Efficiency of liposomal ATP in cerebral ischemia: bioavailability features.
This study was performed to elucidate the mechanism by which adenosine triphosphate (ATP) encapsulated into liposomes was able to protect against experimental brain ischemia in the rat. After intracarotidal administration of liposomally entrapped ATP, the ATP blood level increased dramatically whereas no change was observed after administration of free ATP. This suggested that liposomes may protect ATP from its degradation by endothelial ectonucleotidases. On the other hand, it was observed that after administration of liposomally entrapped carboxyfluorescein (CF) to ischemic rats, the distribution of the brain fluorescence under the form of numerous punctiform structures was completely different from the diffuse fluorescence obtained with free CF injections. These data suggest that under certain hypoxic conditions the blood-brain barrier is open allowing the liposomes to reach the cerebral parenchyma. The mechanism of brain uptake is, however, still unclear: endothelial tight junctions opening or endothelial transcytosis.
Chapat
S
S
Laboratoire de Biochimie Métabolique et Clinique Université Paris.
Frey
V
V
Claperon
N
N
Bouchaud
C
C
Puisieux
F
F
Couvreur
P
P
Rossignol
P
P
Delattre
J
J
D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002339:Carotid Arteries; D004337:Drug Carriers; D005452:Fluoresceins; D007269:Injections, Intra-Arterial; D008081:Liposomes; D008297:Male; D008856:Microscopy, Fluorescence; D051381:Rats; D011919:Rats, Inbred Strains
D004337:Drug Carriers; D005452:Fluoresceins; D008081:Liposomes; C045132:4-carboxyfluorescein; D000255:Adenosine Triphosphate