Experimental Study Of The Ethosomes Encapsulated With 5-Fluorouracil In The Treatment Of Hypertrophic Scar Mediated By CO₂ Fractional Laser

Objective:This study was designed to observe the effect of CO₂ fractional laser on the promotion of the ethosomal gel encapsulated with 5-FU in hypertrophic scar tissue as well as the duration of the effect.And evaluate the therapeutic effect of CO₂ fractional laser combined with 5-FU EG on rabbit ear hypertrophic scar.Methods:1.5-FU ES was prepared by Touitou method,and then was prepared into 5-FU EG.Characterization of 5-FU EG were determined by particle sizer system,and their entrapment efficiency was detected by ultracentrifugation and microcolumn centrifugation.Morphology of 5-FU EG was evaluated by transmission electron microscope.2.CO₂ fractional laser on the promotion of the ethosomal gel encapsulated with 5-FU was ealuated in hypertrophic scar in vitro.The permeated amount of5-FU and retention contents of 5-FU were both calculated by HPLC.Fluorescence intensities of 5-FU ES labeled with Rodanmin 6GO were measured by CLSM.3.The promotion of 5-FU ES labeled with Rodanmin 6GO in rabbit ear hypertrophic scar by CO₂ fractional laser was evaluated at 0h,6h,12h,24h,3days and 7 days after the irradiation.The opening rate of the micro channel channel was calculated according to CLSM.4.The therapeutic effect of CO₂ fractional laser combined with 5-FU EG was evaluated on rabbit ear hypertrophic scar.Relative thickness of rabbit ear hypertrophic scar was measured by caliper with meter measuring before and after the treatment.SEI(scar index)of rabbit ear hypertrophic scar was measured in HE staining.Results:1.Prepared ethosomes was nanoscale(<100nm).By comparing the particle size,PDI and entrapment efficiency,5-FU ES and 5-FU EG were found to have a P>0.05 which indicates that the particle size,PDI and entrapment efficiency of the prepared 5-FU ES and 5-FU EG have no significant difference,P>0.05.2.Within 1 hour,the penetration amount of 5-FU(?g/m L/cm²)of experimental group(5-FU EG combined with the affect of CO₂ fractional laser)was 4.15±2.22,which was higer than that of control group(5-FU EG):0.73±0.33(P<0.05).Within 24 hours,the penetration amount of 5-FU of experimental group was 107.61±13.27,which was higer than that of control group:20.73±3.77(P<0.05).And the retention contents of 5-FU(?g/cm²)of experimental group was 24.42±4.37,which was higer than that of control group:12.25±1.64(P<0.05).The fluorescence intensity of Rho in hypertrophic scar tissues of experimental group was 59.61±6.39,which was higer than that of control group:6.39±1.64(P<0.05)after 1 hour.The fluorescence intensity of Rho in hypertrophic scar tissues of experimental group was 163.32±13.23,which was higer than that of control group:49.89±4.01(P<0.05)after 6 hours.The fluorescence intensity of Rho in hypertrophic scar tissues of experimental group was 270.36±16.89,which was higer than that of control group:148.25±8.73(P<0.05)after 24 hours.3.The opening rate of the micro channel channel was 100%0 hour and 6hours after the irradiation by CO₂ fractional laser.When it comes to 12 hours after the irradiation by CO₂ fractional laser,the opening rate of the micro channel channel was 90.59%,and dropped to 15.58%24 hours after the irradiation.The opening rate of the micro channel channel was 0%3 days and 7days after the irradiation by CO₂ fractional laser.4.The relative thickness of rabbit ear hypertrophic scar after 7 days'treatment was:experimental group(5-FU EG combined with the affect of CO₂fractional laser,1.27±0.15)<control group A(CO₂ fractional laser,1.35±0.09)<control group B(5-FU EG,1.52±0.10)<control group C(control,1.61±0.15).The SEI of rabbit ear hypertrophic scar after 7 days'treatment was:experimental group(1.16±0.08)<control group A(1.22±0.10)<control group B(1.32±0.13)<control group C(1.49±0.08).Conclusions:1.There was no significant difference in characterization of the particle size,PDI and entrapment efficiency between 5-FU EG and5-FU ES.2.CO₂ fractional laser can rapidly and significantly promote the permeability of 5-FU EG in hypertrophic scar tissues.3.The effective promotion of CO₂ fractional laser to the permeability of5-FU EG in rabbit ear hypertrophic scar began to disappear 24 hours after the irradiation,so the critical period for promotion of CO₂ fractional laser to the permeability of 5-FU EG is within 24 hours.4.CO₂ fractional laser combined with external use of 5-FU EG can be effective in the treatment of hypertrophic scar.CO₂ fractional laser itself,penetration promotion by CO₂ fractional laser and 5-FU EG play the important roles in the treatment of the rabbit ear hypertrophic scars.