Abstract:
Acanthamoeba castellanii causes granulomatous amoebic encephalitis, an uncommon but severe brain infection and sight-threatening Acanthamoeba keratitis. Most of the currently used anti-amoebic treatments are not always effective, due to persistence of the cyst stage, and recurrence can occur. Here in this study we synthesize cinnamic acid and lactobionic acid-based magnetic nanoparticles (MNPs) using co-precipitation technique. These nanoformulations were characterized by Fourier transform infrared spectroscopy and Atomic form microscopy. The drugs alone (Hesperidin, Curcumin and Amphotericin B), magnetic NPs alone, and drug-loaded nano-formulations were evaluated at a concentration of 100 μg/mL for antiamoebic activity against a clinical isolate of A. castellanii. Amoebicidal assays revealed that drugs and conjugation of drugs and NPs further enhanced amoebicidal effects of drug-loaded nanoformulations. Drugs and drug-loaded nanoformulations inhibited both encystation and excystation of amoebae. In addition, drugs and drug-loaded nanoformulations inhibited parasite binding capability to the host cells. Neither drugs nor drug-loaded nanoformulations showed cytotoxic effects against host cells and considerably reduced parasite-mediated host cell death. Overall, these findings imply that conjugation of medically approved drugs with MNPs produce potent anti-Acanthamoebic effects, which could eventually lead to the development of therapeutic medications.
摘要:
卡氏棘阿米巴引起肉芽肿性阿米巴性脑炎,罕见但严重的脑部感染和危及视力的棘阿米巴角膜炎。大多数目前使用的抗阿米巴治疗并不总是有效的,由于囊肿期的持续,并且可以复发。在这项研究中,我们使用共沉淀技术合成了肉桂酸和乳糖酸基磁性纳米颗粒(MNPs)。通过傅里叶变换红外光谱和原子形式显微镜表征这些纳米制剂。单独的药物(橙皮苷,姜黄素和两性霉素B),只有磁性NP,和负载药物的纳米制剂在100μg/mL的浓度下评估针对卡氏A.castellanii临床分离株的抗阿米巴活性。杀菌试验揭示了药物和药物与NP的结合进一步增强了载药纳米制剂的杀菌效果。药物和载药纳米制剂抑制变形虫的包壳和脱落。此外,药物和载药纳米制剂抑制寄生虫与宿主细胞的结合能力。药物或载药纳米制剂均未显示出对宿主细胞的细胞毒性作用,并且大大减少了寄生虫介导的宿主细胞死亡。总的来说,这些发现暗示医学批准的药物与MNPs的结合产生有效的抗棘阿米巴作用,这最终可能导致治疗药物的发展。