Influence of penetration enhancers on topical delivery of 5-aminolevulinic acid from bioadhesive patches

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

10 Citations (Scopus)

Abstract

Objectives The inclusion 01 chemical penetration enhancers in a novel patch-based system for the delivery of 5-aminolevulinic acid (ALA) was examined in vitro and in vivo. Poor penetration of ALA has been implicated as the primary factor for low response rates achieved with topical ALA-based photodynamic therapy of thicker neoplastic lesions. such as nodular basal cell carcinomas. Methods Several chemical permeation enhancers (dimethylsulfoxide, Labrafac CC. Labrafac PG and Labrafil M1944CS) were incorporated into bioadhesive patches tailored to deliver 19 mg ALA/cm(2). Key findings In-vitro depth penetration studies into excised porcine skin showed that high concentrations of ALA (>9 mu mol/cm(3)) could be delivered to a depth of 1.875 mm. However, inclusion of permeation enhancers did not significantly increase ALA delivery, relative to the control (P > 0.05). In-vivo studies were in strong agreement with in-vitro results, with formulations containing chemical enhancers showing no improvement in delivery compared with the control. Conclusions The patches designed in this work are suited to defineable ALA delivery without the need to immobilise patients for up to 6 h, as IS common with the cream-under-occlusion approach. Overall, permeation enhancers were not found to markedly enhance the topical delivery of ALA. 11 chemical penetration enhancers may have a greater effect on the delivery of more lipophilic ALA prodrugs, which are thought to primarily permeate the stratum corneum via the intercellular pathway.
LanguageEnglish
Pages685-695
JournalJOURNAL OF PHARMACY AND PHARMACOLOGY
Volume62
Issue number6, Sp.
DOIs
Publication statusPublished - Jun 2010

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Aminolevulinic Acid
Basal Cell Carcinoma
Photochemotherapy
Prodrugs
Dimethyl Sulfoxide
Cornea
Swine
Skin

Cite this

Morrow, Desmond I. J. ; McCarron, P. A. ; Woolfson, A. David ; Juzenas, Petras ; Juzeniene, Asta ; Iani, Vladimir ; Moan, Johan ; Donnelly, Ryan F. / Influence of penetration enhancers on topical delivery of 5-aminolevulinic acid from bioadhesive patches. In: JOURNAL OF PHARMACY AND PHARMACOLOGY. 2010 ; Vol. 62, No. 6, Sp. pp. 685-695.
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title = "Influence of penetration enhancers on topical delivery of 5-aminolevulinic acid from bioadhesive patches",
abstract = "Objectives The inclusion 01 chemical penetration enhancers in a novel patch-based system for the delivery of 5-aminolevulinic acid (ALA) was examined in vitro and in vivo. Poor penetration of ALA has been implicated as the primary factor for low response rates achieved with topical ALA-based photodynamic therapy of thicker neoplastic lesions. such as nodular basal cell carcinomas. Methods Several chemical permeation enhancers (dimethylsulfoxide, Labrafac CC. Labrafac PG and Labrafil M1944CS) were incorporated into bioadhesive patches tailored to deliver 19 mg ALA/cm(2). Key findings In-vitro depth penetration studies into excised porcine skin showed that high concentrations of ALA (>9 mu mol/cm(3)) could be delivered to a depth of 1.875 mm. However, inclusion of permeation enhancers did not significantly increase ALA delivery, relative to the control (P > 0.05). In-vivo studies were in strong agreement with in-vitro results, with formulations containing chemical enhancers showing no improvement in delivery compared with the control. Conclusions The patches designed in this work are suited to defineable ALA delivery without the need to immobilise patients for up to 6 h, as IS common with the cream-under-occlusion approach. Overall, permeation enhancers were not found to markedly enhance the topical delivery of ALA. 11 chemical penetration enhancers may have a greater effect on the delivery of more lipophilic ALA prodrugs, which are thought to primarily permeate the stratum corneum via the intercellular pathway.",
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, 'Influence of penetration enhancers on topical delivery of 5-aminolevulinic acid from bioadhesive patches', JOURNAL OF PHARMACY AND PHARMACOLOGY, vol. 62, no. 6, Sp., pp. 685-695. https://doi.org/10.1211/jpp/62.06.0004

Influence of penetration enhancers on topical delivery of 5-aminolevulinic acid from bioadhesive patches. / Morrow, Desmond I. J.; McCarron, P. A.; Woolfson, A. David; Juzenas, Petras; Juzeniene, Asta; Iani, Vladimir; Moan, Johan; Donnelly, Ryan F.

In: JOURNAL OF PHARMACY AND PHARMACOLOGY, Vol. 62, No. 6, Sp., 06.2010, p. 685-695.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Influence of penetration enhancers on topical delivery of 5-aminolevulinic acid from bioadhesive patches

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 - 2010/6

Y1 - 2010/6

N2 - Objectives The inclusion 01 chemical penetration enhancers in a novel patch-based system for the delivery of 5-aminolevulinic acid (ALA) was examined in vitro and in vivo. Poor penetration of ALA has been implicated as the primary factor for low response rates achieved with topical ALA-based photodynamic therapy of thicker neoplastic lesions. such as nodular basal cell carcinomas. Methods Several chemical permeation enhancers (dimethylsulfoxide, Labrafac CC. Labrafac PG and Labrafil M1944CS) were incorporated into bioadhesive patches tailored to deliver 19 mg ALA/cm(2). Key findings In-vitro depth penetration studies into excised porcine skin showed that high concentrations of ALA (>9 mu mol/cm(3)) could be delivered to a depth of 1.875 mm. However, inclusion of permeation enhancers did not significantly increase ALA delivery, relative to the control (P > 0.05). In-vivo studies were in strong agreement with in-vitro results, with formulations containing chemical enhancers showing no improvement in delivery compared with the control. Conclusions The patches designed in this work are suited to defineable ALA delivery without the need to immobilise patients for up to 6 h, as IS common with the cream-under-occlusion approach. Overall, permeation enhancers were not found to markedly enhance the topical delivery of ALA. 11 chemical penetration enhancers may have a greater effect on the delivery of more lipophilic ALA prodrugs, which are thought to primarily permeate the stratum corneum via the intercellular pathway.

AB - Objectives The inclusion 01 chemical penetration enhancers in a novel patch-based system for the delivery of 5-aminolevulinic acid (ALA) was examined in vitro and in vivo. Poor penetration of ALA has been implicated as the primary factor for low response rates achieved with topical ALA-based photodynamic therapy of thicker neoplastic lesions. such as nodular basal cell carcinomas. Methods Several chemical permeation enhancers (dimethylsulfoxide, Labrafac CC. Labrafac PG and Labrafil M1944CS) were incorporated into bioadhesive patches tailored to deliver 19 mg ALA/cm(2). Key findings In-vitro depth penetration studies into excised porcine skin showed that high concentrations of ALA (>9 mu mol/cm(3)) could be delivered to a depth of 1.875 mm. However, inclusion of permeation enhancers did not significantly increase ALA delivery, relative to the control (P > 0.05). In-vivo studies were in strong agreement with in-vitro results, with formulations containing chemical enhancers showing no improvement in delivery compared with the control. Conclusions The patches designed in this work are suited to defineable ALA delivery without the need to immobilise patients for up to 6 h, as IS common with the cream-under-occlusion approach. Overall, permeation enhancers were not found to markedly enhance the topical delivery of ALA. 11 chemical penetration enhancers may have a greater effect on the delivery of more lipophilic ALA prodrugs, which are thought to primarily permeate the stratum corneum via the intercellular pathway.

U2 - 10.1211/jpp/62.06.0004

DO - 10.1211/jpp/62.06.0004

M3 - Article

VL - 62

SP - 685

EP - 695

JO - Journal of Pharmacy and Pharmacology

T2 - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

IS - 6, Sp.

ER -