在乙醇中合成无定形碳酸钙纳米颗粒及其在水介质中的稳定性的环保工艺,Green Chemistry

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在乙醇中合成无定形碳酸钙纳米颗粒及其在水介质中的稳定性的环保工艺
Green Chemistry ( IF 9.3 ) Pub Date : 2022-01-13 , DOI: 10.1039/d1gc03396d
Lauriane Chuzeville _{1,

2} , Frank Boury ₃ , David Duday ₁ , Resmi Anand ₁ , Enzo Moretto _{1,

2} , Jean-Sébastien Thomann ₁

Affiliation

无定形碳酸钙纳米粒子（ACC NPs）是用于医疗保健应用的有前途的多功能材料。由于它们在水介质中的不稳定性，用于生物医学领域的纯 ACC NPs 越来越多地使用氨扩散法 (ADM) 在无水乙醇中合成。尽管该方法具有无需添加剂即可提供稳定的 ACC NPs 的优势，但它需要使用纯乙醇作为溶剂。本文介绍了使用气体扩散在乙醇中形成 ACC NPs 的新见解。根据这些发现对工艺进行优化可以将 ACC NPs 的质量浓度提高 3.5 倍。结果，生产目标质量颗粒所需的乙醇量显着减少，从而减少了该过程的生态影响。所得 ACC NPs 在水性介质中的稳定性是通过使用基于乙醇注射法的磷脂的短时间过程来实现的。通过利用带负电荷的材料对乙醇中 ACC NPs 正表面的自然静电亲和力，与最接近的现有技术相比，我们将处理时间从 24 小时减少到 2 分钟，从而减少了操作时间和相应的能耗。该过程不需要使用合成的聚乙二醇化脂质进行空间稳定。此外，天然鸡蛋来源的磷脂首次被鉴定为有效的稳定剂。使用用于批量合成的 50 L 反应器以及用于工业连续流生产的连续流反应器成功地证明了我们工艺的升级。

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Eco-friendly processes for the synthesis of amorphous calcium carbonate nanoparticles in ethanol and their stabilisation in aqueous media

Amorphous calcium carbonate nanoparticles (ACC NPs) are promising multifunctional materials for healthcare applications. Due to their instability in aqueous media, pure ACC NPs for the biomedical field are increasingly synthesised in absolute ethanol, using the ammonia diffusion method (ADM). Although this method presents the advantage of providing stable ACC NPs without additives, it requires the use of pure ethanol as solvent. New insights into the formation mechanisms of ACC NPs in ethanol using gas diffusion are presented in this article. The optimisation of the process according to these findings can increase the mass concentration of ACC NPs by a factor of 3.5. As a result, the amount of ethanol required to produce a target mass of particles is significantly decreased, reducing the ecological impact of the process. The stabilisation of the resulting ACC NPs in aqueous media is achieved by a short-time process using phospholipids based on the ethanol injection method. By using the natural electrostatic affinity of negatively charged materials for the positive surface of ACC NPs in ethanol, we reduced the process time from 24 h to 2 minutes, compared with the closest state of the art, decreasing the operating time and corresponding energy consumption. The process does not require the use of synthetic PEGylated lipids for steric stabilisation. In addition, a natural egg-sourced phospholipid was identified as an efficient stabiliser for the first time. The upscaling of our process was successfully demonstrated using a 50 L reactor for bulk synthesis, as well as a continuous flow reactor for industrial continuous flow production.

更新日期：2022-01-13

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