Colon targeted drug delivery is highly relevant not only to treat colonic local diseases but also for systemic therapies. Mesoporous silica nanoparticles (MSNs) have been demonstrated as useful systems for controlled drug release given their biocompatibility and the possibility of designing gated systems able to release cargo only upon the presence of certain stimuli. We report herein the preparation of three gated MSNs able to deliver their cargo triggered by different stimuli (redox ambient (S1), enzymatic hydrolysis (S2), and a surfactant or being in contact with cell membrane (S3)) and their performance in solution and in vitro with Caco-2 cells. Safranin O dye was used as a model drug to track cargo fate. Studies of cargo permeability in Caco-2 monolayers demonstrated that intracellular safranin O levels were significantly higher in Caco-2 monolayers when using MSNs compared to those of free dye. Internalization assays indicated that S2 nanoparticles were taken up by cells via endocytosis. S2 nanoparticles were selected for in vivo tests in rats. For in vivo assays, capsules were filled with S2 nanoparticles and coated with Eudragit FS 30 D to target colon. The enteric coated capsule containing the MSNs was able to deliver S2 nanoparticles in colon tissue (first step), and then nanoparticles were able to deliver safranin O inside the colonic cells after the enzymatic stimuli (second step). This resulted in high levels of safranin O in colonic tissue combined with low dye levels in plasma and body tissues. The results suggested that this combination of enzyme-responsive gated MSNs and enteric coated capsules may improve the absorption of drugs in colon to treat local diseases with a reduction of systemic effects.

中文翻译：

---

门控介孔二氧化硅纳米载体用于结肠组织的“两步”靶向系统

结肠靶向药物的递送不仅与治疗结肠局部疾病有关，而且与全身疗法也高度相关。介孔二氧化硅纳米粒子（MSNs）已被证明是用于控制药物释放的有用系统，因为它们具有生物相容性，并且有可能设计出仅在存在某些刺激时才能够释放货物的门控系统。我们在这里报告了三种门控MSN的制备，它们能够通过不同的刺激（氧化还原环境（S1），酶促水解（S2），表面活性剂或与细胞膜接触（S3））触发释放货物。和体外Caco-2细胞。番红O染料被用作跟踪货物命运的模型药物。Caco-2单层货物通透性研究表明，与游离染料相比，使用MSN时Caco-2单层细胞内藏红素O含量显着更高。内部化分析表明，S2纳米颗粒通过细胞吞噬作用被细胞吸收。选择S2纳米颗粒用于大鼠体内测试。为了进行体内测定，将胶囊装满S2纳米颗粒，并用Eudragit FS 30 D包被以靶向结肠。含有MSN的肠溶胶囊能够递送S2结肠组织中的纳米颗粒（第一步），然后纳米颗粒能够在酶促刺激后在结肠细胞内递送番红素O（第二步）。这导致结肠组织中藏红素O含量高，而血浆和身体组织中染料含量低。结果表明，酶促反应门控MSN和肠溶衣胶囊的这种结合可以提高结肠中药物的吸收，从而减少局部疾病，从而治疗局部疾病。