Björk Emma M, Baumann Bernhard, Hausladen Florian, Wittig Rainer, Lindén Mika
Institute for Inorganic Chemistry II, University of Ulm Albert-Einstein-Allee 11 890 81 Ulm Germany
Nanostructured Materials, Department of Physics, Chemistry and Biology (IFM), Linköping University 581 83 Linköping Sweden
RSC Adv. 2019 Jun 5;9(31):17745-17753. doi: 10.1039/c9ra02823d. eCollection 2019 Jun 4.
Spatially and temporally controlled drug delivery is important for implant and tissue engineering applications, as the efficacy and bioavailability of the drug can be enhanced, and can also allow for drugging stem cells at different stages of development. Long-term drug delivery over weeks to months is however difficult to achieve, and coating of 3D surfaces or creating patterned surfaces is a challenge using coating techniques like spin- and dip-coating. In this study, mesoporous films consisting of SBA-15 particles grown onto silicon wafers using wet processing were evaluated as a scaffold for drug delivery. Films with various particle sizes (100-900 nm) and hence thicknesses were grown onto trichloro(octadecyl)silane-functionalized silicon wafers using a direct growth method. Precise patterning of the areas for film growth could be obtained by local removal of the OTS functionalization through laser ablation. The films were incubated with the drug model 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO), and murine myoblast cells (C2C12 cells) were seeded onto films with different particle sizes. Confocal laser scanning microscopy (CLSM) was used to study the cell growth, and a vinculin-mediated adherence of C2C12 cells on all films was verified. The successful loading of DiO into the films was confirmed by UV-vis and CLSM. It was observed that the drugs did not desorb from the particles during 24 hours in cell culture. During adherent growth on the films for 4 h, small amounts of DiO and separate particles were observed inside single cells. After 24 h, a larger number of particles and a strong DiO signal were recorded in the cells, indicating a particle mediated drug uptake. The vast majority of the DiO-loaded particles remained attached to the substrate also after 24 h of incubation, making the films attractive as longer-term reservoirs for drugs on medical implants.
对于植入和组织工程应用而言，空间和时间可控的药物递送非常重要，因为这样可以提高药物的疗效和生物利用度，还能在干细胞发育的不同阶段对其进行药物处理。然而，要实现长达数周甚至数月的长期药物递送却很困难，而且使用旋涂和浸涂等涂层技术对三维表面进行涂层或制造图案化表面是一项挑战。在本研究中，评估了通过湿法工艺在硅片上生长的由SBA - 15颗粒组成的介孔薄膜作为药物递送的支架。使用直接生长法将具有各种粒径（100 - 900 nm）以及相应厚度的薄膜生长在三氯（十八烷基）硅烷功能化的硅片上。通过激光烧蚀局部去除OTS功能化，可以实现薄膜生长区域的精确图案化。将这些薄膜与药物模型高氯酸3,3'-二辛基氧杂羰花青（DiO）一起孵育，并将小鼠成肌细胞（C2C12细胞）接种到具有不同粒径的薄膜上。使用共聚焦激光扫描显微镜（CLSM）研究细胞生长情况，并验证了C2C12细胞在所有薄膜上通过纽蛋白介导的黏附。通过紫外可见光谱和CLSM证实了DiO成功加载到薄膜中。观察到在细胞培养的24小时内，药物没有从颗粒上解吸。在薄膜上贴壁生长4小时后，在单个细胞内观察到少量的DiO和分离的颗粒。24小时后，细胞内记录到大量颗粒和强烈的DiO信号，表明存在颗粒介导的药物摄取。即使在孵育24小时后，绝大多数负载DiO的颗粒仍附着在基质上，这使得这些薄膜作为医用植入物上药物的长期储存库具有吸引力。
