The influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic sensitization

Casas, Adriana; Fukuda, Haydée; Venosa, Gabriela Di; Batlle, Alcira

doi:10.1111/j.1365-2133.2000.03711.x

Cited by 58 publications

(28 citation statements)

References 22 publications

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“…This is especially a problem in ALA-PDT. It is likely that poor response of BCCs, particularly nodular lesions to ALA-PDT, arises from an insufficient concentration of topical ALA achieved at approximately 2 mm from the surface of the lesion [24,44].…”

Section: Discussionmentioning

confidence: 99%

Photodynamic therapy of head and neck basal cell carcinoma according to different clinicopathologic features

et al. 2005

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Section: Discussionmentioning

confidence: 99%

Photodynamic therapy of head and neck basal cell carcinoma according to different clinicopathologic features

et al. 2005

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“…[4] Consequently, the penetration depth of ALA in intact skin is low, typically 1-2 mm. [5,6] Unsurprisingly, reports of ALA PDT for treatment of surface lesions describe long application times and formulations with high drug loadings. Times ranging from 2 to 6 h [7] and loadings of 10-30% (w/w) in a cream, ointment or gel formulation are commonplace.…”

Section: Introductionmentioning

confidence: 99%

Aminolevulinic acid-loaded Witepsol microparticles manufactured using a spray congealing procedure: implications for topical photodynamic therapy

Al-Kassas¹,

Donnelly²,

McCarron³

2009

j pharm pharmacol

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Objectives The aim was to enhance aminolevulinic acid (ALA) stability by incorporation into low-melting microparticles prepared using a spray congealing procedure and to evaluate temperature-triggered release, allowing topical bioavailability following melting at skin temperature. Methods ALA-loaded Witepsol microparticles were prepared using a novel spray congealing technique. Entrapment efficiency was compared with conventional emulsionbased methods and modelled drug release profiles determined using a membrane separation technique. Raised receiver medium temperature was used to determine triggered release. Bioavailability and lipid-mediated enhancement of ALA penetration were determined in excised murine skin. Key findings ALA-loaded Witepsol microparticles were spherical, with a mean diameter of 20 mm. Loading and stability studies demonstrated effective encapsulation, ranging from 91% to 100%, with no evidence of degradation to pyrazine derivatives. ALA release correlated with dissolution medium temperature, triggered at temperatures close to that of skin. Results suggested that molten Witepsol enhanced cutaneous permeation, whereas incorporation of microparticles in a semi-solid vehicle attenuated ALA penetration. Optimal use was direct application under occlusion. Conclusions Spray congealing is superior to the emulsion-based procedures with respect to encapsulation efficiency of ALA in Witepsol matrices, providing temperature-triggered release, enhanced stability and improved penetration of ALA through keratinised skin. These features could improve ALA delivery to superficial lesions as part of photodynamic therapy.

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“…It has been reported that DMSO can improve the accumulation of PpIX in cell lines (Malik et al, 1995). Employing ALA plus DMSO in vivo in a transplantable murine adenocarcinoma, Casas et al (2000) have found a higher porphyrin accumulation in the skin overlying the tumour tissue and in the first 2 mm of tumour.…”

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confidence: 91%

Topical application of ALA and ALA hexyl ester on a subcutaneous murine mammary adenocarcinoma: tissue distribution

et al. 2003

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Although 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) has proven to be clinically beneficial for the treatment of certain cancers, including a variety of skin cancers, optimal tissue localisation still remains a problem. An approach to improve the bioavailability of protoporphyrin IX (PpIX) is the use of ALA derivatives instead of ALA. In this work, we employed a subcutaneous murine mammary adenocarcinoma to study the tissue distribution pattern of the ALA hexyl ester (He-ALA) in comparison with ALA after their topical application in different vehicles. He-ALA induced porphyrin synthesis in the skin overlying the tumour (SOT), but it did not reach the tumour tissue as efficiently. Only 5 h after He-ALA lotion application, tumour porphyrin levels surpassed control values. He-ALA delivered in cream induced a substantially lower porphyrin synthesis in SOT, reinforcing the importance of the vehicle in the use of topical PDT. Porphyrin levels in internal organs remained almost within control values when He-ALA was employed. The addition of DMSO to ALA formulation slightly increased tumour and SOT porphyrin biosynthesis, but it did not when added to He-ALA lotion.

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The influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic sensitization

Abstract: These findings reinforce the importance of the vehicle in topical ALA-based PDT, and explain the mechanism of action of DMSO in enhancing protoporphyrin IX biosynthesis in superficial lesions.

Cited by 58 publications

References 22 publications

Photodynamic therapy of head and neck basal cell carcinoma according to different clinicopathologic features

Photodynamic therapy of head and neck basal cell carcinoma according to different clinicopathologic features

Aminolevulinic acid-loaded Witepsol microparticles manufactured using a spray congealing procedure: implications for topical photodynamic therapy

Topical application of ALA and ALA hexyl ester on a subcutaneous murine mammary adenocarcinoma: tissue distribution

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