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通过电喷雾制备的稳定干燥过氧化氢酶颗粒。

Stable Dried Catalase Particles Prepared by Electrospraying.

作者信息

Schlosser Corinna S, Brocchini Steve, Williams Gareth R

机构信息

UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.

出版信息

Nanomaterials (Basel). 2022 Jul 20;12(14):2484. doi: 10.3390/nano12142484.

Abstract

Therapeutic proteins and peptides are clinically important, offering potency while reducing the potential for off-target effects. Research interest in developing therapeutic polypeptides has grown significantly during the last four decades. However, despite the growing research effort, maintaining the stability of polypeptides throughout their life cycle remains a challenge. Electrohydrodynamic (EHD) techniques have been widely explored for encapsulation and delivery of many biopharmaceuticals. In this work, we explored monoaxial electrospraying for encapsulation of bovine liver catalase, investigating the effects of the different components of the electrospraying solution on the integrity and bioactivity of the enzyme. The catalase was successfully encapsulated within polymeric particles made of polyvinylpyrrolidone (PVP), dextran, and polysucrose. The polysorbate 20 content within the electrospraying solution (50 mM citrate buffer, pH 5.4) affected the catalase loading-increasing the polysorbate 20 concentration to 500 μg/mL resulted in full protein encapsulation but did not prevent loss in activity. The addition of ethanol (20% ) to a fully aqueous solution improves the electrospraying process by reducing surface tension, without loss of catalase activity. The polymer type was shown to have the greatest impact on preserving catalase activity within the electrosprayed particles. When PVP was the carrier there was no loss in activity compared with fresh aqueous solutions of catalase. The optimum particles were obtained from a 20% PVP or 30% PVP-trehalose (1:1 ) solution. The addition of trehalose confers stability advantages to the catalase particles. When trehalose-PVP particles were stored at 5 °C, enzymatic activity was maintained over 3 months, whereas for the PVP-only analogue a 50% reduction in activity was seen. This demonstrates that processing catalase by monoaxial electrospraying can, under optimised conditions, result in stable polymeric particles with no loss of activity.

摘要

治疗性蛋白质和肽在临床上具有重要意义,它们在发挥药效的同时降低了脱靶效应的可能性。在过去的四十年中,开发治疗性多肽的研究兴趣显著增长。然而,尽管研究力度不断加大,但在多肽的整个生命周期内维持其稳定性仍然是一项挑战。电液动力学(EHD)技术已被广泛用于多种生物药物的包封和递送。在这项工作中,我们探索了单轴电喷雾法用于牛肝过氧化氢酶的包封,研究了电喷雾溶液不同成分对酶的完整性和生物活性的影响。过氧化氢酶成功地包封在由聚乙烯吡咯烷酮(PVP)、葡聚糖和聚蔗糖制成的聚合物颗粒中。电喷雾溶液(50 mM柠檬酸盐缓冲液,pH 5.4)中的吐温20含量影响过氧化氢酶的负载量——将吐温20浓度提高到500 μg/mL可实现蛋白质的完全包封,但无法防止活性丧失。向完全水溶液中添加乙醇(20%)可通过降低表面张力改善电喷雾过程,而过氧化氢酶活性没有损失。结果表明,聚合物类型对保持电喷雾颗粒中的过氧化氢酶活性影响最大。当以PVP为载体时,与新鲜的过氧化氢酶水溶液相比,活性没有损失。最佳颗粒是从20% PVP或30% PVP -海藻糖(1:1)溶液中获得的。添加海藻糖赋予了过氧化氢酶颗粒稳定性优势。当海藻糖 - PVP颗粒在5°C下储存时,酶活性在3个月内保持稳定,而仅含PVP的类似物活性降低了50%。这表明在优化条件下,通过单轴电喷雾法处理过氧化氢酶可得到活性无损失的稳定聚合物颗粒。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f96/9322511/31a747b076e9/nanomaterials-12-02484-g001.jpg

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