Manandhar Krishna Das, Yadav Thakur Prasad, Prajapati Vijay Kumar, Kumar Subodh, Rai Madhukar, Dube Anuradha, Srivastava Onkar Nath, Sundar Shyam
Infectious Disease Research Laboratory, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India.
J Antimicrob Chemother. 2008 Aug;62(2):376-80. doi: 10.1093/jac/dkn189. Epub 2008 May 2.
The aim of the present study was to compare the efficacy of a nano form of amphotericin B deoxycholate with that of conventional amphotericin B deoxycholate for the treatment of visceral leishmaniasis.
We have formulated nanoparticles (10-20 nM) from amphotericin B deoxycholate (1-2 microM) by applying high-pressure (150 argon) milling homogenization and have tested their efficacy in a J774A cell line and in hamsters. Parasite survival and tissue burden in spleen were evaluated for nano-amphotericin B and conventional amphotericin B. Both nano-amphotericin B and conventional amphotericin B were injected intraperitoneally at 5 mg/kg per day for 5 days.
The inhibition of amastigotes in the splenic tissue with nano-amphotericin B was significantly more than with conventional amphotericin B (92.18% versus 74.57%, P = 0.005). Similarly, the suppression of parasite replication in the spleen was also found to be significant (99.18% versus 97.17%, P = 0.05). In a cytotoxicity test, nano-amphotericin B against the J774A cell line had a CC(50) of 12.67 mg/L in comparison with 10.61 mg/L for amphotericin B, far higher than the doses used for ED(50).
Nanoparticles of amphotericin B had significantly greater efficacy than conventional amphotericin B. This formulation may have a favourable safety profile, and if production costs are low, it may prove to be a feasible alternative to conventional amphotericin B.
本研究旨在比较纳米形式的两性霉素B去氧胆酸盐与传统两性霉素B去氧胆酸盐治疗内脏利什曼病的疗效。
我们通过高压（150氩）研磨均质法，用两性霉素B去氧胆酸盐（1 - 2 microM）制备了纳米颗粒（10 - 20 nM），并在J774A细胞系和仓鼠中测试了它们的疗效。评估了纳米两性霉素B和传统两性霉素B对脾脏中寄生虫存活和组织负荷的影响。纳米两性霉素B和传统两性霉素B均以每天5 mg/kg的剂量腹腔注射，共注射5天。
纳米两性霉素B对脾脏组织中无鞭毛体的抑制作用明显大于传统两性霉素B（92.18%对74.57%，P = 0.005）。同样，脾脏中寄生虫复制的抑制也很显著（99.18%对97.17%，P = 0.05）。在细胞毒性试验中，纳米两性霉素B对J774A细胞系的CC(50)为12.67 mg/L，而两性霉素B为10.61 mg/L，远高于用于ED(50)的剂量。
两性霉素B纳米颗粒的疗效明显高于传统两性霉素B。这种制剂可能具有良好的安全性，如果生产成本低，可能被证明是传统两性霉素B的可行替代品。
