title: Plum-blossom needling promoted PpIX fluorescence intensity from 5-aminolevulinic acid in porcine skin model and patients with actnic keratosis.
abstract: OBJECTIVE
  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.
  
  
  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 1800μm. Needling was done by tapping the skin vertically from 5cm high above quickly. AFR was performed with a 10.6μm 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 70μm thin layer of thermally coagulated dermis, respectively. The cone is approximately 200μm in diameter at the opening and 1850μm in depth. Plum-blossom needle created irregular cone-shaped channels of approximately 180μm 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 100μm far from the hole (P=0.000) versus AFR followed by ALA application at skin depths of 120 and 500μm. Needling after ALA application presented higher porphyrin fluorescence at the edge of hole at skin depths of 120μm (P<0.005) and lower porphyrin fluorescence at 1000μm deep hole edge, and 100μm far from the hole at 120μm, 500μm and 1000μm 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.
authors.affiliation: Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University, Shanghai, PR China. Electronic address: chenjia_doc@163.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University, Shanghai, PR China. Electronic address: Yunfeng0519116@aliyun.com.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University, Shanghai, PR China. Electronic address: wpeiru@gmail.com.
authors.forename: Peiru
authors.initials: P
authors.lastname: Wang
authors.affiliation: Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University, Shanghai, PR China. Electronic address: bowang_shcn@hotmail.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University, Shanghai, PR China. Electronic address: zglamu@163.com.
authors.forename: Guolong
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University, Shanghai, PR China. Electronic address: Wangxiuli20150315@163.com.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wang
mesh_terms: D015670:Acupuncture Therapy / Q000295:instrumentation / Q000379:methods*; D000368:Aged; D000622:Aminolevulinic Acid / Q000493:pharmacokinetics*; D000818:Animals; D005260:Female; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D055623:Keratosis, Actinic / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods; D008875:Middle Aged; D017319:Photosensitizing Agents / Q000493:pharmacokinetics; D011524:Protoporphyrins / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D012869:Skin Absorption / Q000502:physiology*; D013552:Swine
chemical_list: D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX
keywords: Fractional ablative resurfacing; Photodynamic therapy; Photosensitizer; Plum-blossom needling; Topical drugs