Chemical Engineering Department, Faculty of Engineering, Ferdowsi University of Mashhad, Iran.
Chemical Engineering Department, Faculty of Engineering, Ferdowsi University of Mashhad, Iran.
Colloids Surf B Biointerfaces. 2021 Jun;202:111691. doi: 10.1016/j.colsurfb.2021.111691. Epub 2021 Mar 13.
In this paper, the salt-assisted chitosan nanoparticles (CS NPs) containing metronidazole (MTZ) were prepared using the ionic gelation technique in the presence of NaCl. The effect of different concentrations of NaCl on particle size, zeta potential, polydispersity index (PDI), and entrapment efficiency (EE %) was investigated. Also, the stability of MTZ-loaded CS NPs in the absence/presence of NaCl was evaluated over a 6-month storage period. Furthermore, drug release at pH = 7.4 was examined and the corresponding mechanism was explored. Finally, the time-kill assay of free MTZ and salt-assisted MTZ-loaded CS NPs against Bacteroides fragilis was performed by applying the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). It was found that in the presence of 20 mM NaCl, the optimum NPs can be achieved with the particle size of 284 nm, PDI of 0.099, EE% of 57.4 %, and zeta potential of +46.32 mV. More stability of salt-assisted nanoparticles, as well as lower size enhancement versus time, were observed due to higher surface charge density calculated using the Gouy-Chapman theory. The in-vitro drug release profiles demonstrated a more controlled drug release of MTZ from CS NPs compared to free MTZ, because of the shrinkage properties of CS at high pH. The kinetic modeling of drug release approved the Fickian diffusion of drug based on the Korsmeyer-Peppas model. The time-kill plots confirmed the higher antibacterial activity of salt-assisted MZ-loaded CS NPs compared to the free MTZ against B. fragilis bacterium. In conclusion, the salt-assisted MTZ-loaded CS NPs prepared in the presence of a proper concentration of NaCl, can be an acceptable nanoparticle form for designing MTZ drug delivery systems.
本文采用离子凝胶技术，在 NaCl 存在的条件下制备了载甲硝唑（MTZ）的壳聚糖纳米粒子（CS NPs）。考察了不同浓度 NaCl 对粒径、Zeta 电位、多分散指数（PDI）和包封效率（EE%）的影响。还评估了载 MTZ 的 CS NPs 在无/有 NaCl 存在的情况下在 6 个月的储存期内的稳定性。进一步研究了在 pH = 7.4 下的药物释放情况，并探讨了相应的机制。最后，通过应用最低抑菌浓度（MIC）和最低杀菌浓度（MBC），对游离 MTZ 和载盐 MTZ 的 CS NPs 对脆弱拟杆菌的时间杀伤试验进行了研究。结果发现，在存在 20 mM NaCl 的情况下，可以获得粒径为 284nm、PDI 为 0.099、EE%为 57.4%、Zeta 电位为+46.32mV 的最佳 NPs。由于使用 Gouy-Chapman 理论计算得到的表面电荷密度更高，因此载盐纳米粒子的稳定性更高，且随着时间的推移粒径增大的程度更小。体外药物释放结果表明，由于 CS 在高 pH 下的收缩特性，与游离 MTZ 相比，MTZ 从 CS NPs 中的药物释放更具可控性。药物释放的动力学模型证实了基于 Korsmeyer-Peppas 模型的药物 Fickian 扩散。时间杀伤图证实了载盐 MTZ 的 CS NPs 对脆弱拟杆菌的抗菌活性高于游离 MTZ。总之，在适当浓度的 NaCl 存在下制备的载盐 MTZ 的 CS NPs，可以作为设计 MTZ 药物传递系统的一种可接受的纳米颗粒形式。
