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冷冻干燥作为一种多功能工艺在改善医用凝胶性能方面的作用。

The Role of Freeze-Drying as a Multifunctional Process in Improving the Properties of Hydrogels for Medical Use.

作者信息

Odziomek Kacper, Drabczyk Anna K, Kościelniak Paulina, Konieczny Patryk, Barczewski Mateusz, Bialik-Wąs Katarzyna

机构信息

Cracow University of Technology, Faculty of Chemical Engineering and Technology, Department of Organic Chemistry and Technology, 24 Warszawska Street, 31155 Cracow, Poland.

Institute of Human Biology and Evolution, Faculty of Biology, Adam Mickiewicz University, 6 Uniwersytetu Poznanskiego Street, 61614 Poznan, Poland.

出版信息

Pharmaceuticals (Basel). 2024 Nov 10;17(11):1512. doi: 10.3390/ph17111512.

Abstract

Freeze-drying is a dehydration method that extends the shelf life and stability of drugs, vaccines, and biologics. Recently, its role has expanded beyond preservation to improve novel pharmaceuticals and their carriers, such as hydrogels, which are widely studied for both drug delivery and wound healing. The main aim of this study was to explore the multifunctional role of freeze-drying in improving the physicochemical properties of sodium alginate/poly(vinyl alcohol)-based hydrogels for medical applications. The base matrix and hydrogels containing a nanocarrier-drug system, were prepared by chemical cross-linking and then freeze-dried for 24 h at -53 °C under 0.2 mBa. Key analyses included determination of gel fraction, swelling ratio, FT-IR, SEM, TG/DTG, in vitro drug release and kinetics, and cytotoxicity assessment. Freeze-drying caused an increase in the gel fraction of the hydrogel with the dual drug delivery system from 55 ± 1.6% to 72 ± 0.5%. Swelling ability was pH-dependent and remained in the same range (175-282%). Thermogravimetric analysis showed that freeze-dried hydrogels exhibited higher thermal stability than their non-freeze-dried equivalents. The temperature at 10% weight loss increased from 194.0 °C to 198.9 °C for the freeze-dried drug-loaded matrix, and from 188.4 °C to 203.1 °C for the freeze-dried drug-free matrix. The average pore size of the freeze-dried hydrogels was in the range of 1.07 µm ± 0.54 to 1.74 µm ± 0.92. In vitro drug release revealed that active substances were released in a controlled and prolonged way, according to the Korsmeyer-Peppas model. The cumulative amount of salicylic acid released at pH = 9.0 after 96 h was 63%, while that of fluocinolone acetonide reached 73%. Both hydrogels were non-toxic to human fibroblast cells, maintaining over 90% cell viability after 48 h of incubation. The results show a high potential for commercialisation of the obtained hydrogels as medical dressings.

摘要

冷冻干燥是一种可延长药物、疫苗和生物制品保质期及稳定性的脱水方法。最近,其作用已从单纯的保存扩展到改善新型药物及其载体,如水凝胶,水凝胶在药物递送和伤口愈合方面都得到了广泛研究。本研究的主要目的是探索冷冻干燥在改善用于医学应用的海藻酸钠/聚乙烯醇基水凝胶的物理化学性质方面的多功能作用。通过化学交联制备含纳米载体 - 药物系统的基础基质和水凝胶,然后在 -53°C、0.2 mBa 条件下冷冻干燥 24 小时。关键分析包括凝胶分数、溶胀率、傅里叶变换红外光谱(FT - IR)、扫描电子显微镜(SEM)、热重/微商热重(TG/DTG)、体外药物释放及动力学以及细胞毒性评估。冷冻干燥使具有双药物递送系统的水凝胶的凝胶分数从 55±1.6%增加到 72±0.5%。溶胀能力依赖于 pH 值,且保持在相同范围(175 - 282%)。热重分析表明,冷冻干燥的水凝胶比未冷冻干燥的同类水凝胶表现出更高的热稳定性。对于负载药物的冷冻干燥基质,失重 10%时的温度从 194.0°C 升高到 198.9°C,对于无药物的冷冻干燥基质,该温度从 188.4°C 升高到 203.1°C。冷冻干燥水凝胶的平均孔径在 1.07 µm±0.54 至 1.74 µm±0.92 范围内。体外药物释放表明,根据 Korsmeyer - Peppas 模型,活性物质以可控且持久的方式释放。在 pH = 9.0 条件下 96 小时后,水杨酸的累积释放量为 63%,而醋酸氟轻松达到 73%。两种水凝胶对人成纤维细胞均无毒,孵育 48 小时后细胞活力保持在 90%以上。结果表明所获得的水凝胶作为医用敷料具有很高的商业化潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fca/11597604/0f8431243bd8/pharmaceuticals-17-01512-g001.jpg

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