The Effect Of A Combination Of Electret And Chemical Enhancer On In Vitro Transdermal Behavior Of 5-fluorouracil Through Scar And Normal Skin

Overgrowing scar or keloid is an over growth of collegan in the process of scar healing due to the uncontrollable rate of collegan biosynthesis and metabolism.Scar not only affects both the appearance of the patient and the normal function of the skin tissues,it may also lead to disability if it is much serious,resulting in physiological and psychological problems.Nowadays,treatment of scar can be extremely difficult,as there is no such an approach with low toxicity,high proficiency,and better patient compliance.In recently years,5-fluorouracil(5-FU)has been studied and proved to be an effective option for scar treatment.5-FU has a molecular weight of 130.08 Da and is soluble in basic solution.A 5-FU transdermal delivery system has the advantages of controlled and sustained drug release,biosafety,and high patient compliance.When5-FU transdermal delivery system is used together with electret,its properties of controlled and sustained drug release can be further improved.In this paper,we used5-FU as model drug,electrets with different surface potentials and polarities as physical enhancer,azone,ethyl oleate and propylene glycol etc.as chemical enhancers,scar skin,normal basal and abdominal skin from SD rats as skin samples,to study the transdermal behaviors of 5-FU through scar and normal skin under the action of either electret or chemical enhancer alone,or both the electret and chemical enhancer.We hope our study could be of some significance for scar treatment in clinic.Our study is divided into four parts as follows.1.Effect of electrets on in vitro transdermal behaviors of 5-FU solutionThe corona discharge method was employed to prepare positive/negative polypropylene(PP)electrets with different surface potentials.The in vitro transdermal behaviors of 5-FU through scar skin and normal skin(basal skin and abdominal skin)of SD rat,as well as the retention amount of 5-FU in stratum cornemu(SC)and SC stripped skin were studied using improved Franz diffusion cells.The results showed that(1)The in vitro transdermal behavior of 5-FU through the normal and scar rat skin were almost the same under the action of electrets.The abdominal skin had the maximum drug permeation amount,while the scar skin the least.(2)As compared to the control group(untreated by electrets),the positive electrets suppressed the percutaneous permeation of 5-FU,but the negative electrets had theopposite effect.The higher surface potential of the negative electrets had more cumulated permeation amount of 5-FU.(3)After being treated by the electrets with the same polarity and magnitude of surface potential,the scar skin had more retention amount of5-FU in SC and SC stripped skin than that of in control group,as well as than that of in normal skin.(4)In comparison with the effect of negative electrets,positive electrets could result in more retention amount of 5-FU in scar skin,which was better for treatment of growing scar.2.In vitro transdermal behavior of 5-FU under the action of chemical enhancersIn this paper,1% azone,3% azone,5% azone,10% ethyl oleate and 7.5% propylene glycol were used to study the effect of chemical enhancers on in vitro permeation of5-FU through normal and scar rat skin and the distribution of the drug in skin.The results showed that(1)All the investigated chemical enhancers provided enhancement in 5-FU skin permeation as compared to control group(in absence of chemical enhancer).The top ranked effective enhancer was 3% azone.(2)3% azone group showed the most retention amount of 5-FU in SC and deep layer of basal,abdominal and scar skins as compared to control group and other chemical enhancer groups.The drug amount in skin also increased more after 10% ethyl oleate was employed.(3)Both the 3% azone and 10% ethyl oleate were selected to perform the following experiment.3.The combination effect of electrets and chemical enhancer on in vitro transdermal behavior of 5-FUThe electret with different polarity and surface potential was used in combination with 3% azone or 10% ethyl oleate respectively to study the in vitro permeation behavior of 5-FU through normal and scar skin and the distribution of drug in skin.The results might help us to optimize the scheme for combination usage of electrets and chemical enhancer.The results indicated that(1)Electrets with surface potential of 5000 V or higher than 5000 V decreased the percutaneous permeation amount of 5-FU when they were used together with 3% azone.(2)In comparison with the effect of single application of3% azone or electret,negative electret combined with 3% azone significantly increased the percutaneous permeation amount of 5-FU.(3)The combination of 5000 V electret and3% azone obviously increased the retention amount of 5-FU in SC and deep layer of normal and scar skin,as compared to single use of 3% azone or electret.The retention amount of 5-FU in SC stripped skin of scar was more than that of in SC,and far more than that of the percutaneous permeation amount,which was expected not only to provide more drug for scar treatment,but also to reduce the potentials for toxicity and side effects of drugs in vivo.The effect of combination of electret and 10% ethyl oleate on percutaneous permeation amount and skin retention amount of 5-FU was lower than combination of electret and 3% azone.4.The in vitro transdermal behavior of electre 5-FU patchIn this part,the 5-FU adhesive patch and 5000V/-5000 V electret 5-FU patches were prepared to study the effects of electrets on in vitro release and transdermal behavior of the drug from the patch.The result was expected to provide guidance for further studies of treatment of scar using electret 5-FU patch in vivo.The results indicated that the in vitro release amount and percutaneous permeation amount of 5-FU from the electret drug patches were higher than those of from the 5-FU adhesive patch.The application of electret 5-FU patch also reduced the retention amount of 5-FU in SC and SC stripped skin as compared to the application of 5-FU adhesive patch.The reasons for the results might be the effect of external electrostatic field of electrets on dielectric property of the matrix and the viscosity of the patch.Therefore,we will consider to apply the electrets in combination with chemical enhancer and to regulate the electric parameter of the electrets to increase the release amount of 5-FU from the electrets drug patch and the retention amount of drug in skin.