Photothrombic activity of m-THPC-loaded liposomal formulations: pre-clinical assessment on chick chorioallantoic membrane model.
The objective of this study was to evaluate the ability of meso-tetra(hydroxyphenyl)chlorin (m-THPC) encapsulated into liposomal formulations to occlude neovascularization. Two m-THPC formulations including conventional or plain liposomes (Foslip) based on dipalmitoylphosphatidylcholine (DPPC) and the corresponding long-circulating poly(ethylene glycol) (PEG)-modified liposomes (PEGylated liposomes: Fospeg) were evaluated as delivery systems. Using the chick chorioallantoic membrane (CAM) as in vivo model, the fluorescence pharmacokinetic behaviour of encapsulated m-THPC reflecting the rate of the extravasation of the dye from the CAM vasculature and its photothrombic effectiveness were determined. This study was focused on the influence of the drug and/or light doses on the mean retention time of m-THPC within the CAM blood vessels after intravenous injection, and its photothrombic efficacy. Irrespective of the formulations tested and the drug doses injected, similar fluorescence pharmacokinetic profiles were obtained. The fluorescence contrast reached a steady state 30 s after injection. Constant positive values of the fluorescence contrast suggest that m-THPC is confined into the intravascular compartment during the experimental time (500 s). However, the photodynamic therapy assays showed that Foslip appears to be less potent than Fospeg in terms of photothrombic activities on the CAM model. For instance, the light dose necessary to induce the desired vascular damage with Foslip was twice (100 J/cm2) higher than with Fospeg (50 J/cm2). It can be inferred that this pre-clinical study showed that the formulation based on PEGylated liposomes technology offers a suitable delivery system for the treatment of choroidal neovascularization associated with age-related macular degeneration.
Pegaz
B
B
Ecole Polytechnique Fédérale de Lausanne, EPFL-ENAC_LPAS, Station 6, CH-1015 Lausanne, Switzerland.
Debefve
E
E
Ballini
J-P
JP
Wagnières
G
G
Spaniol
S
S
Albrecht
V
V
Scheglmann
D V
DV
Nifantiev
N E
NE
van den Bergh
H
H
Konan-Kouakou
Y N
YN
D015060:1,2-Dipalmitoylphosphatidylcholine; D000465:Algorithms; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply / Q000187:drug effects*; D005079:Excipients; D007275:Injections, Intravenous; D008081:Liposomes; D008566:Membranes / Q000737:chemistry; D008652:Mesoporphyrins / Q000008:administration & dosage* / Q000494:pharmacology*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D013050:Spectrometry, Fluorescence
D005079:Excipients; D008081:Liposomes; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D015060:1,2-Dipalmitoylphosphatidylcholine; C072269:temoporfin