生物活性

• 描述Natamycin is an important polyene macrolide antifungal agent produced by several Streptomyces strains and is widely used as a food preservative and fungicide in food, medicinal and veterinary products^[3]. Natamycin treatment was associated with significantly better clinical and microbiological outcomes than voriconazole treatment for smear-positive filamentous fungal keratitis, with much of the difference attributable to improved results in Fusarium cases^[4]. The interaction of natamycin-azithromycin combination against 60 ocular fungal isolates was tested in vitro. The combination produced 100% synergistic interactions when natamycin was added to azithromycin 20, 40, and 50 μg/ml against Aspergillus flavus species complex (AFSC) isolates and to azithromycin 50 μg/ml against Fusarium solani species complex isolates. Addition of 50 μg/ml azithromycin enhanced natamycin's effect against AFSC isolates by reducing natamycin MIC90 from 64 to 0.031 μg/ml. No antagonism was observed^[5]. NAT-SLNs (Natamycin solid lipid nanoparticles) were found to be non-irritating to corneal tissue. NAT-SLNs had a prolonged drug release rate, that improved corneal penetration, and increased antifungal activity without cytotoxic effects on corneal tissues. NAT-SLNs represent a promising ocular delivery system for treatment of deep corneal keratitis^[6].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00997035	Corneal Ulcer ... more >> Eye Infections, Fungal Collapse <<	Phase 3	Completed	-	United States, California ... more >> Proctor Foundation, UCSF San Francisco, California, United States, 94143 India Aravind Eye Hospital Coimbatore, Tamil Nadu, India Aravind Eye Hospitals Madurai, Tamil Nadu, India Aravind Eye Hospital Pondicherry, Tamil Nadu, India Aravind Eye Hospital Tirunelveli, Tamil Nadu, India Nepal Bharatpur Eye Hospital Bharatpur, Chitwan, Nepal Lumbini Eye Institute Bhairahawa, Lumbini, Nepal Collapse <<
  NCT02865876	Keratitis	Phase 3	Unknown	March 2017	Mexico ... more >> Instituto de Oftalmologia Conde de Valenciana Recruiting Mexico City, Mexico, 06800 Contact: Lucero Pedro-aguilar, MD       lu.pedroaguilar@gmail.com    Contact: Enrique Graue-Hernandez, MD, MSc       egraueh@gmail.com Collapse <<
  NCT00516399	Fungal Keratitis	Phase 3	Terminated(The DSMC decided it... more >> appeared futile to attempt to demonstrate non-inferiority of povidone-iodine to Natamycin.) Collapse <<	-	-

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• 参考文献

• [1] te Welscher YM, Jones L,et al. Natamycin inhibits vacuole fusion at the priming phase via a specific interaction with ergosterol. Antimicrob Agents Chemother. 2010 Jun;54(6):2618-25. doi: 10.1128/AAC.01794-09. Epub 2010 Apr 12.

  [2] te Welscher YM, ten Napel HH, et al. Natamycin blocks fungal growth by binding specifically to ergosterol without permeabilizing the membrane. J Biol Chem. 2008 Mar 7;283(10):6393-401.

  [3] Wu H, Liu W, Dong D, Li J, Zhang D, Lu C. SlnM gene overexpression with different promoters on natamycin production in Streptomyces lydicus A02. J Ind Microbiol Biotechnol. 2014;41(1):163‐172

  [4] Prajna NV, Krishnan T, Mascarenhas J, et al. The mycotic ulcer treatment trial: a randomized trial comparing natamycin vs voriconazole. JAMA Ophthalmol. 2013;131(4):422‐429

  [5] Guo H, Zhou L, He Y, Gao C, Han L, Xu Y. Natamycin and Azithromycin Are Synergistic In Vitro against Ocular Pathogenic Aspergillus flavus Species Complex and Fusarium solani Species Complex Isolates. Antimicrob Agents Chemother. 2018;62(7):e00077-18. Published 2018 Jun 26

  [6] Khames A, Khaleel MA, El-Badawy MF, El-Nezhawy AOH. Natamycin solid lipid nanoparticles - sustained ocular delivery system of higher corneal penetration against deep fungal keratitis: preparation and optimization. Int J Nanomedicine. 2019;14:2515‐2531

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