Microneedle Array Drug Delivery Technologies For The Treatment Of Hypertrophic Scars

Objective Observe the therapeutic effect of hypertrophic scars of the microneedle arraytransdermal penetration of triamcinolone acetonide through different methods ofadministration, and explore new ways for the treatment of hypertrophic scars. MethodsEstablish nude mouse models of human hypertrophic scars: human HS tissue weretransplanted in24nude mice surface, then observe the tissue structure and survival conditionof the scars after transplantation. Elution method, homogenization were investigatedadministered1h,12h scar skin triamcinolone acetonide in vivo absorption characteristics;transepidermal water loss (TEWL) measurements, laser Doppler blood flow method examineits skin irritation. In vitro scars: Human isolated hypertrophic scars dealt with microneedlearrays, dyed by methylene blue, in order to observe the distribution and arrangement of themicropores and the depth, width and density of the micropores by paraffin section after HEstaining. Body scars: Set up nude mice hypertrophic scar models which were transplantedfrom human hypertrophic scars, use triamcinolone acetonide acetate emulsifiable paste to dopharmacodynamics experiments, divided them into microneedle group, the blank group, andthe coating group, using direct coating administration and microneedle transdermal drugdelivery, to observe the expression of the α-SMA, the density of the blood vessels in the scarsby CD34through the immunohistochemistry and the changes of the apoptosis by TUNELmethods in the15d,30d,45d and60d, and finally used image analysis system for statisticalanalysis. Results24nude mice transplanted people HS and22nude mice among themappeared apparent HS(91.66%), which were significantly higher than the surrounding normaltissue, their surface were roughness, congestion significantly, hard texture, disordered arrangement of collagen bundles in the tissue, collagen fibers density and we could see a largenumber of microvascular. After the treatment of the microneedle arrays of the length of250μm,500μm and1000μm in the vitro scars, we could see the micropores arrangeduniformly, and the depth had already penetrated the stratum corneum to reach the epidermisprickle cell layer, the average depth, width and the number of the micropores were89±32μm,48±9μm and76±2μm in the group of the500μm microneedle array group, which was moresuitable for the body scar administration than the other two groups. After the treatment ofMicroneedles1and12h,27.42%and60.64%drugs were respectively absorbed into the skin,and the penetration enhancers actions were3.43and2.51times. The drug retention was stillthe highest after12h through the intradermal injection, while it was still decrease45.98%compared with administered1h. The microneeedles and cream directly respectively increased5.46and4.18times compared with administered1h; the microneedles’s promoting effect tothe drug retention of the skin was3.56times. Intradermal injection12h of drug retention inthe skin was not evenly distributed, with mean (4.83±5.51) μg, microneedles for12h meanonly (0.93±0.14) μg, but the distribution was relatively uniform. TEWL measurementsdisplayed that microneedle delivery and had no significant differences in the intradermal skinirritation, but the method of laser Doppler blood flow displayed that the intradermal skinirritation was8.40times compared with microneedle administration. Measured the density ofthe blood vessels in the scars by CD34after the pharmacodynamics of the nude scar models,the microneedle group and the injection group was lower than the coating group in the30d,45d and60d, the differences between them were statistically significant(P＜0.05). Theinjection group`s α-SMA positive cells optical density in the scars was significantly less thanthe coating group`s, and the difference between them was statistically significant(P＜0.05),while the positive expression of the microneedle group was significantly less than the coatinggroup at the period of15d later(p＜0.05), and decreased to the level of the injection group atthe period of30d and45d later. The number of the apoptotic cells in the microneedle group showing a trend of increase with the extension of the treatment time, and the injection group’swas significantly higher than the coating group`s in each time(P＜0.005), the microneedlegroup`s apoptotic cell was higher than the coating group`s in the30d,45d and60d(P＜0.05).Conclusions The penetration efficiency of the triamcinolone which were used in the skin ofthe nude mice scars by the effectively promote transparent of the microneedle arrays, whichcan inhibit the growth of the hypertrophic scars.