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论铜的物理化学参数和氨基硅烷功能化介孔硅对于羟氯喹释放的重要性。

On the importance of physicochemical parameters of copper and aminosilane functionalized mesoporous silica for hydroxychloroquine release.

机构信息

Adam Mickiewicz University in Poznań, Faculty of Chemistry, Department of Chemical Technology, Uniwersytetu Poznańskiego 8, 61-614 Poznań, Poland.

出版信息

Mater Sci Eng C Mater Biol Appl. 2021 Nov;130:112438. doi: 10.1016/j.msec.2021.112438. Epub 2021 Sep 17.

Abstract

Recently, great attention has been paid to hydroxychloroquine which after promising in vitro studies has been proposed to treat the severe acute respiratory syndrome caused by SARS-CoV-2. The clinical trials have shown that hydroxychloroquine was not as effective as was expected and additionally, several side effects were observed in patients cured with this medicament. In order to reduce them, it is suggested to deliver hydroxychloroquine in a controlled manner. Therefore, in this study non-modified (SBA-15, SBA-16) and modified with copper and aminosilane mesoporous silica materials were applied as novel nanocarriers for hydroxychloroquine. First, pristine and functionalized samples were synthesized and characterized by X-ray diffraction, low-temperature nitrogen sorption, transmission electron microscopy, X-ray photoelectron spectroscopy, infrared spectroscopy, laser diffraction. Then the influence of physicochemical parameters of materials obtained on the adsorption and release processes of hydroxychloroquine was analyzed. The mechanism of hydroxychloroquine binding to non-modified silicas was based on the formation of hydrogen bonds, while in the case of copper and aminosilane functionalized materials the complexes with drug molecules were generated. The release behavior of hydroxychloroquine from silica samples obtained was determined by different factors including pH conditions, textural parameters, surface charge, and presence of surface functional groups. The greatest differences in hydroxychloroquine release profiles between materials were observed at pH 7.2. The amount of drug desorbed from silica decreased in the following order: functionalized SBA-15 (84%) > functionalized SBA-16 (79%) > SBA-15 (59%) > SBA-16 (33%). It proved that a higher amount of drug was released from materials of hexagonal structure.

摘要

最近,人们对羟氯喹给予了极大的关注,在体外研究有了可喜的结果之后,人们提出用它来治疗由 SARS-CoV-2 引起的严重急性呼吸综合征。临床试验表明,羟氯喹的效果并不像预期的那样好,而且在用这种药物治疗的患者中还观察到了一些副作用。为了减少这些副作用,建议以控制的方式给予羟氯喹。因此,在这项研究中,未修饰的(SBA-15、SBA-16)和用铜和氨丙基硅烷修饰的介孔硅材料被用作羟氯喹的新型纳米载体。首先,合成并通过 X 射线衍射、低温氮气吸附、透射电子显微镜、X 射线光电子能谱、红外光谱、激光衍射对原始和功能化的样品进行了表征。然后分析了所获得的材料的物理化学参数对羟氯喹吸附和释放过程的影响。羟氯喹与未修饰的硅材料结合的机制基于氢键的形成,而在铜和氨丙基硅烷功能化材料的情况下,则生成了与药物分子的配合物。通过不同的因素,包括 pH 值条件、结构参数、表面电荷和表面官能团的存在,确定了从获得的硅样品中释放羟氯喹的行为。在 pH 7.2 时,材料之间羟氯喹释放曲线的差异最大。从硅材料上解吸的药物量按以下顺序减少:功能化 SBA-15(84%)>功能化 SBA-16(79%)>SBA-15(59%)>SBA-16(33%)。这证明了具有六方结构的材料释放了更多的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e02a/8445882/9b1bbc78dad7/ga1_lrg.jpg

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