金属和可溶性微针及其使用参数对皮肤孔道形成与闭合的影响

Effects of metal or dissolving microneedles and its parameters of operation on the formation and closure of skin microchannels

本文主要研究金属和可溶性微针对皮肤微孔道形成与闭合的影响因素及效果。采用不同长度、针尖间距和基座面积的金属(不锈钢)微针,形状分别为铅笔形和圆锥形,以及不同针尖间距的铅笔形可溶性微针。将微针刺入在除毛小鼠和大鼠的皮肤上,通过经皮水分丢失(transepidermal water loss,TEWL)法和亚甲蓝染色法研究微针施用参数、自身参数和动物对孔道产生的影响;通过视觉观察微针引起的皮肤局部刺激性现象。动物实验已获得浙江工业大学实验动物福利与伦理委员会批准。不锈钢金属微针刺入皮肤后保持30 s以上,刺入力分别为2、4和8 N,形成孔道的TEWL初始值分别为12.9、33.0和40.4 g·m^(-2)·h^(-1);当长度分别为400、600和800μm,形成孔道的TEWL初始值分别为37.1、40.4和49.5 g·m^(-2)·h^(-1);当针尖间距分别为400、600和800μm,形成孔道的TEWL初始值分别为33.2、40.4和55.8 g·m^(-2)·h^(-1);当基座面积分别为0.16、0.35和0.62 cm2,形成孔道的TEWL初始值分别为35.1、40.4和67.1 g·m^(-2)·h^(-1),而圆锥形和铅笔形的微针产生的影响是近似的。铅笔形的可溶微针刺入皮肤,针尖间距分别为400、600和800μm,形成孔道的TEWL初始值分别为49.8、60.5和70.5 g·m^(-2)·h^(-1)。不同性别和品系动物皮肤的TEWL基线值有所不同,但是孔道形成与闭合的趋势近似。微针引起的轻微红斑在24 h内消退。不同参数微针对皮肤孔道产生的影响有一定差异,但孔道都可在24或48 h内闭合,皮肤局部刺激性轻微。

To investigate the influence factors and effects of metal or dissolving microneedles on the formation and healing of skin microchannels,the pencil-shaped or conical stainless steel microneedles with different lengths,tip to tip space and base area,and the pencil-shaped dissolving microneedles with different tip to tip space were used.The microneedles were applied to the skin of epilatory mice and rats,and the effects of various microneedle parameters,application parameters,and animals on the microchannels were explored by the transepidermal water loss(TEWL)and methylene blue staining.Visually observe the skin local irritation caused by the microneedles.The animal experiments were approved by the Animal Experiments Welfare and Ethical Committee of Zhejiang University of Technology.The application time of the microneedle should be maintained at 30 s or more.When the insertion forces were 2,4,8 N,and the TEWL initial values of the formed microchannels were 12.9,33.0,40.4 g·m^(-2)·h^(-1),respectively.When the length of metal microneedle were 400,600,800μm,and the TEWL initial values of the formed microchannels were 37.1,40.4,49.5 g·m^(-2)·h^(-1),respectively.When the tip to tip space of metal microneedle were 400,600,800μm,and the TEWL initial values of the formed microchannels were 33.2,40.4,55.8 g·m^(-2)·h^(-1),respectively.When the base area of metal microneedle were 0.16,0.35,0.62 cm2,and the TEWL initial values of the formed microchannels were 35.1,40.4,67.1 g·m^(-2)·h^(-1),respectively.The effects of conical and pencil-shaped microneedles are similar.When the tip to tip space of pencil shaped dissolving microneedle were 400,600,800μm,and the TEWL initial values of the formed microchannels were 49.8,60.5,70.5 g·m^(-2)·h^(-1),respectively.The TEWL baseline values of animal skins of different genders and series are different,but the tendency of microchannels formation and closure is similar.Visual inspection revealed that the slight erythema caused by the microneedles subsided within 24 h.Microneedles of different parameters have different effects on microchannels.The microchannels closed within 24 or 48 h,and the skin local irritation caused by microneedle was mild.