Choi Youngjin, Lee Jung Eun, Lee Jung Heon, Jeong Ji Hoon, Kim Jaeyun
†School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
‡School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Langmuir. 2015 Jun 16;31(23):6457-62. doi: 10.1021/acs.langmuir.5b01316. Epub 2015 Jun 4.
Mesoporous silica has received considerable attention as a drug delivery vehicle because of its large surface area and large pore volume for loading drugs and large biomolecules. Recently, mesoporous silica microparticles have shown potential as a three-dimensional vaccine platform for modulating dendritic cells via spontaneous assembly of microparticles in a specific region after subcutaneous injection. For further in vivo applications, the biodegradation behavior of mesoporous silica microparticles must be studied and known. Until now, most biodegradation studies have focused on mesoporous silica nanoparticles (MSNs); here, we report the biodegradation of hexagonally ordered mesoporous silica, SBA-15, with micrometer-sized lengths (∼32 μm with a high aspect ratio). The degradation of SBA-15 microparticles was investigated in simulated body fluid (SBF) and in mice by analyzing the structural change over time. SBA-15 microparticles were found to degrade in SBF and in vivo. The erosion of SBA-15 under biological conditions led to a loss of the hysteresis loop in the nitrogen adsorption/desorption isotherm and fingerprint peaks in small-angle X-ray scattering, specifically indicating a degradation of ordered mesoporous structure. Via comparison to previous results of degradation of MSNs in SBF, SBA-15 microparticles degraded faster than MCM-41 nanoparticles presumably because SBA-15 microparticles have a pore size (∼8 nm) and a pore volume larger than those of MCM-41 mesoporous silica. The surface functional groups, the residual amounts of organic templates, and the hydrothermal treatment during the synthesis could affect the rate of degradation of SBA-15. In in vivo testing, previous studies focused on the evaluation of toxicity of mesoporous silica particles in various organs. In contrast, we studied the change in the physical properties of SBA-15 microparticles depending on the duration after subcutaneous injection. The pristine SBA-15 microparticles injected into mice subcutaneously slowly degraded over time and lost ordered structure after 3 days. These findings represent the possible in vivo use of microsized mesoporous silica for drug delivery or vaccine platform after local injection.
介孔二氧化硅因其具有较大的表面积、较大的药物和大分子负载孔体积,作为一种药物递送载体受到了广泛关注。最近,介孔二氧化硅微粒已显示出作为三维疫苗平台的潜力,可通过皮下注射后微粒在特定区域的自发组装来调节树突状细胞。为了进一步用于体内应用,必须研究并了解介孔二氧化硅微粒的生物降解行为。到目前为止,大多数生物降解研究都集中在介孔二氧化硅纳米颗粒(MSNs)上;在此,我们报告了具有微米级长度(约32μm,高纵横比)的六方有序介孔二氧化硅SBA - 15的生物降解情况。通过分析随时间的结构变化,研究了SBA - 15微粒在模拟体液(SBF)和小鼠体内的降解情况。发现SBA - 15微粒在SBF和体内均会降解。SBA - 15在生物条件下的侵蚀导致氮吸附/解吸等温线中的滞后环消失以及小角X射线散射中的指纹峰消失,具体表明有序介孔结构发生了降解。通过与先前关于MSNs在SBF中降解的结果进行比较,SBA - 15微粒的降解速度比MCM - 41纳米颗粒快,这可能是因为SBA - 15微粒的孔径(约8nm)和孔体积比MCM - 41介孔二氧化硅大。表面官能团、有机模板的残留量以及合成过程中的水热处理可能会影响SBA - 15的降解速率。在体内测试中,先前的研究集中在评估介孔二氧化硅颗粒在各个器官中的毒性。相比之下,我们研究了皮下注射后不同时间SBA - 15微粒物理性质的变化。皮下注射到小鼠体内的原始SBA - 15微粒会随着时间缓慢降解,并在3天后失去有序结构。这些发现表明微米级介孔二氧化硅在局部注射后用于药物递送或疫苗平台的体内应用具有可能性。