In vivo photosensitizing efficiency of a diphenylchlorin sensitizer: interest of a DMPC liposome formulation.
The pharmacokinetic behaviour and phototherapeutic effectiveness of 2,3-dihydro-5,15-di(3,5-dihydroxyphenyl)porphyrin (SIM01), a new diphenylchlorin photosensitizer incorporated into dimyristoyl phosphatidylcholine (DMPC) liposomes, were studied in vivo in nude mice bearing HT29 human adenocarcinoma. The photophysical and photochemical specificity of SIM01 are a strong absorption at 647 nm, high photosensitizing efficiency and a rapid pharmacokinetic profile making SIM01 an attractive candidate for PDT. The pharmacokinetics in vivo, as determined by fiber spectrofluorimetry, showed that tumor concentration was found maximal for SIM01 and SIM01-DMPC 12h after injection, with better uptake for the liposomal formulation. With a 2 mg kg(-1) dye dose, optimal PDT response occurred when the interval between injection and irradiation was 12h for both formulations, with laser irradiation of 300J cm(-2) (650 nm, 300 mW). At day 12 after treatment involving a 12-h interval between injection and irradiation, tumor growth was decreased by 26% for SIM01 (P=0.005) and 35% for SIM01-DMPC (P=0.001) as compared to the untreated group.SIM01 would appear to be a powerful sensitizer characterized by high in vivo phototoxicity and rapid tissue uptake and elimination. Our results suggest that SIM01 delivered in a liposomal dispersion is as effective as the raw formulation, something that would open new delivery routes and PDT applications.
Bourré
Ludovic
L
Laboratoire de Photobiologie des Cancers, Département Laser, Neurochirurgie, CHU Nantes, 44480 Nantes, France.
Thibaut
Sonia
S
Fimiani
Monica
M
Ferrand
Yann
Y
Simonneaux
Gérard
G
Patrice
Thierry
T
D000818:Animals; D002626:Chemistry, Pharmaceutical; D004134:Dimyristoylphosphatidylcholine / Q000008:administration & dosage; D019073:HT29 Cells; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D008297:Male; D051379:Mice; D008819:Mice, Nude; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011166:Porphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013050:Spectrometry, Fluorescence
C481258:2,3-dihydro-5,15-bis(3,5-dihydroxyphenyl)porphyrin; D008081:Liposomes; D017319:Photosensitizing Agents; D011166:Porphyrins; D004134:Dimyristoylphosphatidylcholine