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通过无定形的纳米受限 1-十四醇层控制介孔硅的药物释放。

Controlling drug release from mesoporous silica through an amorphous, nanoconfined 1-tetradecanol layer.

机构信息

"Ilie Murgulescu" Institute of Physical Chemistry, Romanian Academy of Sciences, 202 Splaiul Indepedentei, Bucharest 060021, Romania; University "Politehnica" of Bucharest, Faculty of Applied Chemistry and Material Science, 1-7 Polizu street, Bucharest 011061, Romania.

University "Politehnica" of Bucharest, Faculty of Applied Chemistry and Material Science, 1-7 Polizu street, Bucharest 011061, Romania.

出版信息

Eur J Pharm Biopharm. 2018 Jun;127:318-325. doi: 10.1016/j.ejpb.2018.02.020. Epub 2018 Mar 7.

Abstract

Mesoporous silica materials are promising nano-carriers for drug delivery systems. Even though there are many strategies for controlling the drug release kinetics, these must be adapted through trial and error on a case-by-case basis. Here we explore the possibility of tailoring the release kinetics of hydrophilic, water soluble therapeutic agents from mesoporous silica through addition of a hydrophobic excipient, 1-tetradecanol. In vitro drug release experiments performed at 37 °C, in phosphate buffer solution (pH 7.4) show that the addition of tetradecanol yields slower drug release kinetics, which was correlated with the presence of a liquid fatty alcohol interfacial layer. The layer mass is 11-23 wt.% of the metoprolol-loaded silica sample, and it causes up to 1.6 times decrease of initial release rate with respect to materials without the fatty alcohol. This effect does not depend of carrier pore arrangement, being noticed for both hexagonal MCM-41 and cubic KIT-5 mesoporous silica. The toxicity of tetradecanol-containing materials was evaluated by formazan-based viability assay on Opossum kidney epithelial cell line, and no significant toxicity was observed.

摘要

介孔硅材料是很有前途的药物传递系统的纳米载体。尽管有许多控制药物释放动力学的策略,但这些策略必须根据具体情况进行反复试验和调整。在这里,我们通过添加疏水性赋形剂十四醇来探索调整亲水性、水溶性治疗剂从介孔硅中释放动力学的可能性。在 37°C 下,在磷酸盐缓冲溶液(pH 7.4)中进行的体外药物释放实验表明,十四醇的添加导致药物释放动力学更慢,这与存在液态脂肪醇界面层有关。该层的质量是载有美托洛尔的硅样品的 11-23wt.%,与不含脂肪醇的材料相比,初始释放速率降低了 1.6 倍。这种效应不依赖于载体孔的排列,在六方介孔 MCM-41 和立方介孔 KIT-5 硅中都有注意到。通过对负鼠肾上皮细胞系进行基于甲臜的活力测定评估了含有十四醇的材料的毒性,没有观察到明显的毒性。

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