Effect Of Nanoscale 5-FU Ethosomes On Hyperplastic Scars Of Rat Sciatic Nerve

Objective: To evaluate the effect of nanoscale 5-Fluorouracil Ethosomal Suspension(5-FU ES)on hyperplastic scars on nerves' anastomoses.Sciatic nerve injury in vitro and in vivo(rats)were used as model.Methods: Nanoscale 5-FU ES was prepared and characterized by transmission electron microscope and particle size analyzer.In vitro,optimal nanoscale 5-FU ES concentrations and culture times were established in mixed culture systems of primary nerve fibroblasts and dorsal root neurons.Western blotting and real-time PCR were used to determine the effect of nanoscale 5-FU ES on type I collagen secretion and mRNA expression level in hypertrophic scar fibroblasts.Sciatic nerve injuries were induced in rat models in order to observe neuromyelin morphology of the anastomosis(H-E staining),numbers of myelin content during the nerve fiber regeneration and G values(Tuloidine Blue(TB)staining)in different treatment groups.Results :(1)Compared with the control group,statistic significance of the inhibitory effect in the mixed culture systems of primary nerve fibroblasts and dorsal root neurons was found for the 0.03%(w/v)nanoscale 5-FU ES group at 48 hours(P<0.05).(2)Western blot and Realtime PCR results showed that the inhibitory effect on nerve scar fibroblasts was most prominent in the mixed culture with 0.03%(w/v)nanoscale 5-FU ES after 48 hours(P<0.05).(3)H-E staining showed a less number and more regular collagen fibers arrangement in nerve anastomosis in the nanoscale 5-FU ES treated group as compared to the NS and Transaction group.(4)Regenerated nerve fibers were observed in the negative control,positive control and nanoscale 5-FU ES group by Tuloidine blue staining.There were less and finer medullary nerve fibers,as well as a slight edema in the local interstitium in the NS and Transaction groups.The opposite was found in nanoscale 5-FU ES group.(5)The G value for myelin thickness was statistically significant in the nanoscale 5-FU ES group as compared with the control group(P < 0.01).Conclusion: The nanoscale 5-FU ES can exert a sustained inhibitory effect on the formation of scar tissue,while promoting nerve regeneration and effectively recovering nerve function in the anastomosis area after peripheral nerve injury.The underlying mechanism is based on the inhibition of type I collagen expression in fibroblasts.