In vitro percutaneous absorption and in vivo protoporphyrin IX accumulation in skin and tumors after topical 5-aminolevulinic acid application with enhancement using an erbium: YAG laser

Shing Chuan Shen, Woan Ruoh Lee, Yi Ping Fang, Jun-Hung Hu, Jia You Fang

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

5-Aminolevulinic acid (ALA) is used as a precursor of protoporphyrin IX (PpIX) for photodynamic therapy (PDT) of superficial skin cancers and subcutaneous metastases of internal malignancies. The permeability of ALA across intact skin is always low, making it difficult to achieve the desired therapeutic benefits. Hence new methods for enhancing ALA permeation are urgently needed. The aim of this study was to determine the in vivo kinetics of PpIX generation in mouse tissues after topical ALA application enhanced by an erbium (Er):yttrium-aluminum-garnet (YAG) laser. The in vitro permeation of ALA was also used to screen the optimal method for the in vivo study. The efficacy of the improved drug delivery was determined as a function of various laser fluences and cancer models. ALA applied to laser-treated skin produced a higher accumulations of PpIX within superficial skin and subcutaneous tumors as compared to those of the non-treated group (t-test, p <0.05). The enhancement ratios (ER) of laser-treated skin ranged from 1.7 to 4.9 times as compared to the control depending to the fluences used. The enhanced PpIX level of laser-treated skin was generally more pronounced in normal and lesional skin than in subcutaneous nodular tumors. Confocal laser scanning microscopy (CLSM) of laser-treated skin revealed intense red fluorescence within the epidermis and upper dermis, and a much-weaker fluorescence within the bottom layers of the skin. On the other hand, the fluorescence intensity of the control group was much lower than that of laser-treated group. The barrier properties of the skin irradiated by the laser had completely recovered within 3 days. Pretreatment of skin using an Er:YAG laser was useful in increasing the amount of Pp IX within skin tumors.

Original languageEnglish
Pages (from-to)929-938
Number of pages10
JournalJournal of Pharmaceutical Sciences
Volume95
Issue number4
DOIs
Publication statusPublished - Apr 2006

Fingerprint

Erbium
Skin Absorption
Aminolevulinic Acid
Solid-State Lasers
Tumors
Skin
Lasers
Neoplasms
Fluorescence
Permeation
protoporphyrin IX
In Vitro Techniques
yttrium-aluminum-garnet
Photodynamic therapy
Photochemotherapy
Skin Neoplasms
Dermis
Epidermis
Confocal Microscopy
Drug delivery

Keywords

  • 5-Aminolevulinic acid
  • Er:YAG laser
  • In vivo
  • Photodynamic therapy
  • Skin

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science

Cite this

@article{cc36348433114fe9a37e2a6215ae5631,
title = "In vitro percutaneous absorption and in vivo protoporphyrin IX accumulation in skin and tumors after topical 5-aminolevulinic acid application with enhancement using an erbium: YAG laser",
abstract = "5-Aminolevulinic acid (ALA) is used as a precursor of protoporphyrin IX (PpIX) for photodynamic therapy (PDT) of superficial skin cancers and subcutaneous metastases of internal malignancies. The permeability of ALA across intact skin is always low, making it difficult to achieve the desired therapeutic benefits. Hence new methods for enhancing ALA permeation are urgently needed. The aim of this study was to determine the in vivo kinetics of PpIX generation in mouse tissues after topical ALA application enhanced by an erbium (Er):yttrium-aluminum-garnet (YAG) laser. The in vitro permeation of ALA was also used to screen the optimal method for the in vivo study. The efficacy of the improved drug delivery was determined as a function of various laser fluences and cancer models. ALA applied to laser-treated skin produced a higher accumulations of PpIX within superficial skin and subcutaneous tumors as compared to those of the non-treated group (t-test, p <0.05). The enhancement ratios (ER) of laser-treated skin ranged from 1.7 to 4.9 times as compared to the control depending to the fluences used. The enhanced PpIX level of laser-treated skin was generally more pronounced in normal and lesional skin than in subcutaneous nodular tumors. Confocal laser scanning microscopy (CLSM) of laser-treated skin revealed intense red fluorescence within the epidermis and upper dermis, and a much-weaker fluorescence within the bottom layers of the skin. On the other hand, the fluorescence intensity of the control group was much lower than that of laser-treated group. The barrier properties of the skin irradiated by the laser had completely recovered within 3 days. Pretreatment of skin using an Er:YAG laser was useful in increasing the amount of Pp IX within skin tumors.",
keywords = "5-Aminolevulinic acid, Er:YAG laser, In vivo, Photodynamic therapy, Skin",
author = "Shen, {Shing Chuan} and Lee, {Woan Ruoh} and Fang, {Yi Ping} and Jun-Hung Hu and Fang, {Jia You}",
year = "2006",
month = "4",
doi = "10.1002/jps.20577",
language = "English",
volume = "95",
pages = "929--938",
journal = "Journal of Pharmaceutical Sciences",
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TY - JOUR

T1 - In vitro percutaneous absorption and in vivo protoporphyrin IX accumulation in skin and tumors after topical 5-aminolevulinic acid application with enhancement using an erbium

T2 - YAG laser

AU - Shen, Shing Chuan

AU - Lee, Woan Ruoh

AU - Fang, Yi Ping

AU - Hu, Jun-Hung

AU - Fang, Jia You

PY - 2006/4

Y1 - 2006/4

N2 - 5-Aminolevulinic acid (ALA) is used as a precursor of protoporphyrin IX (PpIX) for photodynamic therapy (PDT) of superficial skin cancers and subcutaneous metastases of internal malignancies. The permeability of ALA across intact skin is always low, making it difficult to achieve the desired therapeutic benefits. Hence new methods for enhancing ALA permeation are urgently needed. The aim of this study was to determine the in vivo kinetics of PpIX generation in mouse tissues after topical ALA application enhanced by an erbium (Er):yttrium-aluminum-garnet (YAG) laser. The in vitro permeation of ALA was also used to screen the optimal method for the in vivo study. The efficacy of the improved drug delivery was determined as a function of various laser fluences and cancer models. ALA applied to laser-treated skin produced a higher accumulations of PpIX within superficial skin and subcutaneous tumors as compared to those of the non-treated group (t-test, p <0.05). The enhancement ratios (ER) of laser-treated skin ranged from 1.7 to 4.9 times as compared to the control depending to the fluences used. The enhanced PpIX level of laser-treated skin was generally more pronounced in normal and lesional skin than in subcutaneous nodular tumors. Confocal laser scanning microscopy (CLSM) of laser-treated skin revealed intense red fluorescence within the epidermis and upper dermis, and a much-weaker fluorescence within the bottom layers of the skin. On the other hand, the fluorescence intensity of the control group was much lower than that of laser-treated group. The barrier properties of the skin irradiated by the laser had completely recovered within 3 days. Pretreatment of skin using an Er:YAG laser was useful in increasing the amount of Pp IX within skin tumors.

AB - 5-Aminolevulinic acid (ALA) is used as a precursor of protoporphyrin IX (PpIX) for photodynamic therapy (PDT) of superficial skin cancers and subcutaneous metastases of internal malignancies. The permeability of ALA across intact skin is always low, making it difficult to achieve the desired therapeutic benefits. Hence new methods for enhancing ALA permeation are urgently needed. The aim of this study was to determine the in vivo kinetics of PpIX generation in mouse tissues after topical ALA application enhanced by an erbium (Er):yttrium-aluminum-garnet (YAG) laser. The in vitro permeation of ALA was also used to screen the optimal method for the in vivo study. The efficacy of the improved drug delivery was determined as a function of various laser fluences and cancer models. ALA applied to laser-treated skin produced a higher accumulations of PpIX within superficial skin and subcutaneous tumors as compared to those of the non-treated group (t-test, p <0.05). The enhancement ratios (ER) of laser-treated skin ranged from 1.7 to 4.9 times as compared to the control depending to the fluences used. The enhanced PpIX level of laser-treated skin was generally more pronounced in normal and lesional skin than in subcutaneous nodular tumors. Confocal laser scanning microscopy (CLSM) of laser-treated skin revealed intense red fluorescence within the epidermis and upper dermis, and a much-weaker fluorescence within the bottom layers of the skin. On the other hand, the fluorescence intensity of the control group was much lower than that of laser-treated group. The barrier properties of the skin irradiated by the laser had completely recovered within 3 days. Pretreatment of skin using an Er:YAG laser was useful in increasing the amount of Pp IX within skin tumors.

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