Therapeutic efficacy and safety of nano-silver membrane with voriconazole for Aspergillus fumigatus keratitis after topical application

Authors: Zhong Jing,  Yuan Jin,  Jiang Gangbiao,  Chen Guopu,  Sun Yifang,  Chen Ling,  Deng Yuqing
DOI: 10.3760/cma.j.issn.2095-0160.2015.05.006
Published 2015-05-10
Cite as Chin J Exp Ophthalmol, 2015,33(5): 412-418.

Abstract                              [Download PDF] [Read Full Text]


Voriconazole is the traditionally used antifungal agent, but its ophthalmic form is unsatisfactory.A novel ophthalmic drug delivery system with biomedical devices may be of promising for the prognosis of fungal keratitis.


This study was to investigate the sustained release, therapeutic effect and biocompatibility of effect and quaternized chitosan functionalized with carboxylated graphene and nano-silver and voriconazole (CS-ETA/Ag/GO/Vor) for fungal keratitis.


This study complied with the Regulations for the Administration of Affair Concerning Experimental Animals of State Science and Technology Commission.Two hundred and ten SPF female C57BL/6 mice were selected with the age 6-8 weeks for the biocompatibility experiment (30 mice) and therapeutic observation of CS-ETA/Ag/GO/Vor (180 mice). CS-ETA/Ag/GO and CS-ETA/Ag/GO/Vor were attached on the normal corneas of mice and compared with the normal mice to assess the histopathological changes.Aspergillus fumigatus-infected mouse models were established in the left eyes of 180 mice by intrastromally injection of 2.0 μl Aspergillus fumigatus suspension with the density of 5×107 CFU/ml, then the mice were randomized into the model control group, CS-ETA/Ag/GO group and CS-ETA/Ag/GO/Vor group, and the corresponding membrane were attached the central corneas in different groups.In 1 day, 3, 5, 7 days after modeling, the corneas were examined under the slit lamp microscope and scored, and corneal sections were prepared for the histopathological examination.Fungal activity was confirmed by plate counts, and real-time PCR was employed to assay the relative expressions of interleukin-1β (IL-1β) mRNA and tumor necrosis factor-α (TNF-α) mRNA in the corneas.


No morphological abnormality was seen in the corneas in the normal control group, CS-ETA/Ag/GO group and CS-ETA/Ag/GO/Vor group.Corneal inflammatory score was significantly lower in the CS-ETA/Ag/GO/Vor group in various time points, with a significant differences among the groups and time points (Fgroup=237.29, P=0.00; Ftime=260.33, P=0.00). The edema, necrosis or perforation of cornea were seen in the model control group, and slighter inflammatory response in the CS-ETA/Ag/GO group, and corneal edema was gradually disappear in the CS-ETA/Ag/GO/Vor group.The corneal fungal loads were highest in the model control group and lowest in the CS-ETA/Ag/GO/Vor group, with significant differences among the three groups and various time points (Fgroup=113.15, P=0.00; Ftime =126.52, P=0.00). The relative expressions of IL-1β mRNA and TNF-α mRNA in the corneas peaked in the fifth day after modeling in all of the three groups, and the expression levels of IL-1β mRNA and TNF-α mRNA in the corneas were lowest in the CS-ETA/Ag/GO/Vor group, showing significant differences among the groups and time points (IL-1β: Fgroup=189.90, P=0.00; Ftime=108.56, P=0.00; TNF-α: Fgroup=82.55, P=0.00; Ftime=44.36, P=0.00).


CS-ETA/Ag/GO/Vor delivery system plays an anti-fungal activity in fungal keratitis by the synergistic effect of voriconazole and Ag+ .In addition, CS-ETA/Ag/GO/Vor appears to have a good safety after topical application.

Key words:

Antifungal agents/therapeutic use; Voriconazole; Nanomedicine; Silver/pharmacology; Aspergillus fumigatus; Keratitis; Mice, inbred C57BL

Contributor Information

Zhong Jing
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China
Yuan Jin
Jiang Gangbiao
Chen Guopu
Sun Yifang
Chen Ling
Deng Yuqing
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Updated: March 31, 2023 — 9:07 am