A Study Of Combining Nano-microneedle With 5% Minoxidil In Androgenetic Alopecia Treatment

Objective:Androgenetic alopecia(AGA)is the most prevalent type of hair loss at present.The etiology and nosogenesis of the disease,which related to many signal pathways as well as were influenced by various elements,are complicated and there are no ideal treatments for curing it so far.Minoxidil is one of the drugs which US Food and Drug Administration(FDA)approves to treat AGA.It is effective and widely accepted without much side effect.However,the amount of transdermal absorption is limited and it takes a long time to take effect of hair growth.So we can use physical technique to enhance the transdermal drug delivery in order to improve the efficacy of topical drug.Nano-microneedle is used to facilitate penetration with producing a great amount of micro channel across the stratum corneum.In this study,we aimed to evaluate the efficacy and safety of combining nano-microneedle with 5% minoxidil in androgenetic alopecia treatment,and made a comparison to only use 5% minoxidil externally.Furthermore,the pathogenesis of AGA and the mechanism of action of minoxidil on hair growth were investigated.Methods:36 Chinese patients were recruited in the clinical trial and another 6 volunteers with the same disease were taken scalp tissue sampling which used in the laboratory investigation.Subjects were 22 to 50 years old and diagnosed to be the androgenetic alopecia according to clinical manifestation.Informed consent was obtained from each patient.In a randomized,single-blind method,the first 36 patients were divided into three groups which includes using nano-microneedle to deliver normal saline(NS),5%minoxidil and delivering 5% minoxidil by nano-microneedle.Digital photography was taken,secretion of grease,density and diameter of hair were measured before treatment and every month.The subjects evaluated the therapy by score and reported the pain grade.Moreover,there was a period of three months for return visit.For another 6 patients,they were divided into 5% minoxidil group and delivering 5% minoxidil by nano-microneedle group.The scalp tissue samples were taken from bald area before and after treatment,as well as the relatively normal area before treatment.Applying Hematoxylin and eosin(HE)stain to find out if differences of the amount and morphology of hair follicle existed between different scalp area,or appeared after treatment.Quantitative real-time quantitative polymerase chain reaction(q RT-PCR)was taken to test the expression of vascular endothelial growth factor(VEGF)and bone morphogenetic protein receptor?A(BMPR-?A).Results:All of the patients completed the treatment.According to the clinical trial,we found out that statistically significant difference did not show in any index after the treatment for the NS group(p>0.05).For the groups of 5% minoxidil and delivering 5%minoxidil by nano-microneedle,the density and diameter of hair increased(p<0.05),the secretion of grease decreased(p<0.05).And the result of the hair density in the latter group show a more signicant difference(p<0.05).Nearly 42 percent of the scores given by subjects to evaluate the pain of nano-microneedle were 1,which meant the pain brought from the nano-microneedle was very slight.After the four-month treatment,the mean scores for the efficacy,which were collected from groups of 5% minoxidil and delivering 5% minoxidil by nano-microneedle,were 2.69(slight to moderate improvement)and 3.06(at least had moderate improvement).For the results of laboratory experiments,there were more hair follicles in normal scalp area than bald area according to HE stain.And after the treatment of using 5% minoxidil or delivering 5% minoxidil by nano-microneedle,the number of hair follicles increased.The experiment of q RT-PCR showed downregulation in VEGF and BMPR-?A in bald area,which were 0.46 and0.44 times the expression in normal scalp area.Four-month treatment later,the expression of VEGF didn't have a signicant difference compared with the situation before the treatment in the group using 5% minoxidil(p>0.05),while it upregulated in the group delivering 5% minoxidil by nano-microneedle(p<0.05).As for the expression of BMPR-?A,the difference between before and after treatment were not statistically significant(p>0.05)both in two groups.Conclusion:5% minoxidil is an effective topical drug for Androgenetic alopecia.Delivering 5% minoxidil by nano-microneedle which enhances the cutaneous permeation of drug is safe,and show a better efficacy in treating AGA compared with merely using5% minoxidil externally.The expression of VEGF and BMPR-?A downregulates in bald area of AGA patients,thus there may be some connection between AGA and VEGF signal pathway as well as BMP signal pathway.