles, aims to release drugs at a target site, but only a small fraction of nanoparticles actually reaches it. Microrobots have been proposed to overcome this issue since they can be guided to hard-to-reach sites and locally deliver payloads. To enhance their functionality, we propose microrobots made as deformable capsules with hydrogel shells and aqueous cores, having the potential added advantages of biocompatibility, permeability, and stimulus-responsiveness. Endowing microrobots with deformability could allow them to navigate inside capillaries and cross barriers to finally reach the target site. In this study, we present a cost-effective method for fabricating core-shell structures without the use of organic solvents, surfactants, or extreme pH conditions unlike other techniques (e.g. Layer by Layer). The process begins with the dripping of a mixture of hydrogels, agarose and alginate, into a solution to gelate the drops into beads. After they are loaded with calcium ions at different concentrations, they are immersed in an alginate solution to form the shell. Finally, the beads are heated to let the agarose melt and diffuse out, leaving a liquid core. By varying the concentration of calcium ions, we obtain shells of different thicknesses. To estimate it, we have developed a method using the colour intensity from microscope images. This allowed us to observe that lowering the calcium ions concentration below a threshold does not lead to the formation of continuous shells. For higher concentrations, although the core may remain partially gelled, continuous shells successfully form. Therefore, our fabrication process could find applications in drug delivery, encapsulation systems, and microrobotics.

摘要

传统的药物给药方式往往会产生全身作用,因此需要高剂量用药,并可能导致明显的副作用。靶向给药利用纳米颗粒等载体,旨在将药物释放到靶位点,但实际上只有一小部分纳米颗粒能到达该位点。由于微型机器人可以被引导至难以到达的部位并在局部递送药物,因此有人提出用其来解决这一问题。为了增强其功能,我们提出制作一种具有水凝胶外壳和水性内核的可变形胶囊形式的微型机器人,其具有生物相容性、渗透性和刺激响应性等潜在的附加优势。赋予微型机器人可变形性可以使其在毛细血管内导航并穿越屏障,最终到达靶位点。在本研究中,我们提出了一种经济高效的方法来制造核壳结构,与其他技术(如层层组装法)不同,该方法无需使用有机溶剂、表面活性剂或极端的pH条件。该过程始于将水凝胶、琼脂糖和藻酸盐的混合物滴入一种溶液中,使液滴凝胶化形成珠子。在它们加载不同浓度的钙离子后,将其浸入藻酸盐溶液中以形成外壳。最后,将珠子加热以使琼脂糖熔化并扩散出来,留下液体内核。通过改变钙离子的浓度,我们获得了不同厚度的外壳。为了估计外壳厚度,我们开发了一种利用显微镜图像颜色强度的方法。这使我们观察到,将钙离子浓度降低到阈值以下不会导致连续外壳的形成。对于较高浓度,尽管内核可能仍会部分凝胶化,但连续外壳仍能成功形成。因此,我们的制造工艺可应用于药物递送、封装系统和微型机器人技术。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69e5/11605177/e2b34f3c8cf4/openreseurope-3-20144-g0000.jpg

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