Development of a Poly-ε-Lysine Contact Lens as a Drug Delivery Device for the Treatment of Fungal Keratitis

被引:28
|
作者
Gallagher, Andrew G. [1 ,2 ]
McLean, Keri [1 ,3 ]
Stewart, Rosalind M. K. [1 ,3 ]
Wellings, Don A. [2 ]
Allison, Heather E. [4 ]
Williams, Rachel L. [1 ]
机构
[1] Univ Liverpool, Inst Ageing & Chron Dis, Dept Eye & Vis Sci, Apex Bldg,West Derby St, Liverpool L7 8TX, Merseyside, England
[2] SpheriTech Ltd, Runcorn, Cheshire, England
[3] Royal Liverpool Univ Hosp, St Pauls Eye Unit, Liverpool, Merseyside, England
[4] Univ Liverpool, Inst Integrat Biol, Dept Funct & Comparat Genom, Liverpool, Merseyside, England
基金
英国工程与自然科学研究理事会;
关键词
hydrogel; drug delivery; antimicrobial; amphotericin; bandage lens; cornea; keratitis; CANDIDA-ALBICANS; PENETRATION;
D O I
10.1167/iovs.17-22301
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
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.
引用
收藏
页码:4499 / 4505
页数:7
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