Influence Of Electret 5-FU Patch In Wound Healing Of Rat Skin

Wounds are common problem in clinical surgery.Now the difficulty for wound treatment focuses on two aspects.The first is chronic wound resulting from complicated injury factors.They are difficult to improve and easy to recurrent.The second is excessive repairing or cell proliferation disorder,which may result in hypertrophic scar and the treatment is difficult and complicated.Current therapies for treatment of wounds focus on promotion of wound healing only,or treatment of hypertrophic scar due to the excessive repairing only.No single therapy has been adopted as the standard of care for clinical practice.Wound healing and scar formation are two successive stages in wound repairing phases.Therefore,promotion of wound healing and inhibition of scar proliferation should be considered as a whole project.In this paper,the electret was used as a supply source of electrostatic field and 5-fluorouracil(5-Fu)was used as a model drug to manufacture the electret 5-FU patch by using pharmacological technology.Some patch parameters,drug release behavior,transdermal drug delivery in vitro and in vivo were evaluated to study the effect of electret and 5-FU on regulation of wound repairing.The results were found in the following studies.1.Determination of some parameters of the patchThe influence of polarity,surface potential and action time of the electret in adhesive force and skin irritation of the electret patch were studied.The results suggested that all the electret,electret patch,electret 5-FU patch satisfied the requirement of experiment.The application of electret on 5-FU patch could,on one hand,change the structure of the patch matrix,decrease the viscosity of the patch;on the other hand,it could produce strong and stable electrostatic field on both sides of the patch,altering the distribution of drug in patch.The above two effects were proportional to the surface potential of the electret.2.5-FU release profile from electret 5-FU patchWe used improved Franz diffusion cell and high performance liquid chromatography(HPLC)to explore the regulation mechanism of electret on release profile of 5-FU from the patch.Result showed that the HPLC technology was of better specificity,high precision and accuracy in analysis of 5-FU.Electret could promote the natural release of drug from the patch by decreasing the viscosity of the matrix.Moreover,the distribution alteration of drug in patch caused by electret enhanced the effect of negative electret on drug release promotion,but offset the promotion effect of the positive electret.Therefore,electret might be used to regulate the drug release from the patch.The mathematic drug release profile is as follows:3.Studies on transdermal delivery of electret 5-FU patch in vitroThe in vitro transdermal delivery of 5-FU from electret 5-FU patch through normal and scar rat skin was performed.We found that electret 5-FU patch could significantly increase the transdermal delivery of the drug.The promotion effect was proportional to the surface potential of the electret.The higher was the surface potential of the electret,the more were the cumulative permeation amount and skin residual amount.Negative electret showed the better permeation enhancing effect than that of the positive electret that had the same absolute value of the surface potential.When electret with the same polarity and surface potential was applied to normal and scar skin respectively,normal skin had higher cumulative permeation amount,but lower in skin residual amount,as compared to those of scar skin.4.The in vivo animal studies of electret patch and electre 5-FU patchOn the basis of above studies,we performed the in vivo animal experiment to study the effect of electret and 5-FU on wound healing and scar growth.The results indicated that both the electret patch and electret 5-FU patch could produce strong and stable electrostatic field on both sides of the skin,changing the structure of stratum corneum and decreasing the barrier function of the skin,increasing the transdermal permeation of the drug.The promotion effect of electret on wound healing was proportional to the surface potential of the electret.But electret would not result in scar proliferation due to the excessive wound repairing.5-FU transdermal formulation could inhibit the excessive proliferation of scar at the late stage of wound healing.The combination of electret and5-FU could effectively inhibit the scar growth.In conclusion,electret 5-FU transdermal delivery system could accelerate the wound healing and inhibit the scar growth by regulating the parameter of the electret and drug content loaded in the system,as well as scientific designing of drug administration,therefore to provide positive and useful reference in wound treatment.