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Published on: September 12, 2014
Development of a Poly-ε-Lysine Contact Lens as a Drug Delivery Device for the Treatment of Fungal Keratitis
Andrew G Gallagher1,2, Keri McLean1,3, Rosalind M K Stewart1,3
1Department of Eye and Vision Science, Institute of Ageing and Chronic Diseases, University of Liverpool, Liverpool, United Kingdom.
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 microg/mL, was associated with a poly-ε-lysine (pεK) 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 pεK 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 pεK 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 microg/mL) for up to 72 hours. Tear dilution had no significant effect at higher concentrations of AmpB (3 to 10 microg/mL). AmpB pεK gels were not cytotoxic to the HCE-T cell line.
Conclusions:
We demonstrated that AmpB pεK 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.
Insights
This study developed a new hydrogel drug delivery system for Amphotericin B to treat fungal keratitis. The new system provides sustained antifungal activity and is safe for corneal cells.
Area of Science:
- Ophthalmology
- Biomaterials Science
- Mycology
Background:
- Fungal keratitis is a serious eye infection often treated with topical drops.
- Current drop therapy faces limitations including poor retention and frequent administration.
- A need exists for improved drug delivery devices for sustained ocular antifungal treatment.
Purpose of the Study:
- To develop an efficient drug delivery device for treating fungal keratitis.
- To create a poly-ε-lysine (pεK) hydrogel loaded with Amphotericin B (AmpB).
- To evaluate the efficacy and safety of the AmpB-loaded pεK hydrogel for ocular application.
Main Methods:
- Amphotericin B (AmpB) was incorporated into poly-ε-lysine (pεK) hydrogels.
- Fungicidal activity against Candida albicans was assessed.
- Drug elution kinetics and stability within the hydrogel were evaluated.
- Cytotoxicity was tested on the HCE-T corneal epithelial cell line.
Main Results:
- AmpB pεK gels demonstrated significant fungicidal activity.
- Sustained drug release above therapeutic levels was observed for up to 72 hours.
- The hydrogel showed no significant cytotoxicity to corneal epithelial cells.
- Tear dilution had minimal impact on drug efficacy at higher concentrations.
Conclusions:
- AmpB pεK hydrogels provide sustained antifungal activity for at least 48 hours.
- The developed hydrogel is non-cytotoxic to corneal epithelial cells.
- This technology holds potential for use in antifungal bandage contact lenses for fungal keratitis treatment.
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