Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
Children's Hospital, University Medical Center of the Johannes-Gutenberg University, Mainz, Germany.
Nanoscale. 2020 Jan 28;12(4):2626-2637. doi: 10.1039/c9nr09879h. Epub 2020 Jan 15.
Immunosuppression with glucocorticoids is a common treatment for autoimmune liver diseases and after liver transplant, which is however associated with severe side-effects. Targeted delivery of glucocorticoids to inflammatory cells, e.g. liver macrophages and Kupffer cells, is a promising approach for minimizing side effects. Herein, we prepare core-shell silica nanocapsules (SiO NCs) via a sol-gel process confined in nanodroplets for targeted delivery of dexamethasone (DXM) for liver immunosuppressive therapy. DXM with concentrations up to 100 mg mL in olive oil are encapsulated while encapsulation efficiency remains over 95% after 15 days. Internalization of NCs by non-parenchymal murine liver cells significantly reduces the release of inflammatory cytokines, indicating an effective suppression of inflammatory response of liver macrophages. Fluorescent and magnetic labeling of the NCs allows for monitoring their intracellular trafficking and biodegradation. Controlled interaction with blood proteins and good colloidal stability in blood plasma are achieved via PEGylation of the NCs. Specific proteins responsible for stealth effect, such as apolipoprotein A-I, apolipoprotein A-IV, and clusterin, are present in large amounts on the PEGylated NCs. In vivo biodistribution investigations prove an efficient accumulation of NCs in the liver, underlining the suitability of the SiO NCs as a dexamethasone carrier for treating inflammatory liver diseases.
免疫抑制治疗中常使用糖皮质激素（如地塞米松）来治疗自身免疫性肝病和肝移植术后排异反应，但同时会引起严重的副作用。将糖皮质激素靶向递送至炎症细胞（如肝巨噬细胞和枯否细胞）是一种降低副作用的有前景的方法。在此，我们通过受限在纳米液滴中的溶胶-凝胶过程制备了核壳型二氧化硅纳米胶囊（SiO NCs），以用于地塞米松（DXM）的靶向递送至肝脏免疫抑制治疗。DXM 在橄榄油中的浓度高达 100 mg mL 时也能被包封，且在 15 天后包封效率仍保持在 95%以上。NCs 被非实质的鼠肝细胞内化，显著减少了炎症细胞因子的释放，表明对肝巨噬细胞炎症反应有有效的抑制作用。NCs 的荧光和磁性标记使其能够监测其细胞内转运和生物降解。通过 NCs 的聚乙二醇化实现了与血液蛋白的可控相互作用和在血浆中的良好胶体稳定性。大量的载脂蛋白 A-I、载脂蛋白 A-IV 和簇蛋白等负责隐形效果的特异性蛋白存在于聚乙二醇化的 NCs 上。体内生物分布研究证明了 NCs 在肝脏中的有效积累，这突出了 SiO NCs 作为治疗炎症性肝病的地塞米松载体的适用性。
