期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 58, 期 11, 页码 4499-4505出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.17-22301
关键词
hydrogel; drug delivery; antimicrobial; amphotericin; bandage lens; cornea; keratitis
资金
- Wolfson Foundation
- Institute of Ageing and Chronic Disease, University of Liverpool
- Engineering and Physical Sciences Research Council (EPSRC) [EP/M002209/1]
- Spheritech Ltd.
- EPSRC [EP/M002209/1] Funding Source: UKRI
- MRC [MR/R006334/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/M002209/1] Funding Source: researchfish
- Medical Research Council [MR/R006334/1] Funding Source: researchfish
PURPOSE. The purpose of this study was to develop a more efficient drug delivery device to overcome the limitations of current drop therapy for the treatment of fungal keratitis. METHODS. Amphotericin B (AmpB), 0 to 30 mu g/mL, was associated with a poly-epsilon-lysine (peK) hydrogel. Fungicidal effect against Candida albicans was assessed at 18 and 42 hours by optical density (OD600) and growth on agar. Tear film dilution effect was mimicked by storage of AmpB peK gels in 3.4 mL sterile PBS for 24 hours prior to fungal incubation. Drug elution over 96 hours was evaluated by HPLC, and drug stability was tested while associated with the gel by OD600 up to 48 hours. Lack of cytotoxicity toward the HCE-T corneal epithelial cell line was assessed over 7 days. RESULTS. AmpB peK gels show fungicidal activity in normal conditions (0.057 OD600, SD 0.003, P < 0.005) and in the presence of horse serum (0.048 OD600, SD 0.028 P < 0.005) at 18 hours. The drug release profile was above therapeutic levels (0.188 mu g/mL) for up to 72 hours. Tear dilution had no significant effect at higher concentrations of AmpB (3 to 10 mu g/ mL). AmpB peK gels were not cytotoxic to the HCE-T cell line. CONCLUSIONS. We demonstrated that AmpB peK gels confer sustained therapeutic antifungal activity for at least 48 hours without corneal epithelial cell line cytotoxicity, suggesting their potential for in vivo use as an antifungal bandage contact lens. This could avoid the need for intensive topical medication in the treatment of fungal keratitis.
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