A delta 5-aminolevulinic acid (ALA) bioadhesive gel has been developed and evaluated in an in-vivo mouse model for photodynamic treatment of gastric cancer or Barrett's oesophagus. Four gels were tested: noveon AA-1, keltrol T, lutrol and blanose. An initial in-vitro study of gel adhesion showed that noveon and keltrol had longer polyethylene transit times than lutrol and blanose. In-vivo assays indicated that protoporphyrin IX was synthesized by gastric mucosa when ALA-noveon and ALA-lutrol were used (preferable results for noveon). Keltrol was eliminated from the study after these investigations. Only ALA-noveon gel was retained for studies of the relationship between ALA dose and fluorescence. Fluorescence measurements in-vivo showed that ALA concentration and application time had an influence on protoporphyrin IX synthesis. Maximum intensity (2091 counts s-1) was found with 2 mg mL-1 ALA, and fluorescence intensities differed with application time, reaching 1805 counts s-1 after 240 min. ALA-noveon, showing good adhesion and enabling efficient diffusion of ALA at a pH < 6, was considered the best formulation for maintaining ALA stability.
The purpose of this study was to develop an in vitro perfusion technique or "continuous-flow adhesion cell" model to predict the in vivo performances of different mucoadhesive drug delivery systems based on hydrogels. Two studies were performed, either using a rabbit small intestine or a polyethylene surface; the adhesion of four gels--two poly(acrylic acid)s (PAAs) (carbomer [CM] and polycarbophil [PC]), an ethyleneoxide-propyleneoxide block copolymer (Poloxamer 407 [PM]), and a polysaccharide (scleroglucane [SG])--were evaluated. In this respect, scleroglucane was used as a control. The adhesiveness of the different gels for both supports is in accordance with that described in the literature, that is, polycarbophil adhered more strongly than carbomer, which itself adhered more strongly than poloxamer. This study proved that the gels adhere more strongly to the polyethylene tube than to the rabbit small intestine, thus indicating that evidence for adhesion properties does not need any presence of mucus. Therefore, our in vitro model could be a good method, more precise and more simple than an ex vivo technique, to predict the bioadhesion of gelified devices.
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