研究动态
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设计壳聚糖结肠递送微/纳米颗粒,用于具有抗结直肠癌细胞增殖活性的蓍草提取物。

Design of chitosan colon delivery micro/nano particles for an Achillea millefolium extract with antiproliferative activity against colorectal cancer cells.

发表日期:2024 Dec
作者: María de Las Nieves Siles-Sánchez, Irene Fernández-Jalao, Laura Jaime De Pablo, Susana Santoyo
来源: DRUG DELIVERY

摘要:

在这项研究中,采用低分子量壳聚糖(LCH)和中分子量壳聚糖(MCH)封装富含绿原酸和二咖啡酰奎尼酸(DCQA)的西洋蓍草提取物,该提取物对结肠腺癌细胞表现出抗增殖活性。通过使用两种不同的技术来设计 CH 微米/纳米颗粒以增加提取物结肠递送:离子凝胶化和喷雾干燥。获得的离子凝胶纳米颗粒比喷雾干燥微粒更小,产率更高,但喷雾干燥微粒在包封率 (EE) (> 94%) 方面表现出最佳性能,也允许包含更多量的提取物。对于所研究的所有酚类化合物,使用 LCH 设计的喷雾干燥微粒(LCH:提取物比率为 6:1 (1.25mg/mL))显示平均直径为 1.31±0.21μm,EE 值 > 93%。在胃肠道 pH 值(2 和 7.4)下,该制剂中包含的酚类化合物的释放曲线显示,大多数酚类化合物在初始释放量较小,随后在 1 小时内增加,并在长达 3 小时内保持恒定释放。绿原酸在 3 小时时表现出较高的释放值(pH 2 时为 56.91%;pH 7.4 时为 44.45%)。 3 小时时 DCQA 的释放范围为 9.01-40.73%,1,5-和 3,4-DCQA 的释放率更高。经过胃肠道消化后,67.65% 的绿原和大多数 DCQA 仍被包裹。因此,喷雾干燥微粒可以作为一种有前景的载体来增加西洋蓍草酚类化合物(主要是绿原酸和 DCQA)的结肠输送,这些化合物先前被描述为抗结直肠癌的潜在药物。
In this study, chitosan low molecular weight (LCH) and chitosan medium molecular weight (MCH) were employed to encapsulate a yarrow extract rich in chlorogenic acid and dicaffeoylquinic acids (DCQAs) that showed antiproliferative activity against colon adenocarcinoma cells. The design of CH micro/nanoparticles to increase the extract colon delivery was carried out by using two different techniques: ionic gelation and spray drying. Ionic gelation nanoparticles obtained were smaller and presented higher yields values than spray-drying microparticles, but spray-drying microparticles showed the best performance in terms of encapsulation efficiency (EE) (> 94%), also allowing the inclusion of a higher quantity of extract. Spray-drying microparticles designed using LCH with an LCH:extract ratio of 6:1 (1.25 mg/mL) showed a mean diameter of 1.31 ± 0.21 µm and EE values > 93%, for all phenolic compounds studied. The release profile of phenolic compounds included in this formulation, at gastrointestinal pHs (2 and 7.4), showed for most of them a small initial release, followed by an increase at 1 h, with a constant release up to 3 h. Chlorogenic acid presented the higher release values at 3 h (56.91% at pH 2; 44.45% at pH 7.4). DCQAs release at 3 h ranged between 9.01- 40.73%, being higher for 1,5- and 3,4-DCQAs. After gastrointestinal digestion, 67.65% of chlorogenic and most DCQAs remained encapsulated. Therefore, spray-drying microparticles can be proposed as a promising vehicle to increase the colon delivery of yarrow phenolics compounds (mainly chlorogenic acid and DCQAs) previously described as potential agents against colorectal cancer.