Abstract
ObjectiveThis study is designed to explore permeability of ethosomes encapsulated with 5-florouracil (5-FU) mediated by CO2 fractional laser on hypertrophic scar tissues. Moreover, therapeutic and duration effect of CO2 fractional laser combined with 5-FU encapsulated ethosomes in rabbit ear hypertrophic scar model will be evaluated.MethodsThe 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 CO2 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.ResultsThe 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 CO2 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.ConclusionCO2 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.
Highlights
Hypertrophic scar is a cutaneous condition characterized by deposits of excessive amounts of collagen which gives rise to a raised scar, but not to reach the observed degree of keloids [1]
Quality Assessment of Ethosomes Encapsulated with 5-florouracil(5E) First of all, to validate the quality of ethosomal gel encapsulated with 5-florouracil (5E), the morphology and diameters were detected by transmission electron microscope (TEM) observation
Using laser particle size analyzer, ethosomes in suspension state appear to be with a diameter of 87.72 ± 9.27 nm, and the polydispersity index (PDI) was 0.10 ± 0.01
Summary
Hypertrophic scar is a cutaneous condition characterized by deposits of excessive amounts of collagen which gives rise to a raised scar, but not to reach the observed degree of keloids [1]. About 60% of patients developed hypertrophic scars postoperatively, typically during the first 3 months. Radiation therapy, chemotherapy, and other medication surgical treatments are the major therapy treatment. These therapies could not achieve the desired therapeutic effect due to their defects [4, 5]. Drug therapy is one of the most common non-surgical treatments for pathological scar to external painting based on local injections. Due to drug side effects, local injections are often limited to small-scale and low-dose treatment. Despite of the advantages including painless, no side effect to the liver, and convenient for long-term external usage [7, 8], drugs could not enter the scar due to special organizational structure of pathological scars.
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