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Dendrimers as topical drug delivery systems for ALA and PpIX in the photodynamic therapy of skin cancer

Grant number: 06/03575-0
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2006
Effective date (End): November 30, 2010
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Renata Fonseca Vianna Lopez
Grantee:Luciana Mattoso Pires de Campos Araújo
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


The Photodynamic Therapy (PDT) is an innovative therapeutically modality for the treatment of skin cancer. The research in this area is directed to the study of photosensitisers and their precursors, as well as of drug delivery systems that optimize drug penetration and localization in the target tissue. The aminolevulinic acid (ALA), precursor of the photosensible protoporphyrin (PpIX), is the most used substance in topical PDT. However, its local bioavailability is normally insufficient to produce a complete therapeutic effect. Moreover, the stability of ALA in common formulations (solution and cream) is low, therefore the powder of the drug is mixed with other excipients only before use. In attempt to improve ALA stability and to increase the number of molecules available for the conversion in PpIX, the objective of this project is to prepare and to characterize dendrimers contain ALA and to study the passive and iontophoretic cutaneous absorption, in vitro and in vivo, of this substance from developed dendrimers. Moreover, as ALA is only the precursor of the photosensitising agent PpIX, which has not been used for topical delivery because of its high lipophilicity and diffusible subcellular localization, it is also claimed to obtain and to characterize, for the topical administration, dendrimers with PpIX. Dendrimers, in the same way of ciclodextrins, can form complexes with ALA or PpIX, increasing its stability and solubility in water. However, as dendrimers are macromolecules, they probably will not cross the skin passively. Thus, the formulations will be submitted to application of a weak electric current (iontophoresis). Iontophoresis must facilitate the penetration of the complex in the skin and, once into the tissue, this system can facilitate the entrance of the ALA and PpIX in the nucleus of the cells and improves its distribution in the tissue. (AU)

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
ARAÚJO, Luciana Mattoso Pires de Campos. Dendrimers as drug carriers for protoporphyrin IX to topical photodynamic therapy of skin cancer.. 2011. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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Filed patent(s) as a result of this research project

COMPLEXO DENDRÍMETRO-SUBSTÂNCIA FOTOSSENSIBILIZANTE, COMPOSIÇÃO COMPREENDENDO O REFERIDO COMPLEXO, USO DO COMPLEXO E KIT BR1020120024942 - Universidade de São Paulo (USP) . Danielle C. A. S. de Santana ; Flavio da Silva Emery ; Luciana M. P. de Campos Araújo ; Renata Fonseca Vianna Lopez ; Stephania Fleury Taveira - February 2012, 03