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Objective  This study is designed to explore permeability of ethosomes encapsulated with 5-florouracil (5-FU) mediated by CO 2  fractional laser on hypertrophic scar tissues. Moreover, therapeutic and duration effect of CO 2  fractional laser combined with 5-FU encapsulated ethosomes in rabbit ear hypertrophic scar model will be evaluated.    Methods  The permeated amount of 5-FU and retention contents of 5-FU were both determined by high-performance liquid chromatography (HPLC). Fluorescence intensities of ethosomes encapsulated with 5-FU (5E) labeled with Rodanmin 6GO (Rho) were measured by confocal laser scanning microscopy (CLSM). The permeability promotion of 5E labeled with Rho in rabbit ear hypertrophic scar mediated by CO 2  fractional laser was evaluated at 0 h, 6 h, 12 h, 24 h, 3 days and 7 days after the irradiation. The opening rates of the micro-channels were calculated according to CLSM. The therapeutic effect of 5EL was evaluated on rabbit ear hypertrophic scar in vivo. Relative thickness of rabbit ear hypertrophic scar before and after the treatment was measured by caliper method. Scar elevation index (SEI) of rabbit ear hypertrophic scar was measured using H&E staining.    Results  The data showed that the penetration amount of 5EL group was higher than 5E group (4.15 ± 2.22 vs. 0.73 ± 0.33;  p  < 0.05) after 1-h treatment. Additionally, the penetration amount of 5EL was higher than that of the 5E group (107.61 ± 13.27 vs. 20.73 ± 3.77;  p  < 0.05) after 24-h treatment. The retention contents of the 5EL group also showed higher level than 5E group (24.42 ± 4.37 vs.12.25 ± 1.64;  p  < 0.05). The fluorescence intensity of Rho in hypertrophic scar tissues of the 5EL group was higher than that of the 5E group at different time points (1, 6, and 24 h). The opening rates of the micro-channels were decreased gradually within 24 h, and micro-channels were closed completely 3 days after the irradiation by CO 2  fractional laser. The relative thickness and SEI of rabbit ear hypertrophic scar after 7 days of treatment in the 5EL group were significantly lower than the 5E group.    Conclusion  CO 2  fractional laser combined with topical 5E can be effective in the treatment of hypertrophic scar in vivo and supply a novel therapy method for human hypertrophic scar.

Experimental Study of 5-fluorouracil Encapsulated Ethosomes Combined with CO2 Fractional Laser to Treat Hypertrophic Scar