Institut de Chimie et des Matériaux Paris-Est, UMR 7182 CNRS-Université Paris-Est Créteil, 94320 Thiais, France.
Institute of Particle Technology, Clausthal University of Technology, 38678 Clausthal Zellerfeld, Germany.
Int J Pharm. 2020 Nov 30;590:119930. doi: 10.1016/j.ijpharm.2020.119930. Epub 2020 Sep 30.
Large-pore mesoporous silica (LPMS) microspheres with tunable pore size have received intensive interest in the field of drug delivery due to their high storage capacity and fast delivery rate of drugs. In this work, a facile salt-assisted spray-drying method has been developed to fabricate LPMS microspheres using continuous spray-drying of simple inorganic salts as pore templates and colloidal SiO nanoparticles as building blocks, followed by washing with water to remove the templates. More importantly, the porosity of the LPMS microspheres can be finely tuned by adjusting the furnace temperature and relative concentration of the salt to SiO, which could lead to optimal pharmaceutical outcomes. Then, the biological roles of these LPMS microspheres were evaluated in antibacterial and cancer therapy. In this regard, rhodamine b as a probe was initially loaded inside the LPMS microspheres. The obtained particles not only showed high entrapment efficiency (up to 30%) and a pH-responsive drug release but also presented pore-size-controlled drug release performance. Then, in vitro antibacterial activities of multiple antibiotics, namely nalidixic acid, chloramphenicol, and ciprofloxacin, loaded in the LPMS particles were investigated against two pathogenic bacteria, Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive). The results indicated bacterial inhibition up to 70% and 20% in less than 2 h for Escherichia coli and Staphylococcus aureus, respectively. This inhibition of bacterial growth was accompanied by no bacterial regrowth within 30 h. Finally, the versatility of LPMS microspheres as drug carriers in pancreatic cancer treatment was explored. In this regard, a pro-apoptotic NCL antagonist agent (N6L) as an antitumor agent was successfully loaded onto LPMS microspheres. Interestingly, the resulting particles showed pore-size-dependent anticancer activity with inhibition of cancer cell growth up to 60%.
具有可调节孔径的大孔介孔硅（LPMS）微球由于其对药物的高存储容量和快速释放率，在药物输送领域引起了广泛关注。在这项工作中，开发了一种简便的盐辅助喷雾干燥法，使用连续喷雾干燥简单的无机盐作为孔模板和胶体 SiO2 纳米粒子作为构建块来制备 LPMS 微球，然后用水洗涤以去除模板。更重要的是，通过调整炉温和盐与 SiO2 的相对浓度，可以精细调节 LPMS 微球的多孔性，从而获得最佳的药物效果。然后，评估了这些 LPMS 微球在抗菌和癌症治疗中的生物学作用。在这方面，最初将罗丹明 B 作为探针加载到 LPMS 微球内。所得颗粒不仅表现出高包封效率（高达 30%）和 pH 响应性药物释放，而且还表现出孔径控制的药物释放性能。然后，研究了负载在 LPMS 颗粒中的多种抗生素，即萘啶酸、氯霉素和环丙沙星，对两种致病菌大肠杆菌（革兰氏阴性）和金黄色葡萄球菌（革兰氏阳性）的体外抗菌活性。结果表明，大肠杆菌和金黄色葡萄球菌在不到 2 小时内的抑菌率分别达到 70%和 20%。这种细菌生长的抑制伴随着 30 小时内没有细菌再生长。最后，探索了 LPMS 微球作为胰腺癌治疗中药物载体的多功能性。在这方面，成功地将一种促凋亡 NCL 拮抗剂（N6L）作为抗肿瘤剂加载到 LPMS 微球上。有趣的是，所得颗粒表现出孔径依赖性的抗癌活性，对癌细胞生长的抑制率高达 60%。
