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Oleic Acid as Optimizer of the Skin Delivery of 5-Aminolevulinic Acid in Photodynamic Therapy

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Purpose

In photodynamic therapy (PDT), topically applied aminolevulinic acid (5-ALA) is converted to protoporphyrin IX (PpIX), which upon light excitation induces tumor destruction. To optimize 5-ALA-PDT via improving the highly hydrophilic 5-ALA limited penetration into the skin, we propose the use of the known skin penetration enhancer, oleic acid (OA).

Methods

In vitro skin penetration and retention of 5-ALA (1% w/w) were measured in the presence or absence of OA (2.5, 5.0, and 10.0% w/w) in propylene glycol (PG) using porcine ear skin as the membrane. In vivo accumulation of PpIX, 4 h after application, was determined fluorometrically in healthy mice skin by chemical extracton of skin samples. In vivo PpIX fluorescence kinetics was also investigated by noninvasive techniques using an optical fiber probe, for 30 min up to 24 h after topical application of 1.0% 5-ALA + 10.0% OA in PG on hairless mice skins.

Results

The flux and in vitro retention of 5-ALA in viable epidermis increased in the presence of 10.0% (w/w) OA. The amounts of PpIX, evaluated both by chemical tissue extractions and in vivo measurements by an optical fiber probe, increased after applying 5-ALA formulations containing 5.0 or 10.0% OA. Moreover, in vivo kinetic studies showed an increase in skin PpIX accumulation when formulations containing 10% OA were used; PpIX accumulation was also maintained longer compared to controls.

Conclusions

Both in vitro and in vivo results show the OA potential as an optimizer of 5-ALA skin delivery.

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Acknowledgments

The authors would like to thank the Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Pesquisa (CNPq), Brazil, for supporting this study. M.B.R. Pierre was a recipient of a FAPESP fellowship.

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Authors and Affiliations

  1. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903, Ribeirão Preto, São Paulo, Brazil

    Maria Bernadete Riemma Pierre, Eduardo Ricci Jr & Maria Vitória Lopes Badra Bentley

  2. Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil

    Antonio Cláudio Tedesco

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  1. Maria Bernadete Riemma Pierre
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  2. Eduardo Ricci Jr
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  3. Antonio Cláudio Tedesco
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  4. Maria Vitória Lopes Badra Bentley
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Correspondence to Maria Vitória Lopes Badra Bentley.

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Pierre, M.B.R., Ricci, E., Tedesco, A.C. et al. Oleic Acid as Optimizer of the Skin Delivery of 5-Aminolevulinic Acid in Photodynamic Therapy. Pharm Res 23, 360–366 (2006). https://doi.org/10.1007/s11095-005-9261-x

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