School of Chemical Engineering, The University of Adelaide, Adelaide, SA 5005, Australia.
Int J Pharm. 2013 Feb 25;443(1-2):230-41. doi: 10.1016/j.ijpharm.2012.12.012. Epub 2012 Dec 31.
Diatomaceous earth (DE), or diatomite silica microparticles originated from fossilized diatoms are a potential substitute for its silica-based synthetic counterparts to address limitations in conventional drug delivery. This study presents the impact of engineered surface chemistry of DE microparticles on their drug loading and release properties. Surface modifications with four silanes, including 3-aminopropyltriethoxy silane (APTES), methoxy-poly-(ethylene-glycol)-silane (mPEG-silane), 7-octadecyltrichlorosilane (OTS), 3-(glycidyloxypropyl)trimethoxysilane (GPTMS) and two phosphonic acids, namely 2-carboxyethyl-phosphonic acid (2 CEPA) and 16-phosphono-hexadecanoic acid (16 PHA) were explored in order to tune drug loading and release characteristics of water insoluble (indomethacin) and water soluble drugs (gentamicin). Successful grafting of these functional groups with different interfacial properties was confirmed using X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Thermogravimetric analysis (TGA) was applied to determine the amount of loaded drugs and UV-spectrophotometry to analyse in vitro drug release from modified DE microparticles. Differences in drug release time (13-26 days) and loading capacity (14-24%) were observed depending on functional groups on the surface of DE microparticles. It was found that hydrophilic surfaces, due to the presence of polar carboxyl, amine or hydrolyzed epoxy group, favor extended release of indomethacin, while the hydrophobic DE surface modified by organic hydrocarbons gives a better sustained release profile for gentamicin. This work demonstrates that by changing surface functionalities on DE microparticles, it is possible to tune their drug loading and release characteristics for both hydrophobic and hydrophilic drugs and therefore achieve optimal drug delivery performance.
硅藻土（DE）或硅藻化石起源的硅微粉是一种潜在的替代品，以解决传统药物输送中的限制。本研究探讨了 DE 微粉的工程表面化学对其药物负载和释放性能的影响。用四种硅烷对其进行表面修饰，包括 3-氨丙基三乙氧基硅烷（APTES）、甲氧基-聚（乙二醇）-硅烷（mPEG-硅烷）、十八烷基三氯硅烷（OTS）、3-（缩水甘油氧基）丙基三甲氧基硅烷（GPTMS）和两种膦酸，即 2-羧乙基膦酸（2-CEPA）和 16-磷酰基十六烷酸（16-PHA），以调节水不溶性（吲哚美辛）和水溶性药物（庆大霉素）的负载和释放特性。使用 X 射线光电子能谱（XPS）和傅里叶变换红外光谱（FTIR）证实了这些具有不同界面性能的官能团的成功接枝。热重分析（TGA）用于确定负载药物的量，而紫外分光光度法用于分析改性 DE 微粉中药物的体外释放。根据 DE 微粉表面的官能团不同，观察到药物释放时间（13-26 天）和负载能力（14-24%）的差异。结果发现，亲水表面由于存在极性羧基、胺基或水解的环氧基，有利于吲哚美辛的延长释放，而用有机烃改性的疏水性 DE 表面则有利于庆大霉素的持续释放。这项工作表明，通过改变 DE 微粉的表面官能团，可以调节其对疏水性和亲水性药物的负载和释放特性，从而实现最佳的药物输送性能。
