Liposome suppression of proliferative vitreoretinopathy. Rabbit model using antimetabolite encapsulated liposomes.
The effects of the antimetabolites, cytarabine (Ara-C) and 5-fluorouridine 5'-monophosphate (FUMP), encapsulated in multivesicular liposomes on formation of vitreous fibroproliferative membranes in New Zealand white (NZW) rabbits were studied. In pharmacokinetic studies, the drug half-life in the vitreous cavity was 124 hr after intravitreal administration of 1.0 mg of FUMP in liposomes. By contrast, the drug half-life after a single injection in nonliposome-treated controls was only 4.5 hr. In a heterologous dermal fibroblast model of proliferative vitreoretinopathy (PVR), there was a 92% decrease in frequency of tractional retinal detachments in rabbits receiving a single intravitreal injection of liposome-encapsulated 0.1 mg of FUMP compared with controls receiving liposomes without drug. A dose of 1 mg of Ara-C in liposome-treated rabbits was associated with only a 46% reduction in tractional detachment compared with controls. Multivesicular liposome-encapsulated FUMP may be useful for inhibiting formation of fibroproliferative membranes in the vitreous after vitreoretinal surgery.
Bethesda Eye Institute, St. Louis University, Missouri 63110.
K K
KK
Assil
M
M
Hartzer
R N
RN
Weinreb
M
M
Nehorayan
T
T
Ward
M
M
Blumenkranz
D000818:Animals; D003561:Cytarabine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004337:Drug Carriers; D005128:Eye Diseases / Q000378:metabolism / Q000517:prevention & control; D006207:Half-Life; D008081:Liposomes; D011817:Rabbits; D012164:Retinal Diseases / Q000378:metabolism / Q000517:prevention & control*; D014500:Uracil Nucleotides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014822:Vitreous Body / Q000378:metabolism
D004337:Drug Carriers; D008081:Liposomes; D014500:Uracil Nucleotides; D003561:Cytarabine; C016462:5-fluorouridine 5'-phosphate