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 1800mm. Needling was done by tapping the skin vertically from 5cm high above quickly. AFR was performed with a 10.6mm wavelength prototype CO2 laser, using stacked single pulses of 3 millisecond and 91.6mJ 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 70mm thin layer of thermally coagulated dermis, respectively. The cone is approximately 200mm in diameter at the opening and 1850mm in depth. Plum blossom needle created irregular cone shaped channels of approximately 180mm 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 100mm far from the hole (P=0.000) versus AFR followed by ALA application at skin depths of 120 and 500mm. Needling after ALA application presented higher porphyrin fluorescence at the edge of hole at skin depths of 120mm (P<0.005) and lower porphyrin fluorescence at 1000mm deep hole edge, and 100mm far from the hole at 120mm, 500mm and 1000mm 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.
Photodiagnosis and photodynamic therapy