Plum-blossom needling promoted PpIX fluorescence intensity from 5-aminolevulinic acid in porcine skin model and patients with actnic keratosis

Background and objectives: Plum-blossom needling might enhance transdermal penetration of topically applied drugs by creating vertical channels. The purpose of this study was to evaluate drug delivery assisted by plum-blossom needling comparing with CO2 laser ablative fractional resurfacing (AFR) using 5-aminolevulinic acid (5-ALA), a porphyrin precursor, as a test drug. Materials and methods: Ex vivo porcine skin was treated with plum-blossom needle(HWATO, Suzhou medical supplies factory Co., Ltd. China) or CO2 laser AFR before topical application of 20% 5-ALA(Sigma-Aldrich, Co., USA)cream, placebo cream and no cream. ALA-induced porphyrin fluorescence was measured by fluorescence microscopy at skin depths down to 1800 mu m. Needling was done by tapping the skin vertically from 5 cm high above quickly. AFR was performed with a 10.6 mu m wavelength prototype CO2 laser, using stacked single pulses of 3 millisecond and 91.6 mJ per pulse. Plum-blossom needling after ALA application was also done. Fluorescence intensity on lesion surface was examined by curalux spectrum analyzer (Laser Institute of Munich University, Germany) and VAS pain score was recorded in a randomized split-lesion clinical trial including 6 patients, 8 actinic keratosis lesions. Results: AFR created regular cone-shaped channels surrounded by a 70 mu m thin layer of thermally coagulated dermis, respectively. The cone is approximately 200 mu m in diameter at the opening and 1850 mu m in depth. Plum-blossom needle created irregular cone-shaped channels of approximately 180 mu m in diameter at the opening and it always drags a tail which was shaped from the closed deeper channels. There was no porphyrin fluorescence in placebo cream or untreated skin sites. Plum-blossom needling followed by ALA application enhanced drug delivery with significantly higher porphyrin fluorescence at the edge of hole (P< 0.005) and 100 mu m far from the hole (P= 0.000) versus AFR followed by ALA application at skin depths of 120 and 500 mu m. Needling after ALA application presented higher porphyrin fluorescence at the edge of hole at skin depths of 120 mu m (P< 0.005) and lower porphyrin fluorescence at 1000 mu m deep hole edge, and 100 mu m far from the hole at 120 mu m, 500 mu m and 1000 mu m depths versus AFR followed by ALA application (P< 0.005). Skin massage after ALA application did not affect ALA-induced porphyrin fluorescence after pretreatment of plum-blossom needling or AFR. ALA application after plum-blossom needling was better than before plum-blossom needling. The clinical trial showed that the surface fluorescence intensity was stronger in needle-pretreated-lesion than in laser-pretreated-lesion. While the VAS pain score between needle treatment and laser treatment was almost the same. Conclusions: Plum-blossom needling facilitates delivery of topical ALA into the dermis. It may help ALA to diffuse a little more broadly than AFR does in superficial dermis and obtain similar clinical effect with a much lower cost. Plum-blossom needling treatment appears to be a clinically practical and economical means for enhancing transdermal delivery of ALA, a photodynamic therapy drug, and presumably many other topical skin medications. (C) 2016 Elsevier B.V. All rights reserved.