A semi-solid drug delivery system for epidermal growth factor in corneal epithelial wound healing

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Abstract
Purpose. To examine the effects of EGF, delivered from a semi-solid drug delivery system, on corneal epithelial wound healing following anterior keratectomy wound creation in the eyes of New Zealand white rabbits. Methods. A semi-solid drug delivery system based on a Carbopol gel was developed. Following creation of a 7.5 mm circular anterior keratectomy wound, 50 µL of either a placebo gel or an EGF-containing gel, was instilled in the inferior fornix. The gel remained in the eye for 8 hours, at which time it was removed. Anaesthesia was maintained for the entire 8-hour period. Wound healing was evaluated by quantitative morphometry. We evaluated 0.04, 0.1, 0.2, 0.4, and 1% EGF concentrations in the gel. Tear EGF concentrations and histology of the healing corneas were also examined. Results. The enhancement factor (ratio of the healing rate with the EGF gel and control gel) was 1.13 ± 0.12, 1.40 ± 0.14, 1.29 ± 0.12, 1.80 ± 0.22, and 1.09 ± 0.12 for the gels containing 0.04, 0.1, 0.2, 0.4, and 1% EGF by mass, respectively. The increases in the rate of wound healing were significant with the 0.1, 0.2 and 0.4% gel formulations. Histologically, the 0.4% gels resulted in cellular hyperplasia after 5 days of healing. Differences between the placebo gel-treated and EGF-containing gel-treated eyes were evaluated at both 2 and 5 days. The concentration of EGF in the tears during the treatment period was approximately constant for both the 1% and 0.04% gels. The average tear concentration during the instillation period was 2.87 ± 0.36 µg/mL and 200.61 ng/mL ± 116.10 for the 1% and 0.04% gels respectively. Conclusions. Treatment with EGF in a Carbopol gel carrier for a period of 8 hours results in significant wound healing enhancement (p < 0.05). The optimum EGF loading in the gel was determined to be 0.4%. A slow release gel may be an effective way to deliver EGF to the corneal surface.