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Risk assessment of excess drug and sunscreen absorption via skin with ablative fractional laser resurfacing

Optimization of the applied dose for postoperative care

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Abstract

The ablative fractional laser is a new modality used for surgical resurfacing. It is expected that laser treatment can generally deliver drugs into and across the skin, which is toxicologically relevant. The aim of this study was to establish skin absorption characteristics of antibiotics, sunscreens, and macromolecules via laser-treated skin and during postoperative periods. Nude mice were employed as the animal model. The skin received a single irradiation of a fractional CO2 laser, using fluences of 4–10 mJ with spot densities of 100–400 spots/cm2. In vitro skin permeation using Franz cells was performed. Levels of skin water loss and erythema were evaluated, and histological examinations with staining by hematoxylin and eosin, cyclooxygenase-2, and claudin-1 were carried out. Significant signs of erythema, edema, and scaling of the skin treated with the fractional laser were evident. Inflammatory infiltration and a reduction in tight junctions were also observed. Laser treatment at 6 mJ increased tetracycline and tretinoin fluxes by 70- and 9-fold, respectively. A higher fluence resulted in a greater tetracycline flux, but lower skin deposition. On the other hand, tretinoin skin deposition increased following an increase in the laser fluence. The fractional laser exhibited a negligible effect on modulating oxybenzone absorption. Dextrans with molecular weights of 4 and 10 kDa showed increased fluxes from 0.05 to 11.05 and 38.54 μg/cm2/h, respectively. The optimized drug dose for skin treated with the fractional laser was 1/70–1/60 of the regular dose. The skin histology and drug absorption had recovered to a normal status within 2–3 days. Our findings provide the first report on risk assessment of excessive skin absorption after fractional laser resurfacing.

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References

  1. Sarnoff DS (2011) A comparison of wound healing between a skin protectant ointment and a medical device topical emulsion after laser resurfacing of the perioral area. J Am Acad Dermatol 64:S36–S43

    Article  PubMed  Google Scholar 

  2. Sapijaszko MJA, Zachary CB (2002) Er:YAG laser skin resurfacing. Dermatol Clin 20:87–96

    PubMed  Google Scholar 

  3. Allemann IB, Kaufman J (2010) Fractional photothermolysis–an update. Lasers Med Sci 25:137–144

    Article  Google Scholar 

  4. Lee WR, Shen SC, Al-Suwayeh SA, Yang HH, Yuan CY, Fang JY (2011) Laser-assisted topical drug delivery by using a low-fluence fractional laser: imiquimod and macromolecules. J Control Release 153:240–248

    Article  PubMed  CAS  Google Scholar 

  5. Regan TD, Uebelhoer NS, Satter E, Ross EV (2010) Depth of tissue ablation and residual thermal damage caused by a pixilated 2,940-nm laser in a swine skin model. Lasers Surg Med 42:408–411

    Article  PubMed  Google Scholar 

  6. Carniol PJ, Harirchian S, Kelly E (2011) Fractional CO2 laser resurfacing. Facial Plast Surg Clin N Am 19:247–251

    Article  Google Scholar 

  7. Skovbølling Haak C, Illes M, Paasch U, Hædersdal M (2011) Histological evaluation of vertical laser channels from ablative fractional resurfacing: an ex vivo pig skin model. Lasers Med Sci 26:465–471

    Article  PubMed  Google Scholar 

  8. Pan TL, Wang PW, Lee WR, Fang CL, Chen CC, Huang CM, Fang JY (2010) Systematic evaluations of skin damage irradiated by an erbium:YAG laser: histopathologic analysis, proteomic profiles, and cellular response. J Dermatol Sci 58:8–18

    Article  PubMed  CAS  Google Scholar 

  9. Lee WR, Shen SC, Al-Suwayeh SA, Li YC, Fang JY (2012) Erbium:YAG laser resurfacing increases skin permeability and the risk of excessive absorption of antibiotics and sunscreens: the influence of skin recovery on drug absorption. Toxicol Lett 211:150–158

    Article  PubMed  CAS  Google Scholar 

  10. Chiu TM, Huang CC, Lin TJ, Fang JY, Wu NL, Hung CF (2009) In vitro and in vivo anti-photoaging effects of an isoflavone extract from soybean cake. J Ethnopharmacol 126:108–113

    Article  PubMed  CAS  Google Scholar 

  11. Yuki T, Haratake A, Koishikawa H, Morita K, Miyachi Y, Inoue S (2007) Tight junction proteins in keratinocytes: localization and contribution to barrier function. Exp Dermatol 16:324–330

    Article  PubMed  CAS  Google Scholar 

  12. Yamashita N, Tachibana K, Ogawa K, Tsujita N, Tomita A (1997) Scanning electron microscopic evaluation of the skin surface after ultrasound exposure. Anat Res 247:455–461

    Article  CAS  Google Scholar 

  13. Lee WR, Shen SC, Pai MH, Yang HH, Yuan CY, Fang JY (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 145:124–133

    Article  PubMed  CAS  Google Scholar 

  14. Sloan KB, Wasdo S (2003) Designing for topical delivery: prodrugs can make the difference. Med Res Rev 23:763–793

    Article  PubMed  CAS  Google Scholar 

  15. Benson HAE, Sarveiya V, Risk S, Roberts MS (2005) Influence of anatomical site and topical formulation on skin penetration of sunscreens. Ther Clin Risk Manag 1:209–218

    PubMed  CAS  Google Scholar 

  16. Otulakowski G, Zhou L, Fang-Leung WP, Gendimenico GJ, Samuel SES, Lau CY (1994) Use of a human skin-grafted nude mouse model for the evaluation of topical retinoic acid treatment. J Invest Dermatol 102:515–518

    Article  PubMed  CAS  Google Scholar 

  17. Alvarez-Román R, Naik A, Kalia YN, Fessi H, Guy RH (2004) Visualization of skin penetration using confocal laser scanning microscopy. Eur J Pharm Biopharm 58:301–316

    Article  PubMed  Google Scholar 

  18. Hada N, Hasegawa T, Takahashi H, Ishibashi T, Sugibayashi K (2005) Cultured skin loaded with tetracycline HCl and chloramphenicol as dermal delivery system: mathematical evaluation of the cultured skin containing antibiotics. J Control Release 108:341–350

    Article  PubMed  CAS  Google Scholar 

  19. Ishikawa C, Tsuda T, Konishi H, Nakagawa N, Yamanishi K (2009) Tetracyclines modulate protease-activated receptor 2-mediated proinflammatory reactions in epidermal keratinocytes. Antimicrob Agents Chemother 53:1760–1765

    Article  PubMed  CAS  Google Scholar 

  20. Lee S, McAuliffe DJ, Flotte TJ, Kollias N, Doukas AG (2001) Photomechanical transdermal delivery: the effect of laser confinement. Lasers Surg Med 28:344–347

    Article  PubMed  CAS  Google Scholar 

  21. Ourique AF, Melero A, de Bona da Silva C, Schaefer UF, Pohlmann AR, Guterres SS, Lehr CM, Kostka KH, Beck RCR (2011) Improved photostability and reduced skin permeation of tretinoin: development of a semisolid nanomedicine. Eur J Pharm Biopharm 79:95–101

    Article  PubMed  CAS  Google Scholar 

  22. García-Fernández RA, Pérez-Martínez C, Espinosa-Álvarez J, García-Iglesias MJ (2007) In vivo long-term effects of retinoic acid exposure in utero on induced hyperplastic epidermal foci in murine skin. Vet Dermatol 18:287–293

    Article  PubMed  Google Scholar 

  23. Goldberg DJ, Berlin AL, Phelps R (2008) Histologic and ultrastructural analysis of melasma after fractional resurfacing. Lasers Surg Med 40:134–138

    Article  PubMed  Google Scholar 

  24. Togsverd-Bo K, Haak CS, Thaysen-Peterson D, Wulf HC, Anderson RR, Hædersdal M (2012) Intensified photodynamic therapy of actinic keratoses with fractional CO2 laser: a randomized clinical trial. Br J Dermatol 166:1262–1269

    Article  PubMed  CAS  Google Scholar 

  25. Fu JJJ, Hillebrand GG, Raleigh P, Li J, Marmor MJ, Bertucci V, Grimes PE, Mandy SH, Perez MI, Weinkle SH, Kaczvinsky JR (2010) A randomized, controlled comparative study of the wrinkle reduction benefits of a cosmetic niacinamide/peptide/retinyl propionate product regimen vs. a prescription 0.02 % tretinoin product regimen. Br J Dermatol 162:647–654

    Article  PubMed  CAS  Google Scholar 

  26. Duerbeck NB, Dowling DD (2012) Vitamin A: too much of a good thing? Obstet Gynecol Surv 67:122–128

    Article  PubMed  Google Scholar 

  27. Cross SE, Jiang R, Benson HAE, Roberts MS (2001) Can increasing the viscosity of formulations be used to reduce the human skin penetration of the sunscreen oxybenzone? J Invest Dermatol 117:147–150

    Article  PubMed  CAS  Google Scholar 

  28. Benson HAE (2000) Assessment and clinical implications of absorption of sunscreens across skin. Am J Clin Dermatol 1:217–224

    Article  PubMed  CAS  Google Scholar 

  29. Kasichayanula S, House JD, Wang T, Gu X (2007) Percutaneous characterization of the insect repellent DEET and the sunscreen oxybenzone from topical skin application. Toxicol Appl Pharmacol 223:187–194

    Article  PubMed  CAS  Google Scholar 

  30. Yang HS, Shin J, Bhang SH, Shin JY, Park J, Im GI, Kim CS, Kim BS (2011) Enhanced skin wound healing by a sustained release of growth factors contained in platelet-rich plasma. Exp Mol Med 43:622–629

    Article  PubMed  CAS  Google Scholar 

  31. Shin MK, Lee JH, Lee SJ, Kim NI (2012) Platelet-rich plasma combined with fractional laser therapy for skin rejuvenation. Dermatol Surg 38:623–630

    Article  PubMed  CAS  Google Scholar 

  32. Cao D, Kitamura T, Todo H, Yoo SD, Sugibayashi K (2008) Pretreatment effects of moxibustion on the skin permeation of FITC-dextran. Int J Pharm 354:117–125

    Article  PubMed  CAS  Google Scholar 

  33. Kim YC, Late S, Banga AK, Ludovice PJ, Prausnitz MR (2008) Biochemical enhancement of transdermal delivery with magainin peptide: modification of electrostatic interactions by changing pH. Int J Pharm 362:20–28

    Article  PubMed  CAS  Google Scholar 

  34. Wu XM, Todo H, Sugibayashi K (2006) Effects of pretreatment of needle puncture and sandpaper abrasion on the in vitro skin permeation of fluorescein isothiocyanate (FITC)-dextran. Int J Pharm 316:102–108

    Article  PubMed  CAS  Google Scholar 

  35. Lee WR, Shen SC, Liu CJ, Fang CL, Hu CH, Fang JY (2006) Erbium:YAG laser-mediated oligonucleotide and DNA delivery via the skin: an animal study. J Control Release 115:344–353

    Article  PubMed  CAS  Google Scholar 

  36. Lee S, McAuliffe DJ, Kollias N, Flotte TJ, Doukas AG (2001) Permeabilization and recovery of the stratum corneum in vivo: the synergy of photomechanical waves and sodium lauryl sulfate. Lasers Surg Med 29:145–150

    Article  PubMed  CAS  Google Scholar 

  37. Honma Y, Arai I, Sakurai T, Futaki N, Hashimoto Y, Sugimoto M, Nakanishi Y, Nakaike S (2006) Effects of indomethacin and dexamethasone on mechanical scratching-induced cutaneous barrier disruption in mice. Exp Dermatol 15:501–508

    Article  PubMed  CAS  Google Scholar 

  38. Hantash BM, Bedi VP, Chan KF, Zachary CB (2007) Ex vivo histological characterization of a novel ablative fractional resurfacing device. Lasers Surg Med 39:87–95

    Article  PubMed  Google Scholar 

  39. Zhang LW, Al-Suwayeh SA, Hsieh PW, Fang JY (2010) A comparison of skin delivery of ferulic acid and its derivatives: evaluation of their efficacy and safety. Int J Pharm 399:44–51

    Article  PubMed  CAS  Google Scholar 

  40. Chan HHL, Mainstein D, Yu CS, Shek S, Kono T, Wei WI (2007) The prevalence and risk factors of post-inflammatory hyperpigmentation after fractional resurfacing in Asians. Lasers Surg Med 39:381–385

    Article  PubMed  Google Scholar 

  41. Wilgus TA, Bergdall VK, Tober KL, Hill KJ, Mitra S, Flavahan NA, Oberyszyn TM (2004) The impact of cyclooxygenase-2 mediated on scarless fetal wound healing. Am J Pathol 165:753–761

    Article  PubMed  CAS  Google Scholar 

  42. Peltonen S, Riehokainen J, Pummi K, Peltonen J (2007) Tight junction components occludin, ZO-1, and claudin-1, -4, and -5 in active and healing psoriasis. Br J Dermatol 156:466–472

    Article  PubMed  CAS  Google Scholar 

  43. Kirschner N, Houdek P, Fromm M, Moll I, Brandner JM (2010) Tight junctions form a barrier in human epidermis. Eur J Cell Biol 89:839–842

    Article  PubMed  CAS  Google Scholar 

  44. Niessen CM (2007) Tight junctions/adherens junctions: basic structure and function. J Invest Dermatol 127:2525–2532

    Article  PubMed  CAS  Google Scholar 

  45. Fang JY, Fang CL, Liu CH, Su YH (2008) Lipid nanoparticles as vehicles for topical psoralen delivery: solid lipid nanoparticles (SLN) versus nanostructured lipid carriers (NLC). Eur J Pharm Biopharm 70:633–640

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Jia-You Fang.

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Chen, WY., Fang, CL., Al-Suwayeh, S.A. et al. Risk assessment of excess drug and sunscreen absorption via skin with ablative fractional laser resurfacing. Lasers Med Sci 28, 1363–1374 (2013). https://doi.org/10.1007/s10103-012-1257-2

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  • DOI: https://doi.org/10.1007/s10103-012-1257-2

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