Ablative fractional laser alters biodistribution of ingenol mebutate in the skin

详细信息    查看全文

• 作者：A. M. Erlendsson ; E. H. Taudorf ; A. H. Eriksson…
• 关键词：Ablative fractional laser ; Laser ; Laser ; assisted drug delivery ; Drug delivery ; Ingenol mebutate ; Biodistribution ; Non ; melanoma skin cancer ; Actinic keratosis
• 刊名：Archives of Dermatological Research
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：307
• 期：6
• 页码：515-522
• 全文大小：843 KB
• 参考文献：1.Bachhav YG, Heinrich A, Kalia YN (2011) Using laser microporation to improve transdermal delivery of diclofenac: increasing bioavailability and the range of therapeutic applications. Eur J Pharm Biopharm 78:408-14PubMed View Article
  2.Bachhav YG, Summer S, Heinrich A, Bragagna T, B?hler C, Kalia YN (2010) Effect of controlled laser microporation on drug transport kinetics into and across the skin. J Control Release 146:31-6PubMed View Article
  3.Bloom BS, Brauer JA, Geronemus RG (2013) Ablative fractional resurfacing in topical drug delivery: an update and outlook. Dermatol Surg 39:839-48PubMed View Article
  4.Brown MB, Martin GP, Jones SA, Akomeah FK (2006) Dermal and transdermal drug delivery systems: current and future prospects. Drug Deliv 13:175-87PubMed View Article
  5.Elias PM, Menon GK (1991) Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res 24:1-6PubMed
  6.Ersvaer E, Kittang AO, Hampson P, Sand K, Gjertsen BT, Lord JM, Bruserud O (2010) The protein kinase C agonist PEP005 (ingenol 3-angelate) in the treatment of human cancer: a balance between efficacy and toxicity. Toxins (Basel) 2:174-94View Article
  7.Franz TJ (1975) Percutaneous absorption on the relevance of in vitro data. J Invest Dermatol 64:190-95PubMed View Article
  8.Franz TJ (1983) Kinetics of cutaneous drug penetration. Int J Dermatol 22:499-05PubMed View Article
  9.Haak CS, Bhayana B, Farinelli WA, Anderson RR, Haedersdal M (2012) The impact of treatment density and molecular weight for fractional laser-assisted drug delivery. J Control Release 163:335-41PubMed View Article
  10.Haak CS, Farinelli WA, Tam J, Doukas AG, Anderson RR, Haedersdal M (2012) Fractional laser-assisted delivery of methyl aminolevulinate: impact of laser channel depth and incubation time. Lasers Surg Med 44:787-95PubMed View Article
  11.Haedersdal M, Katsnelson J, Sakamoto FH, Farinelli WA, Doukas AG, Tam J, Anderson RR (2011) Enhanced uptake and photoactivation of topical methyl aminolevulinate after fractional CO2 laser pretreatment. Lasers Surg Med 43:804-13PubMed View Article
  12.Haedersdal M, Sakamoto FH, Farinelli WA, Doukas AG, Tam J, Anderson RR (2010) Fractional CO(2) laser-assisted drug delivery. Lasers Surg Med 42:113-22PubMed View Article
  13.Kedei N, Lundberg DJ, Toth A, Welburn P, Garfield SH, Blumberg PM (2004) Characterization of the interaction of ingenol 3-angelate with protein kinase C. Cancer Res 64:3243-255PubMed View Article
  14.Lebwohl M, Swanson N, Anderson LL, Melgaard A, Xu Z, Berman B (2012) Ingenol mebutate gel for actinic keratosis. N Engl J Med 366:1010-019PubMed View Article
  15.Lee W-R, Shen S-C, Al-Suwayeh SA, Yang H-H, Li Y-C, Fang J-Y (2013) Skin permeation of small-molecule drugs, macromolecules, and nanoparticles mediated by a fractional carbon dioxide laser: the role of hair follicles. Pharm Res 30:792-02PubMed View Article
  16.Lee W-R, Shen S-C, Al-Suwayeh SA, Yang H-H, Yuan C-Y, Fang J-Y (2011) Laser-assisted topical drug delivery by using a low-fluence fractional laser: imiquimod and macromolecules. J Control Release 153:240-48. doi:10.-016/?j.?jconrel.-011.-3.-15 PubMed View Article
  17.Lee W-R, Shen S-C, Pai M-H, Yang H-H, Yuan C-Y, Fang J-Y (2010) Fractional laser as a tool to enhance the skin permeation of 5-aminolevulinic acid with minimal skin disruption: a comparison with conventional erbium:YAG laser. J Control Release 14:124-33View Article
  18.LEO Pharma A/S (2012) Product information picato gel. 1-
  19.Li L, Shukla S, Lee A, Garfield SH, Maloney DJ, Ambudkar SV, Yuspa SH (2010) The skin cancer chemotherapeutic agent ingenol-3-angelate (PEP005) is a substrate for the epidermal multidrug transporter (ABCB1) and targets tumor vasculature. Cancer Res 70:4509-519PubMed Central PubMed View Article
  20.Manstein D, Herron GS, Sink RK, Tanner H, Anderson RR (2004) Fractional photothermolysis: a new concept for cutaneous remodeling using microscopic patterns of thermal injury. Lasers Surg Med 34:426-38PubMed View Article
  21.Nino M, Calabrò G, Santoianni P (2010) Topical delivery of active principles : the field of dermatological research. Dermatol Online J 16(1):4PubMed
  22.Paasch U, Haedersdal M (2011) Laser systems for ablative fractional resurfacing. Expert Rev Med Devices 8:67-3PubMed View Article
  23.Siller G, Rosen R, Freeman M, Welburn P, Katsamas J, Ogbourne SM (2010) PEP005 (ingenol mebutate) gel for the topical treatment of superficial basal cell carcinoma: results of a randomized phase IIa trial. Australas J Dermatol 51:99-05PubMed View Article
  24.Stahlhut M, Bertelsen M, H?yer-Hansen M, Svendsen N, Eriksson AH, Lord JM, Scheel-Toellner D, Young SP, Zibert JR (2012) Ingenol mebutate-induced cell death patterns in normal and cancer epithelial cells. J Drugs Dermatol 11:1181-192PubMed
  25.Taudorf EH, Haak CS, Erlendsson AM, Philipsen PA, Anderson RR, Paasch U, Haeder
• 作者单位：A. M. Erlendsson (1) (2)
  E. H. Taudorf (1)
  A. H. Eriksson (3)
  C. S. Haak (1) (2)
  J. R. Zibert (3)
  U. Paasch (4)
  R. R. Anderson (2)
  M. Haedersdal (1) (2)
  
  1. Department of Dermatology, Bispebjerg University Hospital, Copenhagen University, Copenhagen, Denmark
  2. Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  3. LEO Pharma A/S, Ballerup, Denmark
  4. Department of Dermatology, Venerology, and Allergology, University of Leipzig, Leipzig, Germany
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Dermatology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-069X

文摘

Topically applied ingenol mebutate (IngMeb) is approved for field-treatment of actinic keratosis and is currently being investigated for treatment of non-melanoma skin cancer (NMSC). Ablative fractional lasers (AFXLs) generate microscopic ablation zones (MAZs) in the skin, which may help induce a deep penetration needed for effective treatment of NMSC. Using Franz diffusion cells, uptake and bio-distribution were investigated over 21?h in intact (n?=?9) and AFXL-exposed porcine skin (n?=?58). A 2940-nm fractional Er:YAG laser generated intraepidermal (11.2?mJ/MAZ; 66?μm deep, 177?μm wide) and intradermal (128?mJ/MAZ; 570?μm deep, 262 wide) MAZ’s with 16, 97, and 195?MAZs/cm2. Surface ablation densities corresponded to 0.5, 2.5, and 5?% for intraepidermal MAZs, and corresponded to 1, 5, and 10.5?% for intradermal MAZs. Liquid-chromatography–mass-spectrometry quantified deposition of IngMeb in stratum corneum, epidermis, dermis, and receiver chamber. In intact skin, IngMeb readily penetrated to the epidermal layer (1,314?ng, 41?% of the applied IngMeb), while dermal deposition was limited (508?ng, 16?%). In AFXL-exposed skin, a profound dermal deposition of IngMeb was achieved, while less accumulated in SC and epidermis. Uptake depended entirely on laser density; increasing coverage from 0?% to 0.5?%, 1?%, 2.5?%, 5?%, and 10.5?% enhanced dermal uptake 1.6-, 2.1-, 3.1-, 3.4-, and 3.9-fold, respectively (p?<?0.0001). Channel depth did not influence drug uptake; at 5?% density, dermal deposition with intraepidermal and intradermal MAZs was analogous (1801 vs. 1744; p?=?0.447). In conclusion, IngMeb readily distributes to superficial layers of intact skin, whereas dermal uptake is limited. Independent of channel depth, AFXL enhances dermal drug deposition, providing for customized topical delivery and potential use of IngMeb for treatment of NMSC.