Potential efficacy of a delta 5-aminolevulinic acid thermosetting gel formulation for use in photodynamic therapy of lesions of the gastrointestinal tract

Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX may play a role in the treatment of dysplastic Barrett's oesophagus. An ALA thermosetting gel (Pluronic(R) F-127) was developed and evaluated in an in vivo mouse model for potential use in PDT of Barrett's mucosa. In vitro studies of the influence of Pluronic(R) F-127 percentage on thermosetting gel temperature, followed by the influence of ALA concentration on thermosetting temperature and ALA-gel stability as a function of time or temperature were studied. 112 vivo relationships between ALA doses and fluorescence were studied to determine the optimal concentration. Fluorescence measurement in vivo showed that ALA concentration and time had a nonlinear influence on protoporphyrin IX synthesis. For ALA-gel applications longer than 30 min a plateau fluorescence was reached, the maximum fluorescence being obtained after 4 h whatever the time of contact. The maximum intensity (2824 counts s(-1)) was found with 40 mg mL(-1) ALA-gel, and fluorescence intensities differed with time, reaching a maximum after 3-4 h. ALA-Pluronic F-127 is a suitable formulation for treatment of Barrett's oesophagus, allowing easy application in liquid form at 4degreesC and good adhesion in the oesophagus in gel form, with efficient diffusion of ALA into treated mucosa. (C) 2002 Elsevier Science Ltd.