Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan 81746-73441, Iran.
Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan 81746-73441, Iran.
Int J Pharm. 2018 Feb 15;537(1-2):148-161. doi: 10.1016/j.ijpharm.2017.12.039. Epub 2017 Dec 24.
Polymyxin B is a polycationic antibiotic used as the last line treatment against antibiotic-resistant Gram negative bacteria. However, application of polymyxin B is limited because of its toxicity effects. Herein, we used bare and surface modified mesoporous silica nanoparticles (MSNs) with an average diameter of 72.29 ± 8.17 nm as adsorbent for polymyxin B to improve its therapeutic properties. The polymyxin B adsorption onto MSN surfaces was explained as a function of pH, type of buffer and surface charge of nanoparticles, according to the ζ-potential of silica nanoparticles and adsorption kinetics results. The highest value of the adsorption capacity (about 401 ± 15.38 mg polymyxin B/ g silica nanoparticles) was obtained for the bare nanoparticles in Tris buffer, pH 9. Release profiles of polymyxin B showed a sustained release pattern, fitting Power law and Hill models. The antibiotic molecules-loaded nanoparticles showed enhanced antibacterial activity compared to free antibiotic against different Gram negative bacteria. Biocompatibility evaluation results revealed that loading of polymyxin B onto MSNs can decrease the cytotoxicity effects of the drug by reducing ROS generation. Our results suggest that formulation of drugs by adsorption onto MSNs may offer a way forward to overcome the adverse effects of some antibiotics such as polymyxin B without compromising their antimicrobial properties.
多粘菌素 B 是一种多阳离子抗生素，用作对抗抗药性革兰氏阴性菌的最后一线治疗药物。然而，由于其毒性作用，多粘菌素 B 的应用受到限制。在此，我们使用平均直径为 72.29±8.17nm 的裸和表面改性介孔硅纳米粒子（MSNs）作为多粘菌素 B 的吸附剂，以改善其治疗性能。根据硅胶纳米粒子的 ζ-电位和吸附动力学结果，多粘菌素 B 在 MSN 表面上的吸附被解释为 pH、缓冲液类型和纳米粒子表面电荷的函数。在 pH 9 的 Tris 缓冲液中，裸纳米粒子的吸附容量（约 401±15.38mg 多粘菌素 B/g 硅胶纳米粒子）最高。多粘菌素 B 的释放曲线呈持续释放模式，符合幂律和 Hill 模型。与游离抗生素相比，载有抗生素分子的纳米粒子对不同的革兰氏阴性菌表现出增强的抗菌活性。细胞相容性评价结果表明，通过减少 ROS 的产生，将多粘菌素 B 负载到 MSNs 上可以降低药物的细胞毒性作用。我们的研究结果表明，通过吸附到 MSNs 上对药物进行制剂可以克服一些抗生素（如多粘菌素 B）的不良反应，而不会损害其抗菌性能。
