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仿生工程化两性霉素 B 纳米聚集体规避了毒性限制,可治疗实验动物的系统性真菌感染。

Biomimetically engineered Amphotericin B nano-aggregates circumvent toxicity constraints and treat systemic fungal infection in experimental animals.

机构信息

Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.

Department of Applied Physics, Aligarh Muslim University, Aligarh, India.

出版信息

Sci Rep. 2017 Sep 19;7(1):11873. doi: 10.1038/s41598-017-11847-0.

DOI:10.1038/s41598-017-11847-0
PMID:28928478
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5605718/
Abstract

Biomimetic synthesis of nanoparticles offers a convenient and bio friendly approach to fabricate complex structures with sub-nanometer precision from simple precursor components. In the present study, we have synthesized nanoparticles of Amphotericin B (AmB), a potent antifungal agent, using Aloe vera leaf extract. The synthesis of AmB nano-assemblies (AmB-NAs) was established employing spectro-photometric and electron microscopic studies, while their crystalline nature was established by X-ray diffraction. AmB-nano-formulation showed much higher stability in both phosphate buffer saline and serum and exhibit sustained release of parent drug over an extended time period. The as-synthesized AmB-NA possessed significantly less haemolysis as well as nephrotoxicity in the host at par with Ambisome, a liposomized AmB formulation. Interestingly, the AmB-NAs were more effective in killing various fungal pathogens including Candida spp. and evoked less drug related toxic manifestations in the host as compared to free form of the drug. The data of the present study suggest that biomimetically synthesized AmB-NA circumvent toxicity issues and offer a promising approach to eliminate systemic fungal infections in Balb/C mice.

摘要

仿生合成纳米粒子为从简单的前体成分制造具有亚纳米精度的复杂结构提供了一种方便且对生物友好的方法。在本研究中,我们使用库拉索芦荟叶提取物合成了两性霉素 B(AmB),一种有效的抗真菌药物的纳米粒子。通过光谱光度法和电子显微镜研究建立了 AmB 纳米组装体(AmB-NAs)的合成,而 X 射线衍射则确定了其晶体性质。AmB-纳米制剂在磷酸盐缓冲盐水和血清中均表现出更高的稳定性,并在延长的时间内持续释放母体药物。与脂质体化的 AmB 制剂 Ambisome 相比,所合成的 AmB-NA 在宿主中具有明显更低的溶血和肾毒性。有趣的是,与游离药物相比,AmB-NAs 对各种真菌病原体(包括念珠菌属)的杀灭作用更强,并且在宿主中引起的药物相关毒性表现更少。本研究的数据表明,仿生合成的 AmB-NA 规避了毒性问题,并为消除 Balb/C 小鼠的全身性真菌感染提供了一种有前途的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2c/5605718/e2d38f6ed727/41598_2017_11847_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2c/5605718/45291d9d435f/41598_2017_11847_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2c/5605718/0a323a5ac50d/41598_2017_11847_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2c/5605718/9e93e74db075/41598_2017_11847_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2c/5605718/0418372e5c18/41598_2017_11847_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2c/5605718/31d4a1825134/41598_2017_11847_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2c/5605718/e2d38f6ed727/41598_2017_11847_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2c/5605718/45291d9d435f/41598_2017_11847_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2c/5605718/0a323a5ac50d/41598_2017_11847_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2c/5605718/9e93e74db075/41598_2017_11847_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2c/5605718/0418372e5c18/41598_2017_11847_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2c/5605718/31d4a1825134/41598_2017_11847_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c2c/5605718/e2d38f6ed727/41598_2017_11847_Fig6_HTML.jpg

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