Microneedle Pre-treatment of Human Skin Improves 5-Aminolevulininc Acid (ALA)- and 5-Aminolevulinic Acid Methyl Ester (MAL)-Induced PpIX Production for Topical Photodynamic Therapy Without Increase in Pain or Erythema
To determine the impact of skin pretreatment with microneedles (MNs) on ALA- and MAL-induced protoporphyrin IX (PpIX) production, as well as MN impact on pain sensations during light exposure and erythema after PDT.
The skin of 14 healthy volunteers was preteated with MNs. Equal amounts of creams containing 2%, 8% and 16% (w/w) ALA and MAL were applied on 1 cm2 areas for 4 h. Additionally, 16% ALA and MAL creams were applied for 24 h. Afterwards, PpIX fluorescence spectra were measured. Sixteen percent ALA and MAL spots were exposed to red light (632 nm, 77 mW/cm2). Time for pain to occur was measured in seconds, and erythemal response was monitored up to 6 h after the end of the light exposure.
Use of MNs increased the PpIX fluorescence after 4 h incubation time with 2% and 8% ALA or MAL, but not with 16% ALA or MAL. Pretreatment with MNs did not increase the pain sensations during light exposure, nor did it influence erythema occurrence.
MNs are a promising tool for improving the efficiency of topical PDT by improving the cutaneous delivery of ALA and MAL, without increase in side effects.
KEY WORDSaminolevulinic acid (ALA) aminolevulinic acid methyl ester (MAL) erythema microneedles (MNs) photodynamic therapy (PDT)
- 5.Rossi R, Bruscino N, Ricceri F, Grazzini M, Dindelli M, Lotti T. Photodynamic treatment for viral infections of the skin. Ital Dermatol Venereol. 2009;144:79–83.Google Scholar
- 7.Yin R, Hao F, Deng J, Yang XC, Yan H. Investigation of optimal ALA concentration applied in topical ALA-PDT for treatment of moderate to severe acne: a pilot study on Chinese people. Br J Dermatol. 2010; doi:10.1111/j.1365-2133.2010.09860.
- 8.Gholam P, Denk K, Sehr T, Enk A, Hartmann M. Factors influencing pain intensity during topical photodynamic therapy of complete cosmetic units for actinic keratoses. J Am Acad Dermatol. 2010;63:213–8.Google Scholar
- 9.Arits AH, van de Weert MM, Nelemans PJ, Kelleners-Smeets NW. Pain during topical photodynamic therapy: uncomfortable and unpredictable. J Eur Acad Dermatol Venereol 2010; doi:10.1111/j.1468-3083.2010.03670.
- 11.van den Akker JT, Iani V, Star WM, Sterenborg HJ, Moan J. Topical application of 5-aminolevulinic acid hexyl ester and 5-aminolevulinic acid to normal nude mouse skin: differences in protoporphyrin IX fluorescence kinetics and the role of the stratum corneum. Photochem Photobiol. 2000;72:681–9.CrossRefPubMedGoogle Scholar
- 17.Donnelly RF, Morrow DIJ, McCarron PA, et al. Microneedle-mediated intradermal delivery of 5-aminolevulinic acid: potential for enhanced topical photodynamic therapy. J Control Release 2008;129:154–62.Google Scholar
- 18.Donnelly RF, Cassidy CM, Loughlin RG, et al. Delivery of methylene blue and meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate from cross-linked poly(vinyl alcohol) hydrogels: a potential means of photodynamic therapy of infected wounds. J Photochem Photobiol B. 2009;96:223–31.CrossRefPubMedGoogle Scholar
- 20.Donnelly RF, Singh TR., Tunney MM, et al. Microneedle arrays allow lower microbial penetration than hypodermic needles in vitro. Pharm Res. 2009;26:2513–22.Google Scholar
- 26.Lee JW, Yoo KH, Kim BJ, Kim MN. Photodynamic therapy with methyl 5-aminolevulinate acid combined with microneedle treatment in patients with extensive alopecia areata. Clin Exp Dermatol. 2010;35:548–9.Google Scholar
- 28.Donnelly RF, Majithiya R, Thakur RRS, et al. Design, optimization and characterisation of polymeric microneedle arrays prepared by a novel laser-based micromoulding technique. Pharm Res. 2009; doi:10.1007/s11095-010-0169-8.
- 29.Moriyama EM, Kim A, Bogaards A, Lilge L, Wilson BCA. Ratiometric fluorescence imaging system for surgical guidance. Adv Opt Tech. 2008;2008:1–10.Google Scholar
- 37.Busch TM. Local physiological changes during photodynamic therapy. Lasers Surg Med. 2006;38:494–9.Google Scholar