Potential efficacy of a delta 5-aminolevulinic acid bioadhesive gel formulation for the photodynamic treatment of lesions of the gastrointestinal tract in mice.
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.
Vonarx
V
V
Département Laser, Hôpital Nord Laennec, Nantes, France.
Eleouet
S
S
Carre
J
J
Ioss
P
P
Gouyette
A
A
Leray
A M
AM
Merle
C
C
Lajat
Y
Y
Patrice
T
T
D000622:Aminolevulinic Acid / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001471:Barrett Esophagus / Q000188:drug therapy* / Q000473:pathology; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D005336:Fiber Optic Technology; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D005782:Gels; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000378:metabolism; D011524:Protoporphyrins / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014014:Tissue Adhesives / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D001672:Biocompatible Materials; D005782:Gels; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D014014:Tissue Adhesives; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX