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Liposome suppression of proliferative vitreoretinopathy. Rabbit model using antimetabolite encapsulated liposomes
K K Assil1, M Hartzer, R N Weinreb
1Bethesda Eye Institute, St. Louis University, Missouri 63110.
Abstract:
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.
Insights
Multivesicular liposomes effectively deliver 5-fluorouridine 5'-monophosphate (FUMP) to the vitreous, significantly reducing fibroproliferative membranes and retinal detachments in rabbit models of proliferative vitreoretinopathy.
Area of Science:
- Ophthalmology
- Pharmacology
- Biotechnology
Background:
- Proliferative vitreoretinopathy (PVR) is a major cause of vision loss after retinal detachment surgery.
- Fibroproliferative membranes in the vitreous contribute to tractional retinal detachments in PVR.
- Antimetabolites like cytarabine (Ara-C) and 5-fluorouridine 5'-monophosphate (FUMP) are potential treatments for PVR.
Purpose of the Study:
- To evaluate the efficacy of multivesicular liposome-encapsulated antimetabolites (FUMP and Ara-C) in preventing fibroproliferative membrane formation in a rabbit model.
- To assess the pharmacokinetic profile of liposome-encapsulated FUMP in the vitreous cavity.
Main Methods:
- Pharmacokinetic studies of FUMP half-life in rabbit vitreous after intravitreal liposome administration.
- Evaluation of liposome-encapsulated FUMP and Ara-C in a heterologous dermal fibroblast model of PVR in New Zealand white rabbits.
- Comparison of treatment groups with controls receiving liposomes without drug.
Main Results:
- Liposome-encapsulated FUMP demonstrated a significantly prolonged vitreous half-life (124 hr) compared to non-liposomal FUMP (4.5 hr).
- A single intravitreal injection of 0.1 mg liposome-encapsulated FUMP reduced tractional retinal detachments by 92% compared to controls.
- 1 mg of liposome-encapsulated Ara-C resulted in a 46% reduction in tractional detachments.
Conclusions:
- Multivesicular liposome-encapsulated FUMP shows significant potential for inhibiting fibroproliferative membrane formation in the vitreous.
- Liposomal encapsulation enhances drug delivery and efficacy for PVR treatment.
- Further investigation into liposome-encapsulated FUMP is warranted for clinical application in vitreoretinal surgery complications.