Enhanced skin delivery of vismodegib by microneedle treatment
Enhanced skin delivery of vismodegib by microneedle treatment
复制标题
DOI：
10.1007/s13346-015-0241-3
复制
发表时间：
2015-08-01
影响因子：
5.4
通讯作者：
Banga, Ajay K.
中科院分区：
文献类型：
--
作者：
Nguyen, Hiep X.;Banga, Ajay K.
本研究研究了微针处理(麦芽糖微针、Admin Pen （TM) 1200和Admin Pen (TM) 1500）在不同针长、皮肤平衡时间和微针插入时间下对vismodegib体外透皮给药的影响。还评估了微针处理对微通道尺寸（染料结合、钙黄蛋白成像、组织学和共聚焦显微镜研究）、经皮失水和vismodegib皮肤渗透性的影响。使用流变仪评估皮肤粘弹性，并用扫描电子显微镜表征微针的几何形状。采用垂直Franz扩散池研究了vismodegib在猪耳皮肤中的渗透作用。用体外重建的人表皮模型评估了维莫地吉制剂的皮肤刺激电位。体外渗透研究结果显示，维莫替吉通过微针处理皮肤的渗透显著增强。当针长从500增加到1100和1400 μ m时，给药量分别从14.50 +/- 2.35增加到32.38 +/- 3.33和74.40 +/- 15.86 μ g/cm(2)。药物通透性与微针治疗时间呈正相关。平衡时间也会影响vismodegib的递送。因此，微针长度、平衡时间和治疗持续时间的变化改变了vismodegib的透皮给药。
The present study investigated the effects of microneedle treatment (maltose microneedles, Admin Pen (TM) 1200, and Admin Pen (TM) 1500) on in vitro transdermal delivery of vismodegib with different needle lengths, skin equilibration times, and microneedle insertion durations. The influence of microneedle treatment on the dimensions of microchannels (dye binding, calcein imaging, histology, and confocal microscopy studies), transepidermal water loss, and skin permeability of vismodegib was also evaluated. Skin viscoelasticity was assessed using a rheometer, and microneedle geometry was characterized by scanning electron microscopy. Permeation studies of vismodegib through dermatomed porcine ear skin were conducted using vertical Franz diffusion cells. Skin irritation potential of vismodegib formulation was assessed using an in vitro reconstructed human epidermis model. Results of the in vitro permeation studies revealed significant enhancement in permeation of vismodegib through microneedle- treated skin. As the needle length increased from 500 to 1100 and 1400 mu m, drug delivery increased from 14.50 +/- 2.35 to 32.38 +/- 3.33 and 74.40 +/- 15.86 mu g/cm(2), respectively. Positive correlation between drug permeability and microneedle treatment duration was observed. The equilibration time was also found to affect the delivery of vismodegib. Thus, changes in microneedle length, equilibration time, and duration of treatment altered transdermal delivery of vismodegib.