Comparison of physical enhancement technologies in the skin permeation of methyl amino levulinic acid (mALA).

ABSTRACT

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.