Ejaz Sadaf, Ejaz Saima, Shahid Ramla, Noor Tayyaba, Shabbir Saima, Imran Muhammad
Department of Biosciences, Faculty of Sciences, COMSATS University Islamabad (CUI), Park Road, Islamabad, Pakistan.
Research Centre for Modelling and Simulation (RCMS), National University of Science and Technology (NUST), Islamabad, Pakistan.
Int J Biol Macromol. 2022 Apr 15;204:540-554. doi: 10.1016/j.ijbiomac.2022.02.039. Epub 2022 Feb 11.
With the apparent stagnation in the antibiotic discovery and the propagation of multidrug resistance, Helicobacter pylori associated gastric infections are hard to eradicate. In pursuance of alternative medicines, in this study, covalent modification of chitosan (CS) polymer with curcumin (Cur) was accomplished. Proton Nuclear Magnetic Resonance and Fourier Transform Infrared spectroscopy elucidated the covalent interaction between Cur and CS with characteristic peak of imine functional group (C=N). Scanning Electron Microscopy provided visual proof for surface topology, while size and zeta potential values further affirmed the development of curcumin functionalized chitosan nanosystems (Cur-FCNS). The complexation efficiency of CS with Cur was found as 70 ± 3% at an optimal ratio of 5:1 for CS and Cur, respectively. Cur-FCNS developed with ionic gelation and ultrasonication method demonstrated synergistic anti-H. pylori activity in growth-kinetics and anti-biofilm assays, which was superior to free Cur and even chitosan nanosystems. Under simulated gastric conditions, Cur-FCNS revealed cumulative-release of only 16 ± 0.8% till 40 h, which indicated its improved stability to interact with H. pylori. In silico findings affirmed high binding affinity of Cur-FCNS with multiple bacterial virulence factors. Thus, our results affirmed the exceptional potential of Cur-FCNS as next-generation alternative-medicine to treat resistant H. pylori.
随着抗生素发现的明显停滞以及多重耐药性的传播，幽门螺杆菌相关的胃部感染难以根除。为了寻找替代药物，在本研究中，实现了姜黄素（Cur）对壳聚糖（CS）聚合物的共价修饰。质子核磁共振和傅里叶变换红外光谱通过亚胺官能团（C=N）的特征峰阐明了Cur与CS之间的共价相互作用。扫描电子显微镜提供了表面拓扑结构的视觉证据，而尺寸和zeta电位值进一步证实了姜黄素功能化壳聚糖纳米系统（Cur-FCNS）的形成。在CS与Cur的最佳比例分别为5:1时，发现CS与Cur的络合效率为70±3%。采用离子凝胶法和超声法制备的Cur-FCNS在生长动力学和抗生物膜试验中表现出协同抗幽门螺杆菌活性，优于游离Cur甚至壳聚糖纳米系统。在模拟胃条件下，Cur-FCNS在40小时内仅累积释放16±0.8%，这表明其与幽门螺杆菌相互作用时稳定性增强。计算机模拟结果证实Cur-FCNS与多种细菌毒力因子具有高结合亲和力。因此，我们的结果证实了Cur-FCNS作为治疗耐药幽门螺杆菌的下一代替代药物具有巨大潜力。
