G G Giordano1, M F Refojo, M H Arroyo. 1. Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114.
Abstract
PURPOSE: The aims were to obtain a controlled intravitreous release of retinoic acid (RA) by injecting drug loaded microspheres of biodegradable polymers and to study the potential use of this RA delivery system in a rabbit model of proliferative vitreoretinopathy (PVR). METHODS: The release of RA in vitro from 15 mg of 50-50 poly(DL-lactide-co-glycolide) (PLGA) in 1 ml of water at room temperature was measured with a spectrophotometer. In a rabbit model of PVR, 11 eyes were injected with 5 mg of microspheres containing 22 micrograms of RA/mg of PLGA, and seven control eyes were injected with microspheres of the same polymer that did not contain RA. In a third group, six rabbits were injected with 5 mg (n = 3) and 10 mg (n = 3) of microspheres containing RA. RESULTS: The initial concentration of RA was 20.8 micrograms/mg of PLGA. The release curve showed a fairly constant daily release of 7 micrograms/d for about 30 days. At 40 days, the release rate decreased to about 6 micrograms/d. After 40 days, 82.8% of the RA was released. Four of 11 treated rabbits (36%) and 7/7 (100%) controls showed tractional retinal detachment (TRD) (P < 0.01) after 2 months. Histopathologically, a mild, localized, foreign body reaction was observed. CONCLUSIONS: The authors obtained a sustained release of RA from PLGA microspheres in vitro for 40 days. A single injection of RA-loaded microspheres in suspension in BSS was effective in reducing the incidence of TRD after 2 months in a rabbit model of PVR.
PURPOSE: The aims were to obtain a controlled intravitreous release of retinoic acid (RA) by injecting drug loaded microspheres of biodegradable polymers and to study the potential use of this RA delivery system in a rabbit model of proliferative vitreoretinopathy (PVR). METHODS: The release of RA in vitro from 15 mg of 50-50 poly(DL-lactide-co-glycolide) (PLGA) in 1 ml of water at room temperature was measured with a spectrophotometer. In a rabbit model of PVR, 11 eyes were injected with 5 mg of microspheres containing 22 micrograms of RA/mg of PLGA, and seven control eyes were injected with microspheres of the same polymer that did not contain RA. In a third group, six rabbits were injected with 5 mg (n = 3) and 10 mg (n = 3) of microspheres containing RA. RESULTS: The initial concentration of RA was 20.8 micrograms/mg of PLGA. The release curve showed a fairly constant daily release of 7 micrograms/d for about 30 days. At 40 days, the release rate decreased to about 6 micrograms/d. After 40 days, 82.8% of the RA was released. Four of 11 treated rabbits (36%) and 7/7 (100%) controls showed tractional retinal detachment (TRD) (P < 0.01) after 2 months. Histopathologically, a mild, localized, foreign body reaction was observed. CONCLUSIONS: The authors obtained a sustained release of RA from PLGA microspheres in vitro for 40 days. A single injection of RA-loaded microspheres in suspension in BSS was effective in reducing the incidence of TRD after 2 months in a rabbit model of PVR.
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