Novel patch-based systems for the localised delivery of ALA-esters

Desmond I. J. Morrow, P. A. McCarron, A. David Woolfson, Petras Juzenas, Asta Juzeniene, Vladimir Iani, Johan Moan, Ryan F. Donnelly

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

In photodynamic therapy (PDT) a combination of visible light and a sensitising drug causes the destruction of selected cells. Aminolaevulinic acid (ALA) has been widely used in topical PDT for over 15 years. However, ALA does not possess favourable physicochemical properties for skin penetration. Consequently, the clearance rates for difficult to treat lesions, such as nodular basal cell carcinomas are relatively low. For the first time, equimolar concentrations of ALA, methyl-ALA (m-ALA) and hexyl-ALA (h-ALA) have been incorporated into a bioadhesive patch-based system. In vitro penetration studies into excised porcine skin revealed that ALA patches containing relatively high loadings (226.7 mu mol cm(-2)) were associated with significantly greater tissue concentrations (70.7 mu mol cm(-3)) than patches containing m-ALA (16.3 mu mol cm(-3)) or h-ALA (17.4 mu mol cm(-3)). ALA was also found to be the most efficient inducer of protoporphyrin (PpIX) fluorescence in mice, in vivo (maximum mean fluorescence: ALA = 236.2 a.u., m-ALA = 175.1 au., h-ALA = 193.5 a.u.). However, when the lipophilic hexylester was formulated in a pressure sensitive adhesive (PSA) patch, significantly higher PpIX levels were achieved compared to all bioadhesive systems tested. Of major importance, PSA patches containing relatively low h-ALA loadings induced high PpIX levels, which were localised to the application area. This study has highlighted the importance of rational selection of both the active agent and the delivery system. Bioadhesive preparations containing ALA are ideal for delivery to moist environments; whereas h-ALA-loaded PSA systems may facilitate enhanced delivery to dry areas of skin. In addition, owing to the relatively low loadings of h-ALA required in PSA patches, the costs of clinical PDT may potentially be reduced. (C) 2010 Elsevier B.V. All rights reserved.
LanguageEnglish
Pages59-69
JournalJOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
Volume101
Issue number1
DOIs
Publication statusPublished - Oct 2010

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aminolevulinic acid
esters
adhesives
fluorescence
therapeutics
protoporphyrin
carcinoma
physicochemical properties
cells
drugs
swine

Cite this

Morrow, Desmond I. J. ; McCarron, P. A. ; Woolfson, A. David ; Juzenas, Petras ; Juzeniene, Asta ; Iani, Vladimir ; Moan, Johan ; Donnelly, Ryan F. / Novel patch-based systems for the localised delivery of ALA-esters. In: JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY. 2010 ; Vol. 101, No. 1. pp. 59-69.
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title = "Novel patch-based systems for the localised delivery of ALA-esters",
abstract = "In photodynamic therapy (PDT) a combination of visible light and a sensitising drug causes the destruction of selected cells. Aminolaevulinic acid (ALA) has been widely used in topical PDT for over 15 years. However, ALA does not possess favourable physicochemical properties for skin penetration. Consequently, the clearance rates for difficult to treat lesions, such as nodular basal cell carcinomas are relatively low. For the first time, equimolar concentrations of ALA, methyl-ALA (m-ALA) and hexyl-ALA (h-ALA) have been incorporated into a bioadhesive patch-based system. In vitro penetration studies into excised porcine skin revealed that ALA patches containing relatively high loadings (226.7 mu mol cm(-2)) were associated with significantly greater tissue concentrations (70.7 mu mol cm(-3)) than patches containing m-ALA (16.3 mu mol cm(-3)) or h-ALA (17.4 mu mol cm(-3)). ALA was also found to be the most efficient inducer of protoporphyrin (PpIX) fluorescence in mice, in vivo (maximum mean fluorescence: ALA = 236.2 a.u., m-ALA = 175.1 au., h-ALA = 193.5 a.u.). However, when the lipophilic hexylester was formulated in a pressure sensitive adhesive (PSA) patch, significantly higher PpIX levels were achieved compared to all bioadhesive systems tested. Of major importance, PSA patches containing relatively low h-ALA loadings induced high PpIX levels, which were localised to the application area. This study has highlighted the importance of rational selection of both the active agent and the delivery system. Bioadhesive preparations containing ALA are ideal for delivery to moist environments; whereas h-ALA-loaded PSA systems may facilitate enhanced delivery to dry areas of skin. In addition, owing to the relatively low loadings of h-ALA required in PSA patches, the costs of clinical PDT may potentially be reduced. (C) 2010 Elsevier B.V. All rights reserved.",
author = "Morrow, {Desmond I. J.} and McCarron, {P. A.} and Woolfson, {A. David} and Petras Juzenas and Asta Juzeniene and Vladimir Iani and Johan Moan and Donnelly, {Ryan F.}",
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Morrow, DIJ, McCarron, PA, Woolfson, AD, Juzenas, P, Juzeniene, A, Iani, V, Moan, J & Donnelly, RF 2010, 'Novel patch-based systems for the localised delivery of ALA-esters', JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, vol. 101, no. 1, pp. 59-69. https://doi.org/10.1016/j.jphotobiol.2010.06.012

Novel patch-based systems for the localised delivery of ALA-esters. / Morrow, Desmond I. J.; McCarron, P. A.; Woolfson, A. David; Juzenas, Petras; Juzeniene, Asta; Iani, Vladimir; Moan, Johan; Donnelly, Ryan F.

In: JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, Vol. 101, No. 1, 10.2010, p. 59-69.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Novel patch-based systems for the localised delivery of ALA-esters

AU - Morrow, Desmond I. J.

AU - McCarron, P. A.

AU - Woolfson, A. David

AU - Juzenas, Petras

AU - Juzeniene, Asta

AU - Iani, Vladimir

AU - Moan, Johan

AU - Donnelly, Ryan F.

PY - 2010/10

Y1 - 2010/10

N2 - In photodynamic therapy (PDT) a combination of visible light and a sensitising drug causes the destruction of selected cells. Aminolaevulinic acid (ALA) has been widely used in topical PDT for over 15 years. However, ALA does not possess favourable physicochemical properties for skin penetration. Consequently, the clearance rates for difficult to treat lesions, such as nodular basal cell carcinomas are relatively low. For the first time, equimolar concentrations of ALA, methyl-ALA (m-ALA) and hexyl-ALA (h-ALA) have been incorporated into a bioadhesive patch-based system. In vitro penetration studies into excised porcine skin revealed that ALA patches containing relatively high loadings (226.7 mu mol cm(-2)) were associated with significantly greater tissue concentrations (70.7 mu mol cm(-3)) than patches containing m-ALA (16.3 mu mol cm(-3)) or h-ALA (17.4 mu mol cm(-3)). ALA was also found to be the most efficient inducer of protoporphyrin (PpIX) fluorescence in mice, in vivo (maximum mean fluorescence: ALA = 236.2 a.u., m-ALA = 175.1 au., h-ALA = 193.5 a.u.). However, when the lipophilic hexylester was formulated in a pressure sensitive adhesive (PSA) patch, significantly higher PpIX levels were achieved compared to all bioadhesive systems tested. Of major importance, PSA patches containing relatively low h-ALA loadings induced high PpIX levels, which were localised to the application area. This study has highlighted the importance of rational selection of both the active agent and the delivery system. Bioadhesive preparations containing ALA are ideal for delivery to moist environments; whereas h-ALA-loaded PSA systems may facilitate enhanced delivery to dry areas of skin. In addition, owing to the relatively low loadings of h-ALA required in PSA patches, the costs of clinical PDT may potentially be reduced. (C) 2010 Elsevier B.V. All rights reserved.

AB - In photodynamic therapy (PDT) a combination of visible light and a sensitising drug causes the destruction of selected cells. Aminolaevulinic acid (ALA) has been widely used in topical PDT for over 15 years. However, ALA does not possess favourable physicochemical properties for skin penetration. Consequently, the clearance rates for difficult to treat lesions, such as nodular basal cell carcinomas are relatively low. For the first time, equimolar concentrations of ALA, methyl-ALA (m-ALA) and hexyl-ALA (h-ALA) have been incorporated into a bioadhesive patch-based system. In vitro penetration studies into excised porcine skin revealed that ALA patches containing relatively high loadings (226.7 mu mol cm(-2)) were associated with significantly greater tissue concentrations (70.7 mu mol cm(-3)) than patches containing m-ALA (16.3 mu mol cm(-3)) or h-ALA (17.4 mu mol cm(-3)). ALA was also found to be the most efficient inducer of protoporphyrin (PpIX) fluorescence in mice, in vivo (maximum mean fluorescence: ALA = 236.2 a.u., m-ALA = 175.1 au., h-ALA = 193.5 a.u.). However, when the lipophilic hexylester was formulated in a pressure sensitive adhesive (PSA) patch, significantly higher PpIX levels were achieved compared to all bioadhesive systems tested. Of major importance, PSA patches containing relatively low h-ALA loadings induced high PpIX levels, which were localised to the application area. This study has highlighted the importance of rational selection of both the active agent and the delivery system. Bioadhesive preparations containing ALA are ideal for delivery to moist environments; whereas h-ALA-loaded PSA systems may facilitate enhanced delivery to dry areas of skin. In addition, owing to the relatively low loadings of h-ALA required in PSA patches, the costs of clinical PDT may potentially be reduced. (C) 2010 Elsevier B.V. All rights reserved.

U2 - 10.1016/j.jphotobiol.2010.06.012

DO - 10.1016/j.jphotobiol.2010.06.012

M3 - Article

VL - 101

SP - 59

EP - 69

JO - Journal of Photochemistry and Photobiology B: Biology

T2 - Journal of Photochemistry and Photobiology B: Biology

JF - Journal of Photochemistry and Photobiology B: Biology

SN - 1011-1344

IS - 1

ER -