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Adv Drug Deliv Rev. 2004 Jan 13;56(1):77-94.

Photodynamic therapy of skin cancer: controlled drug delivery of 5-ALA and its esters.

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  • 1Departamento de Ciências Farmacêuticas da Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.


Photodynamic therapy (PDT) is a tool for the treatment of certain cancerous and pre-cancerous conditions in dermatology. 5-Aminolevulinic acid (5-ALA) and simple derivatives thereof are the principal compounds used for this purpose. For optimal efficacy, the drug must be released at an appropriate rate from the formulation and penetrate the skin, ideally to reach the target tissue at a sufficiently high concentration. Because ALA is a polar, zwitterionic compound, its formulation in conventional topical vehicles, and its inherently poor skin permeability, poses important challenges for the pharmaceutical scientist. The synthesis of more lipophilic (e.g. ester) prodrugs of ALA resolves, in part, these issues but then demands that questions, related to biotransformation back to the parent 5-ALA and to stability, be addressed. The objective of this review, therefore, is to evaluate the state-of-the-art and identify those areas in which additional research is necessary.

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