Enhancement of topical 5-aminolaevulinic acid delivery by erbium:YAG laser and microdermabrasion: a comparison with iontophoresis and electroporation

J-Y. Fang

Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, Taoyuan 333, Taiwan*Department of Dermatology, Taipei Medical University Hospital and Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan
†Department of Dermatology, School of Medicine, Taipei Medical University, Taipei, Taiwan
‡Department of Dermatology, Taipei Municipal Wan Fang Hospital, Taipei, Taiwan

Search for more papers by this author

W-R. Lee,

W-R. Lee

Search for more papers by this author

S-C. Shen,

S-C. Shen

Search for more papers by this author

Y-P. Fang,

Y-P. Fang

Search for more papers by this author

C-H. Hu,

C-H. Hu

Search for more papers by this author

J-Y. Fang,

J-Y. Fang

Search for more papers by this author

W-R. Lee,

W-R. Lee

Search for more papers by this author

S-C. Shen,

S-C. Shen

Search for more papers by this author

Y-P. Fang,

Y-P. Fang

Search for more papers by this author

C-H. Hu,

C-H. Hu

Search for more papers by this author

First published: 29 June 2004

https://doi.org/10.1111/j.1365-2133.2004.06051.x

Citations: 113

Jia-You Fang.
E-mail: [email protected]

Share a link

Email
Wechat
Bluesky

Summary

Background 5-aminolaevulinic acid (ALA) is used as a protoporphyrin IX-precursor for the photodynamic therapy of superficial skin cancer and cutaneous metastases of internal malignancies. However, the permeability of hydrophilic ALA across the skin is very low.

Objectives and methods The objective of this study was to optimize and enhance the in vitro skin permeation of ALA by two resurfacing techniques: erbium:yttrium-aluminium-garnet (Erb:YAG) laser and microdermabrasion. Light microscopic changes in pig skin caused by these techniques were also compared. The electrically assisted methods, iontophoresis and electroporation, were also used to facilitate ALA permeation across laser- or microdermabrasion-treated skin.

Results Among the modalities tested in this study the Erb:YAG laser showed the greatest enhancement of ALA permeation. The laser fluence was found to play an important role in controlling the drug flux, producing enhancement ratios from 4-fold to 246-fold relative to the control. The skin permeation of ALA across microdermabrasion-treated skin was approximately 5–15-fold higher than that across intact skin. Both the ablated effect of the stratum corneum (SC) and ALA flux were proportional to the treatment duration of microdermabrasion. The application of iontophoresis or electroporation alone also increased the ALA permeation by approximately 15-fold and 2-fold, respectively. The incorporation of iontophoresis or electroporation with the resurfacing techniques caused a profound synergistic effect on ALA permeation.

Conclusions This basic study has encouraged the further investigation of ALA permeation by laser or microdermabrasion.

References

1 Rhodes LE, Tsoukas MM, Anderson RR, Kollias N. Iontophoretic delivery of ALA provides a quantitative model for ALA pharmacokinetics and PpIX phototoxicity in human skin. J Invest Dermatol 1997; 108: 87–91.
10.1111/1523-1747.ep12285644
CAS PubMed Web of Science® Google Scholar
2 Peng Q, Warloe T, Berg K et al. 5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future challenges. Cancer 1997; 79: 2282–308.
10.1002/(SICI)1097-0142(19970615)79:12<2282::AID-CNCR2>3.0.CO;2-O
CAS PubMed Web of Science® Google Scholar
3 Tsai JC, Chen IH, Wong TW, Lo YL. In vitro/in vivo correlations between transdermal delivery of 5-aminolevulinic acid and cutaneous protoporphyrin IX accumulation and effect of formulation. Br J Dermatol 2002; 146: 853–62.
10.1046/j.1365-2133.2002.04715.x
CAS PubMed Web of Science® Google Scholar
4 De Rosa FS, Bentley MVLB. Photodynamic therapy of skin cancers: sensitizers, clinical studies and future directives. Pharm Res 2000; 17: 1447–55.
10.1023/A:1007612905378
CAS PubMed Web of Science® Google Scholar
5 Manaloto RMP, Alster T. Erbium:YAG laser resurfacing for refractory melasma. Dermatol Surg 1999; 25: 121–3.
10.1046/j.1524-4725.1999.08103.x
CAS PubMed Web of Science® Google Scholar
6 Lloyd JR. The use of microdermabrasion for acne: a pilot study. Dermatol Surg 2001; 27: 329–31.
10.1046/j.1524-4725.2001.00313.x
CAS PubMed Web of Science® Google Scholar
7 Tsai RY, Wang CN, Chan HL. Aluminum oxide crystal microdermabrasion. A new technique for treating facial scarring. Dermatol Surg 1995; 21: 539–42.
10.1111/j.1524-4725.1995.tb00258.x
PubMed Web of Science® Google Scholar
8 Lopez RFV, Bentley MVLB, Delgado-Charro MB, Guy RH. Optimization of aminolevulinic acid delivery by iontophoresis. J Control Release 2003; 88: 65–70.
10.1016/S0168-3659(02)00456-X
CAS PubMed Web of Science® Google Scholar
9 Lee WR, Shen SC, Lai HH et al. Transdermal drug delivery enhanced and controlled by erbium:YAG laser: a comparative study of lipophilic and hydrophilic drugs. J Control Release 2001; 75: 155–66.
10.1016/S0168-3659(01)00391-1
CAS PubMed Web of Science® Google Scholar
10 Lee WR, Shen SC, Wang KH et al. The effect of laser treatment on skin to enhance and control transdermal delivery of 5-fluorouracil. J Pharm Sci 2002; 91: 1613–26.
10.1002/jps.10142
CAS PubMed Web of Science® Google Scholar
11 Fang JY, Fang CL, Sung KC, Chen HY. Effect of low frequency ultrasound on the in vitro percutaneous absorption of clobetasol 17-propionate. Int J Pharm 1999; 191: 33–42.
10.1016/S0378-5173(99)00230-6
CAS PubMed Web of Science® Google Scholar
12 Moser K, Kriwet K, Naik A et al. Passive skin penetration enhancement and its quantification in vitro. Eur J Pharm Biopharm 2001; 52: 103–12.
10.1016/S0939-6411(01)00166-7
CAS PubMed Web of Science® Google Scholar
13 Bunke A, Zerbe O, Schmid H et al. Degradation mechanism and stability of 5-aminolevulinic acid. J Pharm Sci 2000; 89: 1335–41.
10.1002/1520-6017(200010)89:10<1335::AID-JPS11>3.0.CO;2-#
CAS PubMed Web of Science® Google Scholar
14 Oishi H, Nomiyama H, Nomiyama K, Tomokuni K. Fluorometric HPLC determination of 5-aminolevulinic acid in the plasma and urine of lead workers: biological indicators of lead exposure. J Anal Toxicol 1996; 20: 106–10.
10.1093/jat/20.2.106
CAS PubMed Web of Science® Google Scholar
15 Lee S, Kollias N, McAuliffe DJ et al. Topical drug delivery in humans with a single photomechanical wave. Pharm Res 1999; 11: 1717–21.
10.1023/A:1018954015441
Web of Science® Google Scholar
16 Grevelink JM, Ross EV, Anderson RR. Lasers in dermatology. In: Fitzpatrick's Dermatology in General Medicine ( IM Freedberg, AZ Eisen, K Wolff, KF Austen, LA Goldsmith, SI Katz, TB Fitzpatrick, eds). New York: McGraw-Hill Health Professions Division, 1999.
Google Scholar
17 Polnikorn N, Goldberg DJ, Suwanchinda A, Ng SW. Erbium:YAG laser resurfacing in Asians. Dermatol Surg 1998; 24: 1303–7.
10.1111/j.1524-4725.1998.tb00004.x
CAS PubMed Web of Science® Google Scholar
18 Puliafito CA, Steinert RE. Short-pulsed Nd-YAG laser microsurgery of the eye. IEEE J Quant Elect 1984; 20: 1442–8.
10.1109/JQE.1984.1072343
Web of Science® Google Scholar
19 Nelson JS, McCullough JL, Glenn TC et al. Mid-infrared laser ablation of stratum corneum enhances in vitro percutaneous transport of drugs. J Invest Dermatol 1991; 97: 874–9.
10.1111/1523-1747.ep12491600
PubMed Web of Science® Google Scholar
20 Lopez RFV, Bentley MVLB, Delgado-Charro MB, Guy RH. Iontophoretic delivery of 5-aminolevulinic acid (ALA): effect of pH. Pharm Res 2001; 18: 311–15.
10.1023/A:1011050829531
CAS PubMed Web of Science® Google Scholar
21 Elfsson B, Wallin I, Eksborg S et al. Stability of 5-aminolevulinic acid in aqueous solution. Eur J Pharm Sci 1998; 7: 87–91.
10.1016/S0928-0987(98)00009-8
Web of Science® Google Scholar
22 Vanbever R, De Morre N, Préat V. Transdermal delivery of fentanyl by electroporation. II. Mechanisms involved in drug transport. Pharm Res 1996; 13: 1360–6.
10.1023/A:1016073917125
CAS PubMed Web of Science® Google Scholar
23 Moan J, Berg K, Gadmar O et al. The temperature dependence of protoporphyrin IX production in cells and tissues. Photochem Photobiol 1999; 70: 669–73.
10.1111/j.1751-1097.1999.tb08268.x
CAS PubMed Web of Science® Google Scholar
24 Lieb S, Szeimies R, Lee G. Self-adhesive thin films for topical delivery of 5-aminolevulinic acid. Eur J Pharm Biopharm 2002; 53: 99–106.
10.1016/S0939-6411(01)00193-X
CAS PubMed Web of Science® Google Scholar

Citing Literature

Volume151, Issue1

July 2004

Pages 132-140

Enhancement of topical 5-aminolaevulinic acid delivery by erbium:YAG laser and microdermabrasion: a comparison with iontophoresis and electroporation

Summary

References

Citing Literature

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

Enhancement of topical 5-aminolaevulinic acid delivery by erbium:YAG laser and microdermabrasion: a comparison with iontophoresis and electroporation

Summary

References

Citing Literature

References

Related

Information