Curtin Medical School, Curtin University, Perth, Western Australia, Australia.
Future Industries Institute, University of South Australia, Adelaide, Australia.
Int J Pharm. 2021 Dec 15;610:121258. doi: 10.1016/j.ijpharm.2021.121258. Epub 2021 Nov 2.
Physical drug delivery enhancement in skin has been shown to enhance cosmeceutical actives efficacy. Among the physical drug delivery enhancement technologies, microneedle is the most commercially successful technology. However, there are pros and cons like other physical enhancement technologies including variabilities in penetration depth and lack of efficacy. In this study, three physical topical dug delivery enhancements, elongated microparticles, microneedles and dermaroller, were applied to ex vivo pig skin and compared. The model topical drug that was used is 5-Aminolevulinic acid, the most commonly used photosensitiser prodrug. The skin was pre-treated before mounting on to Franz cell diffusion apparatus. Transdermal epidermal water loss was measured, and receptor fluids were collected at 7 time points for HPLC analysis. The results show that all three technologies disrupted the skin surface. All microporation pre-treatments significantly enhanced mALA cumulative permeation over 8 h (p < 0.001), with the 24x dermaroller significantly greater than 12x dermaroller (p < 0.001) and both dermaroller treatments significantly greater than microneedles and elongated microparticles (p < 0.05). The microporation pre-treatments all significantly increased mALA deposition in the stratum corneum and deeper skin tissues compared to passive administration, with deposition increases ranging from 3.6x to 15.1x that of passive administration. The DR pretreatment showed highest enhancement ratios (amount 5-Aminolevulinic acid in skin at 8 h following pretreatment v passive) with the following order of enhancement: 24x dermaroller > 12x dermaroller > microneedles > elongated microparticles. In conclusion, physical enhancement tools such as microneedles, dermarollers and elongated microparticles demonstrated significant penetration and retention of mALA through/into piglet skin. Further study is needed to determine the cost, dose and patient compliance.
物理药物输送增强技术已被证明可以提高化妆品功效。在物理药物输送增强技术中，微针是最成功的商业技术。然而，像其他物理增强技术一样，它也有优缺点，包括渗透深度的可变性和缺乏疗效。在这项研究中，三种物理局部药物输送增强技术，即长型微粒、微针和微针滚轮，应用于离体猪皮进行了比较。所使用的模型局部药物是 5-氨基酮戊酸，最常用的光增敏前药。在将皮肤安装到 Franz 细胞扩散装置之前，对其进行预处理。测量经皮表皮水分损失，并在 7 个时间点收集受体液进行 HPLC 分析。结果表明，所有三种技术都破坏了皮肤表面。所有微穿孔预处理均显著增加了 mALA 在 8 小时内的累积渗透量（p<0.001），24 倍微针滚轮显著大于 12 倍微针滚轮（p<0.001），且两种微针滚轮处理均显著大于微针和长型微粒（p<0.05）。与被动给药相比，微穿孔预处理均显著增加了 mALA 在角质层和更深皮肤组织中的沉积，沉积增加幅度从 3.6 倍到 15.1 倍不等。与被动给药相比，DR 预处理显示出最高的增强比（预处理后 8 小时皮肤中 5-氨基酮戊酸的量），增强比的顺序为：24 倍微针滚轮>12 倍微针滚轮>微针>长型微粒。总之，微针、微针滚轮和长型微粒等物理增强工具显著提高了 mALA 通过/进入小猪皮的渗透和保留。需要进一步研究以确定成本、剂量和患者依从性。
